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1
Maysinger, Dusica, Mélanie Lalancette-Hébert, Jeff Ji, Katherine Jabbour, Jens Dernedde, Kim Silberreis, Rainer Haag, and Jasna Kriz. "Dendritic polyglycerols are modulators of microglia-astrocyte crosstalk." Future Neurology 14, no. 4 (November 2019): FNL31. http://dx.doi.org/10.2217/fnl-2019-0008.
Повний текст джерелаАнотація:
Aim: To determine the ability of sulfated dendritic polyglycerols (dPGS) to modulate neuroglia activation challenged with lipopolysaccharide (LPS). Materials & methods: Microglia/astrocyte activation in vivo was determined in transgenic animals expressing TLR2-/GFAP-luciferase reporter. Mechanisms implicated in microglia-astrocyte crosstalk were studied in primary mouse brain cultures. Results & discussion: dPGS significantly reduced microglia activation in vivo, and decreased astrocytic LCN2 production. Activated microglia are necessary for astrocyte stimulation and increase in LCN2 abundance. LCN2 production in astrocytes involves signaling via toll-like receptor 4, activation of NF-κB, IL6 and enhancement of reactive oxygen species. Conclusion: dPGS are powerful modulators of microglia-astrocyte crosstalk and LCN2 abundance; dPGS are promising anti-inflammatory dendritic nanostructures.
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Lalo, Ulyana, and Yuriy Pankratov. "Astrocytes as Perspective Targets of Exercise- and Caloric Restriction‐Mimetics." Neurochemical Research 46, no. 10 (March 7, 2021): 2746–59. http://dx.doi.org/10.1007/s11064-021-03277-2.
Повний текст джерелаАнотація:
AbstractEnhanced mental and physical activity can have positive effects on the function of aging brain, both in the experimental animals and human patients, although cellular mechanisms underlying these effects are currently unclear. There is a growing evidence that pre-clinical stage of many neurodegenerative diseases involves changes in interactions between astrocytes and neurons. Conversely, astrocytes are strategically positioned to mediate the positive influence of physical activity and diet on neuronal function. Thus, development of therapeutic agents which could improve the astroglia-neuron communications in ageing brain is of crucial importance. Recent advances in studies of cellular mechanisms of brain longevity suggest that astrocyte-neuron communications have a vital role in the beneficial effects of caloric restriction, physical exercise and their pharmacological mimetics on synaptic homeostasis and cognitive function. In particular, our recent data indicate that noradrenaline uptake inhibitor atomoxetine can enhance astrocytic Ca2+-signaling and astroglia-driven modulation of synaptic plasticity. Similar effects were exhibited by caloric restriction-mimetics metformin and resveratrol. The emerged data also suggest that astrocytes could be involved in the modulatory action of caloric restriction and its mimetics on neuronal autophagy. Still, the efficiency of astrocyte-targeting compounds in preventing age-related cognitive decline is yet to be fully explored, in particular in the animal models of neurodegenerative diseases and autophagy impairment.
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Allnoch, Baumgärtner, and Hansmann. "Impact of Astrocyte Depletion upon Inflammation and Demyelination in a Murine Animal Model of Multiple Sclerosis." International Journal of Molecular Sciences 20, no. 16 (August 12, 2019): 3922. http://dx.doi.org/10.3390/ijms20163922.
Повний текст джерелаАнотація:
Astrocytes play a key role in demyelinating diseases, like multiple sclerosis (MS), although many of their functions remain unknown. The aim of this study was to investigate the impact of astrocyte depletion upon de- and remyelination, inflammation, axonal damage, and virus distribution in Theiler`s murine encephalomyelitis (TME). Groups of two to six glial fibrillary acidic protein (GFAP)-thymidine-kinase transgenic SJL mice and SJL wildtype mice were infected with TME virus (TMEV) or mock (vehicle only). Astrocyte depletion was induced by the intraperitoneal administration of ganciclovir during the early and late phase of TME. The animals were clinically investigated while using a scoring system and a rotarod performance test. Necropsies were performed at 46 and 77 days post infection. Cervical and thoracic spinal cord segments were investigated using hematoxylin and eosin (H&E), luxol fast blue-cresyl violet (LFB), immunohistochemistry targeting Amigo2, aquaporin 4, CD3, CD34, GFAP, ionized calcium-binding adapter molecule 1 (Iba1), myelin basic protein (MBP), non-phosphorylated neurofilaments (np-NF), periaxin, S100A10, TMEV, and immunoelectron microscopy. The astrocyte depleted mice showed a deterioration of clinical signs, a downregulation and disorganization of aquaporin 4 in perivascular astrocytes accompanied by vascular leakage. Furthermore, astrocyte depleted mice showed reduced inflammation and lower numbers of TMEV positive cells in the spinal cord. The present study indicates that astrocyte depletion in virus triggered CNS diseases contributes to a deterioration of clinical signs that are mediated by a dysfunction of perivascular astrocytes.
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Chrishtop, V. V., T. A. Rumyantseva, and D. A. Pozhilov. "GFAP Expression in the Cerebral Cortex during the Development of Cerebral Hypoxia in Rats Showing Different Results in the Morris Water Maze." Journal Biomed 16, no. 1 (February 28, 2020): 89–98. http://dx.doi.org/10.33647/2074-5982-16-1-89-98.
Повний текст джерелаАнотація:
The state of cognitive functions in cerebrovascular disorders is one of the most urgent healthcare problems. Recently obtained data convincingly indicate the participation of astrocytes in the formation of cognitive functions of the brain. We conducted a study on 88 Wistar rats. Following the results of testing the rats in a Morris water maze, all animals were divided into two subgroups: those with a high (HLA) and low (LLA) level of spatial situational learning abilities in the Morris water maze test. The animals in the experimental group (48 animals) underwent bilateral ligation of both carotid arteries. The animals were removed from the experiment on the 21st, 60th and 90th day after the operation. Glial fibrillar acidic protein (GFAP), a marker of mature astrocytes, was detected using primary polyclonal rabbit antibodies on histological sections of the precentral gyrus of the brain. Data were obtained on a more pronounced decrease in the numerical density of astrocyte bodies and the number of astrocyte main processes in HLA and LLA animals in earlier (on the 21st day) and later (on the 90th day) stages of the experiment, respectively. The growth of the area occupied by the astrocyte processes occurred earlier in HLA animals (on the 60th day after the simulation) compared to LLA animals (on the 90th day after the simulation). The conducted factor analysis confirmed the presence of two factors associated with the dynamics of the studied parameters. The conclusion is made about alternative variants of changes in the studied groups. The HLA subgroup predominantly demonstrated changes of an alterational character in earlier experimental stages, while adaptive changes were observed in the later stages of the experiment. Conversely, in the LLA subgroup, alterations and adaptations occurred in later and earlier experimental stages, respectively.
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Hofmann, Gabrielle C., Eileen M. Hasser, and David D. Kline. "Unilateral vagotomy alters astrocyte and microglial morphology in the nucleus tractus solitarii of the rat." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 320, no. 6 (June 1, 2021): R945—R959. http://dx.doi.org/10.1152/ajpregu.00019.2021.
Повний текст джерелаАнотація:
The nucleus tractus solitarii (nTS) is the initial site of integration of sensory information from the cardiorespiratory system and contributes to reflex responses to hypoxia. Afferent fibers of the bilateral vagus nerves carry input from the heart, lungs, and other organs to the nTS where it is processed and modulated. Vagal afferents and nTS neurons are integrally associated with astrocytes and microglia that contribute to neuronal activity and influence cardiorespiratory control. We hypothesized that vagotomy would alter glial morphology and cardiorespiratory responses to hypoxia. Unilateral vagotomy (or sham surgery) was performed in rats. Prior to and seven days after surgery, baseline and hypoxic cardiorespiratory responses were monitored in conscious and anesthetized animals. The brainstem was sectioned and caudal, mid-area postrema (mid-AP), and rostral sections of the nTS were prepared for immunohistochemistry. Vagotomy increased immunoreactivity (-IR) of astrocytic glial fibrillary acidic protein (GFAP), specifically at mid-AP in the nTS. Similar results were found in the dorsal motor nucleus of the vagus (DMX). Vagotomy did not alter nTS astrocyte number, yet increased astrocyte branching and altered morphology. In addition, vagotomy both increased nTS microglia number and produced morphologic changes indicative of activation. Cardiorespiratory baseline parameters and hypoxic responses remained largely unchanged, but vagotomized animals displayed fewer augmented breaths (sighs) in response to hypoxia. Altogether, vagotomy alters nTS glial morphology, indicative of functional changes in astrocytes and microglia that may affect cardiorespiratory function in health and disease.
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Ramadasan-Nair, Renjini, Jessica Hui, Leslie S. Itsara, Philip G. Morgan, and Margaret M. Sedensky. "Mitochondrial Function in Astrocytes Is Essential for Normal Emergence from Anesthesia in Mice." Anesthesiology 130, no. 3 (March 1, 2019): 423–34. http://dx.doi.org/10.1097/aln.0000000000002528.
Повний текст джерелаАнотація:
Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background In mice, restriction of loss of the mitochondrial complex I gene Ndufs4 to glutamatergic neurons confers a profound hypersensitivity to volatile anesthetics similar to that seen with global genetic knockout of Ndufs4. Astrocytes are crucial to glutamatergic synapse functioning during excitatory transmission. Therefore, the authors examined the role of astrocytes in the anesthetic hypersensitivity of Ndufs4(KO). Methods A tamoxifen-activated astrocyte-specific Ndufs4(KO) mouse was constructed. The specificity of the astrocyte-specific inducible model was confirmed by using the green fluorescent protein reporter line Ai6. Approximately 120 astrocyte-specific knockout and control mice were used for the experiments. Mice were anesthetized with varying concentrations of isoflurane or halothane; loss of righting reflex and response to a tail clamp were determined and quantified as the induction and emergence EC50s. Because norepinephrine has been implicated in emergence from anesthesia and astrocytes respond to norepinephrine to release gliotransmitters, the authors measured norepinephrine levels in the brains of control and knockout Ndufs4 animals. Results The induction EC50s for tail clamp in both isoflurane and halothane were similar between the control and astrocyte-specific Ndufs4(KO) mice at 3 weeks after 4-hydroxy tamoxifen injection (induction concentration, EC50(ind)—isoflurane: control = 1.27 ± 0.12, astrocyte-specific knockout = 1.21 ± 0.18, P = 0.495; halothane: control = 1.28 ± 0.05, astrocyte-specific knockout = 1.20 ± 0.05, P = 0.017). However, the emergent concentrations in both anesthetics for the astrocyte-specific Ndufs4(KO) mice were less than the controls for tail clamp; (emergence concentration, EC50(em)—isoflurane: control = 1.18 ± 0.10, astrocyte-specific knockout = 0.67 ± 0.11, P < 0.0001; halothane: control = 1.08 ± 0.09, astrocyte-specific knockout = 0.59 ± 0.12, P < 0.0001). The induction EC50s for loss of righting reflex were also similar between the control and astrocyte-specific Ndufs4(KO) mice (EC50(ind)—isoflurane: control = 1.02 ± 0.10, astrocyte-specific knockout = 0.97 ± 0.06, P = 0.264; halothane: control = 1.03 ± 0.05, astrocyte-specific knockout = 0.99 ± 0.08, P = 0.207). The emergent concentrations for loss of righting reflex in both anesthetics for the astrocyte-specific Ndufs4(KO) mice were less than the control (EC50(em)—isoflurane: control = 1.0 ± 0.07, astrocyte-specific knockout = 0.62 ± 0.12, P < 0.0001; halothane: control = 1.0 ± 0.04, astrocyte-specific KO = 0.64 ± 0.09, P < 0.0001); N ≥ 6 for control and astrocyte-specific Ndufs4(KO) mice. For all tests, similar results were seen at 7 weeks after 4-hydroxy tamoxifen injection. The total norepinephrine content of the brain in global or astrocyte-specific Ndufs4(KO) mice was unchanged compared to control mice. Conclusions The only phenotype of the astrocyte-specific Ndufs4(KO) mouse was a specific impairment in emergence from volatile anesthetic-induced general anesthesia. The authors conclude that normal mitochondrial function within astrocytes is essential for emergence from anesthesia.
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Meldolesi, Jacopo. "Astrocytes: News about Brain Health and Diseases." Biomedicines 8, no. 10 (October 6, 2020): 394. http://dx.doi.org/10.3390/biomedicines8100394.
Повний текст джерелаАнотація:
Astrocytes, the most numerous glial cells in the brains of humans and other mammalian animals, have been studied since their discovery over 100 years ago. For many decades, however, astrocytes were believed to operate as a glue, providing only mechanical and metabolic support to adjacent neurons. Starting from a “revolution” initiated about 25 years ago, numerous astrocyte functions have been reconsidered, some previously unknown, others attributed to neurons or other cell types. The knowledge of astrocytes has been continuously growing during the last few years. Based on these considerations, in the present review, different from single or general overviews, focused on six astrocyte functions, chosen due in their relevance in both brain physiology and pathology. Astrocytes, previously believed to be homogeneous, are now recognized to be heterogeneous, composed by types distinct in structure, distribution, and function; their cooperation with microglia is known to govern local neuroinflammation and brain restoration upon traumatic injuries; and astrocyte senescence is relevant for the development of both health and diseases. Knowledge regarding the role of astrocytes in tauopathies and Alzheimer’s disease has grow considerably. The multiple properties emphasized here, relevant for the present state of astrocytes, will be further developed by ongoing and future studies.
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Babaee, Abdolreza, Seyed Hassan Eftekhar Vaghefi, Samereh Dehghani Soltani, Majid Asadi Shekaari, Nader Shahrokhi, and Mohsen Basiri. "Hippocampal Astrocyte Response to Melatonin Following Neural Damage Induction in Rats." Basic and Clinical Neuroscience Journal 12, no. 2 (March 1, 2021): 177–86. http://dx.doi.org/10.32598/bcn.12.2.986.1.
Повний текст джерелаАнотація:
Introduction: Brain injury induces an almost immediate response from glial cells, especially astrocytes. Activation of astrocytes leads to the production of inflammatory cytokines and reactive oxygen species that may result in secondary neuronal damage. Melatonin is an anti-inflammatory and antioxidant agent, and it has been reported to exert neuroprotection through the prevention of neuronal death in several models of central nervous system injury. This study aimed to investigate the effect of melatonin on astrocyte activation induced by Traumatic Brain Injury (TBI) in rat hippocampus and dentate gyrus. Methods: Animals were randomly divided into 5 groups; Sham group, TBI group, vehicle group, and melatonin‐treated TBI groups (TBI+Mel5, TBI+Mel20). Immunohistochemical method (GFAP marker) and TUNEL assay were used to evaluate astrocyte reactivity and neuronal death, respectively. Results: The results demonstrated that the astrocyte number was reduced significantly in melatonin‐treated groups compared to the vehicle group. Additionally, based on TUNEL results, melatonin administration noticeably reduced the number of apoptotic neurons in the rat hippocampus and dentate gyrus. Conclusion: In general, our findings suggest that melatonin treatment after brain injury reduces astrocyte reactivity as well as neuronal cell apoptosis in rat hippocampus and dentate gyrus.
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Rutka, James T., Masaji Murakami, Peter B. Dirks, Sherri Lynn Hubbard, Laurence E. Becker, Kozo Fukuyama, Shin Jung, and Kazuhito Matsuzawa. "Role of glial filaments in cells and tumors of glial origin: a review." Neurosurgical Focus 3, no. 1 (July 1997): E2. http://dx.doi.org/10.3171/foc.1997.3.1.2.
Повний текст джерелаАнотація:
In the adult human brain, normal astrocytes constitute nearly 40% of the total central nervous system (CNS) cell population and may assume a star-shaped configuration resembling epithelial cells insofar as the astrocytes remain intimately associated, through their cytoplasmic extensions, with the basement membrane of the capillary endothelial cells and the basal lamina of the glial limitans externa. Although their exact function remains unknown, in the past, astrocytes were thought to subserve an important supportive role for neurons, providing a favorable ionic environment, modulating extracellular levels of neurotransmitters, and serving as spacers that organize neurons. In immunohistochemical preparations, normal, reactive, and neoplastic astrocytes may be positively identified and distinguished from other CNS cell types by the expression of the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). This GFAP is a 50-kD intracytoplasmic filamentous protein that constitutes a portion of, and is specific for, the cytoskeleton of the astrocyte. This protein has proved to be the most specific marker for cells of astrocytic origin under normal and pathological conditions. Interestingly, with increasing astrocytic malignancy, there is progressive loss of GFAP production. As the human gene for GFAP has now been cloned and sequenced, this review begins with a summary of the molecular biology of GFAP including the proven utility of the GFAP promoter in targeting genes of interest to the CNS in transgenic animals. Based on the data provided the authors argue cogently for an expanded role of GFAP in complex cellular events such as cytoskeletal reorganization, maintenance of myelination, cell adhesion, and signaling pathways. As such, GFAP may not represent a mere mechanical integrator of cellular space, as has been previously thought. Rather, GFAP may provide docking sites for important kinases that recognize key cellular substrates that enable GFAP to form a dynamic continuum with microfilaments, integrin receptors, and the extracellular matrix.
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Rutka, James T., Masaji Murakami, Peter B. Dirks, Sherri Lynn Hubbard, Laurence E. Becker, Kozo Fukuyama, Shin Jung, Atsushi Tsugu, and Kazuhito Matsuzawa. "Role of glial filaments in cells and tumors of glial origin: a review." Journal of Neurosurgery 87, no. 3 (September 1997): 420–30. http://dx.doi.org/10.3171/jns.1997.87.3.0420.
Повний текст джерелаАнотація:
✓ In the adult human brain, normal astrocytes constitute nearly 40% of the total central nervous system (CNS) cell population and may assume a star-shaped configuration resembling epithelial cells insofar as the astrocytes remain intimately associated, through their cytoplasmic extensions, with the basement membrane of the capillary endothelial cells and the basal lamina of the glial limitans externa. Although their exact function remains unknown, in the past, astrocytes were thought to subserve an important supportive role for neurons, providing a favorable ionic environment, modulating extracellular levels of neurotransmitters, and serving as spacers that organize neurons. In immunohistochemical preparations, normal, reactive, and neoplastic astrocytes may be positively identified and distinguished from other CNS cell types by the expression of the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). Glial fibrillary acidic protein is a 50-kD intracytoplasmic filamentous protein that constitutes a portion of, and is specific for, the cytoskeleton of the astrocyte. This protein has proved to be the most specific marker for cells of astrocytic origin under normal and pathological conditions. Interestingly, with increasing astrocytic malignancy, there is progressive loss of GFAP production. As the human gene for GFAP has now been cloned and sequenced, this review begins with a summary of the molecular biology of GFAP including the proven utility of the GFAP promoter in targeting genes of interest to the CNS in transgenic animals. Based on the data provided the authors argue cogently for an expanded role of GFAP in complex cellular events such as cytoskeletal reorganization, maintenance of myelination, cell adhesion, and signaling pathways. As such, GFAP may not represent a mere mechanical integrator of cellular space, as has been previously thought. Rather, GFAP may provide docking sites for important kinases that recognize key cellular substrates that enable GFAP to form a dynamic continuum with microfilaments, integrin receptors, and the extracellular matrix.
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Chung, Chia-Li, Hung-Pei Tsai, Yu-Hua Huang, Shu-Chuan Wu, Chee-Yin Chai, and Aij-Lie Kwan. "Attenuation in Proinflammatory Factors and Reduction in Neuronal Cell Apoptosis and Cerebral Vasospasm by Minocycline during Early Phase after Subarachnoid Hemorrhage in the Rat." BioMed Research International 2021 (December 6, 2021): 1–9. http://dx.doi.org/10.1155/2021/5545727.
Повний текст джерелаАнотація:
Background. Subarachnoid hemorrhage (SAH) is an important subcategory of stroke due to its high mortality rate as well as severe complications such as neurological deficit. It has been suggested that cerebral inflammation is a major factor in advanced brain injury after SAH. Microglia and astrocytes are known supporting cells in the development and maintenance of inflammation in central nervous system. However, the role of microglia and astrocytes in the development of inflammation and neuronal cell apoptosis during the early phase after SAH has not been thoroughly investigated. Materials and Methods. Sprague-Dawley rats were divided into 4 groups ( n = 6 /group): sham group, animals subjected to SAH without treatment, SAH animals pretreated with the microglia inhibitor minocycline (50 mg/kg, ip), and SAH animals pretreated with the astrocyte inhibitor fluorocitrate (50 mg/kg, ip). SAH was induced by injecting autologous blood (1 ml/kg) into the cistern magna on day 0. Pretreatment with minocycline or fluorocitrate was given three days prior to the induction of SAH. Rats were sacrificed 6 hr after SAH, and their cerebral spinal fluids were used to measure protein levels of neuroinflammatory cytokines IL-1β, IL-6, and TNF-α by ELISA. In addition, the cerebral cortex was utilized to determine the levels of caspase-3 by western blot and to evaluate neuronal cell apoptosis by immunohistochemistry staining and detect microglia and astrocyte by immunofluorescence staining for Iba-1 and GFAP. In this study, all SAH animals were given an injection of autologous blood and SAH rats treated with minocycline or fluorocitrate received ip injections on day 1, 2, and 3 before inducing SAH. Neurological outcome was assessed by ambulation and placing/stepping reflex responses on day 7. Results. Immunofluorescence staining showed that SAH induced proliferation of microglia and astrocyte and minocycline inhibited the proliferation of both microglia and astrocyte. However, fluorocitrate inhibited only the proliferation of astrocyte. ELISA analysis showed that SAH upregulated TNF-α and IL-1β, but not IL-6 at 6 hr after SAH. Minocycline, but not fluorocitrate, attenuated the upregulation of TNF-α and IL-1β. Western blot analysis and immunohistochemistry staining showed that SAH induced neuronal cell apoptosis. Pretreatment with minocycline, but not fluorocitrate, decreased SAH-induced neuronal death and cerebral vasospasm. Furthermore, significant improvements in neurobehavioral outcome were seen in the minocycline treatment group, but not in animals treated with fluorocitrate. Conclusions. Microglia may play an important role to regulate neuronal cell apoptosis and cerebral vasospasm through inhibiting inflammation at an early phase after SAH in the rat.
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Bondan, Eduardo Fernandes, Maria de Fátima Monteiro Martins, and Flávio Cesar Viani. "Decreased astrocytic GFAP expression in streptozotocin-induced diabetes after gliotoxic lesion in the rat brainstem." Arquivos Brasileiros de Endocrinologia & Metabologia 57, no. 6 (August 2013): 431–36. http://dx.doi.org/10.1590/s0004-27302013000600004.
Повний текст джерелаАнотація:
OBJECTIVE: The aim of this study was to evaluate the effect of diabetic hyperglycemia on astrocyte function, estimated by means of glial fibrillary acidic protein - GFAP - immunohistochemical expression. MATERIALS AND METHODS: Adult male rats received a single intravenous injection of streptozotocin (50 mg/kg) and were submitted 10 days later to a single injection of 10 microlitres 0.1% EB solution or 0.9% saline solution into the cisterna pontis. Ten microliters of 0.1% EB or 0.9% saline solution were also injected in non-diabetic rats. Animals were anesthetized and perfused through the heart 15 and 31 days after EB or saline injection, and brainstem sections were collected for ultrastructural analysis and GFAP immunohistochemical staining. RESULTS: The GFAP brown-stained areas were evaluated by colorimetry using a computerized image analysis system and the results have shown that diabetes hindered the increase of GFAP astrocyte expression in the EB-injected group compared to non-diabetic animals. However, diabetes did not affect GFAP response in the saline-injected group or in control animals. CONCLUSION: Streptozotocin-induced diabetic condition reduced astrocytic GFAP expression following gliotoxic injury.
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Salois, Garrick, and Jeffrey S. Smith. "Housing Complexity Alters GFAP-Immunoreactive Astrocyte Morphology in the Rat Dentate Gyrus." Neural Plasticity 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/3928726.
Повний текст джерелаАнотація:
Rats used in research are typically housed singly in cages with limited sensory stimulation. There is substantial evidence that housing rats in these conditions lead to numerous neuroanatomical and behavioral abnormalities. Alternatively, rats can be housed in an enriched environment in which rats are housed in groups and given room for exercise and exploration. Enriched environments result in considerable neuroplasticity in the rodent brain. In the dentate gyrus of the hippocampus, enriched environments evoke especially profound neural changes, including increases in the number of neurons and the number of dendritic spines. However, whether changes in astrocytes, a type of glia increasingly implicated in mediating neuroplasticity, are concurrent with these neural changes remains to be investigated. In order to assess morphological changes among astrocytes of the rat dentate gyrus, piSeeDB was used to optically clear 250 μm sections of tissue labeled using GFAP immunohistochemistry. Confocal imaging and image analysis were then used to measure astrocyte morphology. Astrocytes from animals housed in EE demonstrated a reduced distance between filament branch points. Furthermore, the most complex astrocytes were significantly more complex among animals housed in EE compared to standard environments.
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Miguel-Hidalgo, José Javier, Mohadetheh Moulana, Preston Hardin Deloach, and Grazyna Rajkowska. "Chronic Unpredictable Stress Reduces Immunostaining for Connexins 43 and 30 and Myelin Basic Protein in the Rat Prelimbic and Orbitofrontal Cortices." Chronic Stress 2 (January 2018): 247054701881418. http://dx.doi.org/10.1177/2470547018814186.
Повний текст джерелаАнотація:
Background Astrocytes and oligodendrocytes are pathologically altered in dorsolateral prefrontal and orbitofrontal cortices in major depressive disorder. In rat models of stress (major depressive disorder risk factor) astrocyte gap junction protein connexin 43 (Cx43) is reduced in the prelimbic cortex. Astrocyte connexins are recognized to strongly influence myelin maintenance in the central nervous system. However, it is unknown whether stress-related changes in Cx43 and the other major astrocyte connexin, Cx30, occur in the orbitofrontal cortex, or whether connexin changes are concurrent with disturbances in myelination. Methods Frozen sections containing prelimbic cortex and orbitofrontal cortex of rats subjected to 35 days of chronic unpredictable stress and controls (n = 6/group) were immunolabeled for Cx43, Cx30, and myelin basic protein. Density of Cx43 or Cx30 immunoreactive puncta and area fraction of myelin basic protein immunoreactivity were measured in prelimbic cortex and orbitofrontal cortex and results analyzed with t test or Pearson correlations. Results Density of Cx43- and Cx30-positive puncta in both prelimbic cortex and orbitofrontal cortex was lower in chronic unpredictable stress-treated than in control rats. In both regions, the area fraction of myelin basic protein immunoreactivity was also lower in chronic unpredictable stress animals. Myelin basic protein area fraction was positively correlated with the density of Cx43-positive puncta in orbitofrontal cortex, and with Cx30 puncta in prelimbic cortex. Conclusion Low Cx43 and Cx30 after chronic unpredictable stress in rat prelimbic cortex and orbitofrontal cortex suggests that reduced astrocytic gap junction density may generalize to the entire prefrontal cortex. Concurrent reduction of Cx43-, Cx30-, and myelin basic protein-immunolabeled structures is consistent with a mechanism linking changes in astrocyte gap junction proteins and disturbed myelin morphology in depression.
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Du, Yixing, Baofeng Ma, Conrad M. Kiyoshi, Catherine C. Alford, Wei Wang, and Min Zhou. "Freshly dissociated mature hippocampal astrocytes exhibit passive membrane conductance and low membrane resistance similarly to syncytial coupled astrocytes." Journal of Neurophysiology 113, no. 10 (June 2015): 3744–50. http://dx.doi.org/10.1152/jn.00206.2015.
Повний текст джерелаАнотація:
Mature astrocytes exhibit a linear current-to-voltage K+ membrane conductance (passive conductance) and an extremely low membrane resistance ( Rm) in situ. The combination of these electrophysiological characteristics establishes a highly negative and stable membrane potential that is essential for basic functions, such as K+ spatial buffering and neurotransmitter uptake. However, astrocytes are coupled extensively in situ. It remains to be determined whether the observed passive behavior and low Rm are attributable to the intrinsic properties of membrane ion channels or to gap junction coupling in functionally mature astrocytes. In the present study, freshly dissociated hippocampal tissues were used as a new model to examine this basic question in young adult animals. The morphologically intact single astrocytes could be reliably dissociated from animals postnatal day 21 and older. At this animal age, dissociated single astrocytes exhibit passive conductance and resting membrane potential similar to those exhibited by astrocytes in situ. To precisely measure the Rm from single astrocytes, dual-patch single-astrocyte recording was performed. We show that dissociated single astrocytes exhibit a low Rm similarly to syncytial coupled astrocytes. Functionally, the symmetric expression of high-K+ conductance enabled rapid change in the intracellular K+ concentrations in response to changing K+ drive force. Altogether, we demonstrate that freshly dissociated tissue preparation is a highly useful model for study of the functional expression and regulation of ion channels, receptors, and transporters in astrocytes and that passive behavior and low Rm are the intrinsic properties of mature astrocytes.
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Bajenaru, Michaela Livia, Yuan Zhu, Nicolé M. Hedrick, Jessica Donahoe, Luis F. Parada, and David H. Gutmann. "Astrocyte-Specific Inactivation of the Neurofibromatosis 1 Gene (NF1) Is Insufficient for Astrocytoma Formation." Molecular and Cellular Biology 22, no. 14 (July 15, 2002): 5100–5113. http://dx.doi.org/10.1128/mcb.22.14.5100-5113.2002.
Повний текст джерелаАнотація:
ABSTRACT Individuals with the neurofibromatosis 1 (NF1) inherited tumor syndrome develop low-grade gliomas (astrocytomas) at an increased frequency, suggesting that the NF1 gene is a critical growth regulator for astrocytes. In an effort to determine the contribution of the NF1 gene product, neurofibromin, to astrocyte growth regulation and NF1-associated astrocytoma formation, we generated astrocyte-specific Nf1 conditional knockout mice (Nf1GFAPCKO) by using Cre/LoxP technology. Transgenic mice were developed in which Cre recombinase was specifically expressed in astrocytes by embryonic day 14.5. Successive intercrossing with mice bearing a conditional Nf1 allele (Nf1flox) resulted in GFAP-Cre Nf1flox/flox (Nf1GFAPCKO) animals. No astrocytoma formation or neurological impairment was observed in Nf1GFAPCKO mice after 20 months, but increased numbers of proliferating astrocytes were observed in several brain regions. To determine the consequence of Nf1 inactivation at different developmental times, the growth properties of embryonic day 12.5 and postnatal day 2 Nf1 null astrocytes were analyzed. Nf1 null astrocytes exhibited increased proliferation but lacked tumorigenic properties in vitro and did not form tumors when injected into immunocompromised mouse brains in vivo. Collectively, our results suggest that loss of neurofibromin is not sufficient for astrocytoma formation in mice and that other genetic or environmental factors might influence NF1-associated glioma tumorigenesis.
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Hertz, Leif, Dan Song, Baoman Li, Ting Du, Junnan Xu, Li Gu, Ye Chen, and Liang Peng. "Signal Transduction in Astrocytes during Chronic or Acute Treatment with Drugs (SSRIs, Antibipolar Drugs, GABA-ergic Drugs, and Benzodiazepines) Ameliorating Mood Disorders." Journal of Signal Transduction 2014 (February 24, 2014): 1–21. http://dx.doi.org/10.1155/2014/593934.
Повний текст джерелаАнотація:
Chronic treatment with fluoxetine or other so-called serotonin-specific reuptake inhibitor antidepressants (SSRIs) or with a lithium salt “lithium”, carbamazepine, or valproic acid, the three classical antibipolar drugs, exerts a multitude of effects on astrocytes, which in turn modulate astrocyte-neuronal interactions and brain function. In the case of the SSRIs, they are to a large extent due to 5-HT2B-mediated upregulation and editing of genes. These alterations induce alteration in effects of cPLA2, GluK2, and the 5-HT2B receptor, probably including increases in both glucose metabolism and glycogen turnover, which in combination have therapeutic effect on major depression. The ability of increased levels of extracellular K+ to increase [Ca2+]i is increased as a sign of increased K+-induced excitability in astrocytes. Acute anxiolytic drug treatment with benzodiazepines or GABAA receptor stimulation has similar glycogenolysis-enhancing effects. The antibipolar drugs induce intracellular alkalinization in astrocytes with lithium acting on one acid extruder and carbamazepine and valproic acid on a different acid extruder. They inhibit K+-induced and transmitter-induced increase of astrocytic [Ca2+]i and thereby probably excitability. In several cases, they exert different changes in gene expression than SSRIs, determined both in cultured astrocytes and in freshly isolated astrocytes from drug-treated animals.
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Gorbunova, Anna V., Dmitry B. Avdeev, Sergey S. Stepanov, Victor A. Akulinin, Alexander S. Stepanov, Anastasia Yu Shoronova, and Artem A. Samsonov. "Glial Cell Architecture Dynamics in Dentate Gyrus and CA4 Area of Wistar Rat Hippocampus Following 20-minute Occlusion of Common Carotid Arteries." General Reanimatology 15, no. 6 (December 24, 2019): 26–37. http://dx.doi.org/10.15360/1813-9779-2019-6-26-37.
Повний текст джерелаАнотація:
Aim. To study the distribution and spatial organization of dentate gyrus (DG) astrocytes and CA4 area of hippocampus of Wistar rats following 20-minute occlusion of common carotid arteries (OCCA) compared to sham-operated control animals.Material and methods. Histological (Nissl staining with hematoxylin and eosin), immunohistochemical (GFAP, MAP-2) and morphometric methods were used. Astrocytes and neurons in control (sham-operated animals, n = 5) group, after 6 hours (n=5), 1 days (n=5), 3 days (n=5), 7 days (n=5), 14 days (n=5) and 30 days (n=5) after 20-minute OCCA were studied on thin (4 µm) serial frontal sections of the hippocampus. Fractal analysis (ImageJ 1.52; fraclac 2.5 plugin) was used to obtain additional quantitative information on the spatial organization of astrocyte networks. Statistical hypotheses were tested using nonparametric criteria.Results. 30 days after the 20-minute OCCA, only 5.3% of CA4 neurons were irreversibly destroyed and the total numerical density of DG granular cells remained at the control level. Hypertrophy and increased complexity of the spatial organization of astrocyte processes were observed 6 hours and 1 day after OCCA and persisted for 30 days. Astrogliosis was accompanied by an increased relative area of GFAP-positive material and fractal dimension and reduced lacunarity of the astrocyte network. The latter was especially evident in 1, 14 and 30 days after the OCCA.Conclusion. After the 20-minute OCCA, the density of GFAP-positive material increased, the fibroarchitecture reorganized and gained more complexity due to the branching of astrocyte processes. At the same time, the total numerical density of neurons changed only slightly. All this indicated the probable role of astrocytes in post-ischemic activation of natural neuroprotection mechanisms.
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Peixoto, Paulo V., Krishna D. Oliveira, Ticiana N. França, David Driemeier, Marcos D. Duarte, Pedro S. Bezerra Jr, Valíria D. Cerqueira, and Aníbal G. Armién. "Experimental and iatrogenic poisoning by sodium selenite in pigs." Pesquisa Veterinária Brasileira 37, no. 6 (June 2017): 561–69. http://dx.doi.org/10.1590/s0100-736x2017000600005.
Повний текст джерелаАнотація:
ABSTRACT: Following a case of iatrogenic selenium poisoning in a young pig, an experimental study was carry out. Sodium selenite was orally and parenterally administered to 13 pigs that were subdivided into three groups (G1, G2 and G3). The animals in groups G1 and G3 received sodium selenite intramuscularly (IM), G1 received a comercial formula, and G3 received sodium selenite mixed with distilled water at different dosages, and those in group G2 were fed commercial sodium selenite. Acute and subacute poisoning was observed in both groups, although the onset of clinical signs was slower in group G2. Only one pig (in group G1) that had received the highest dose showed a peracute course. Apathy, anorexia, dyspnea, vomiting, muscular tremors, proprioceptive deficit, ataxia and paresis of the hind limbs progressing to the front limbs evolving to tetraplegia were observed. Postmortem findings differed whether the animals received the injected (G1 and G3) or oral (G2) sodium selenite. The liver was moderately atrophic in some animals of G2. Some of the animals in groups G1 and G3 presented with lung edema. One pig in G3 had yellowish-brown areas in the ventral horns of the cervical intumescences of the spinal cord. The most important histological changes were present in the ventral horns of the cervical and lumbar intumescences of the spinal cord. In one animal, changes were present in the brainstem and mesencephalon. The initial lesion was a perivascular and astrocyte edema that progressing to lysis and death of astrocytes and neurons. In the chronic stage of the lesions, there were extensive areas of liquefaction necrosis with perivascular lymphocytic and histiocytic infiltration and occasional eosinophils. It seems that disruption of the blood-brain barrier due to astrocyte edema is the most likely mechanism of CNS lesion.
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Thalman, Carine, Guilherme Horta, Lianyong Qiao, Heiko Endle, Irmgard Tegeder, Hong Cheng, Gregor Laube, et al. "Synaptic phospholipids as a new target for cortical hyperexcitability and E/I balance in psychiatric disorders." Molecular Psychiatry 23, no. 8 (May 9, 2018): 1699–710. http://dx.doi.org/10.1038/s41380-018-0053-1.
Повний текст джерелаАнотація:
Summary Lysophosphatidic acid (LPA) is a synaptic phospholipid, which regulates cortical excitation/inhibition (E/I) balance and controls sensory information processing in mice and man. Altered synaptic LPA signaling was shown to be associated with psychiatric disorders. Here, we show that the LPA-synthesizing enzyme autotaxin (ATX) is expressed in the astrocytic compartment of excitatory synapses and modulates glutamatergic transmission. In astrocytes, ATX is sorted toward fine astrocytic processes and transported to excitatory but not inhibitory synapses. This ATX sorting, as well as the enzymatic activity of astrocyte-derived ATX are dynamically regulated by neuronal activity via astrocytic glutamate receptors. Pharmacological and genetic ATX inhibition both rescued schizophrenia-related hyperexcitability syndromes caused by altered bioactive lipid signaling in two genetic mouse models for psychiatric disorders. Interestingly, ATX inhibition did not affect naive animals. However, as our data suggested that pharmacological ATX inhibition is a general method to reverse cortical excitability, we applied ATX inhibition in a ketamine model of schizophrenia and rescued thereby the electrophysiological and behavioral schizophrenia-like phenotype. Our data show that astrocytic ATX is a novel modulator of glutamatergic transmission and that targeting ATX might be a versatile strategy for a novel drug therapy to treat cortical hyperexcitability in psychiatric disorders.
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Gerhold, Lynnette M., and Phyllis M. Wise. "Vasoactive Intestinal Polypeptide Regulates Dynamic Changes in Astrocyte Morphometry: Impact on Gonadotropin-Releasing Hormone Neurons." Endocrinology 147, no. 5 (May 1, 2006): 2197–202. http://dx.doi.org/10.1210/en.2005-1262.
Повний текст джерелаАнотація:
Recent studies suggest that astrocytes modulate the GnRH-induced LH surge. In particular, we have shown that the surface area of astrocytes that ensheath GnRH neurons exhibits diurnal rhythms. Vasoactive intestinal polypeptide (VIP) influences numerous aspects of astrocyte function in multiple brain regions and is a neurotransmitter in the suprachiasmatic nucleus (SCN) that affects GnRH neurons. The goals of this study were to: 1) assess whether astrocytes that surround GnRH neurons express VIP receptors, 2) determine the effects VIP suppression in the SCN on the morphometry of astrocytes surrounding GnRH neurons, and 3) assess whether this effect mimics aging-like changes in surface area of astrocytes. Young rats were ovariectomized (d 0), implanted with cannulae into the SCN (d 5), injected with VIP antisense (antioligo) or random sequence oligonucleotides, implanted with capsules containing 17β-estradiol dissolved in oil (d 7), and perfused at 0300, 1400, and 1800 h (d 9). Brains were processed for immunocytochemistry. Our results demonstrate that astrocytes in close apposition to GnRH neurons express VIP receptors. Antioligo treatment blocked diurnal rhythms in surface area of astrocytes ensheathing GnRH neurons. The absence of diurnal rhythms resembles observations in middle-aged rats. Together these findings suggest that the ability of the VIP-containing neurons in the SCN to relay diurnal information to GnRH neurons may be by influencing dynamic changes in the morphometry of astrocytes that surround GnRH neurons. Furthermore, the absence of a VIP rhythm in aging animals may lead to altered GnRH activity via astrocyte-dependent mechanisms.
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Hammond, Sean L., Collin M. Bantle, Katriana A. Popichak, Katie A. Wright, Delaney Thompson, Catalina Forero, Kelly S. Kirkley, Pranav U. Damale, Edwin K. P. Chong та Ronald B. Tjalkens. "NF-κB Signaling in Astrocytes Modulates Brain Inflammation and Neuronal Injury Following Sequential Exposure to Manganese and MPTP During Development and Aging". Toxicological Sciences 177, № 2 (21 липня 2020): 506–20. http://dx.doi.org/10.1093/toxsci/kfaa115.
Повний текст джерелаАнотація:
Abstract Chronic exposure to manganese (Mn) is associated with neuroinflammation and extrapyramidal motor deficits resembling features of Parkinson’s disease. Activation of astrocytes and microglia is implicated in neuronal injury from Mn but it is not known whether early life exposure to Mn may predispose glia to more severe inflammatory responses during aging. We therefore examined astrocyte nuclear factor kappa B (NF-κB) signaling in mediating innate immune inflammatory responses during multiple neurotoxic exposures spanning juvenile development into adulthood. MnCl2 was given in drinking water for 30-day postweaning to both wildtype mice and astrocyte-specific knockout (KO) mice lacking I kappa B kinase 2, the central upstream activator of NF-κB. Following juvenile exposure to Mn, mice were subsequently administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at 4 months of age. Animals were evaluated for behavioral alterations and brain tissue was analyzed for catecholamine neurotransmitters. Stereological analysis of neuronal and glial cell counts from multiple brain regions indicated that juvenile exposure to Mn amplified glial activation and neuronal loss from MPTP exposure in the caudate-putamen and globus pallidus, as well as increased the severity of neurobehavioral deficits in open field activity assays. These alterations were prevented in astrocyte-specific I kappa B kinase 2 KO mice. Juvenile exposure to Mn increased the number of neurotoxic A1 astrocytes expressing C3 as well as the number of activated microglia in adult mice following MPTP challenge, both of which were inhibited in KO mice. These results demonstrate that exposure to Mn during juvenile development heightens the innate immune inflammatory response in glia during a subsequent neurotoxic challenge through NF-κB signaling in astrocytes.
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Lechuga-Sancho, Alfonso M., Ana I. Arroba, Laura M. Frago, Cristina García-Cáceres, Arancha Delgado-Rubín de Célix, Jesús Argente, and Julie A. Chowen. "Reduction in the Number of Astrocytes and Their Projections Is Associated with Increased Synaptic Protein Density in the Hypothalamus of Poorly Controlled Diabetic Rats." Endocrinology 147, no. 11 (November 1, 2006): 5314–24. http://dx.doi.org/10.1210/en.2006-0766.
Повний текст джерелаАнотація:
Processes under hypothalamic control, such as thermogenesis, feeding behavior, and pituitary hormone secretion, are disrupted in poorly controlled diabetes, but the underlying mechanisms are poorly understood. Because glial cells regulate neurosecretory neurons through modulation of synaptic inputs and function, we investigated the changes in hypothalamic glia in rats with streptozotocin-induced diabetes mellitus. Hypothalamic glial fibrillary acidic protein (GFAP) levels decreased significantly 6 wk after diabetes onset. This was coincident with decreased GFAP immunoreactive surface area, astrocyte number, and the extension of GFAP immunoreactive processes/astrocyte in the arcuate nucleus. Cell death, analyzed by terminal deoxyuridine 5-triphosphate nick-end labeling and ELISA, increased significantly at 4 wk of diabetes. Proliferation, measured by Western blot for proliferating cell nuclear antigen and immunostaining for phosphorylated histone H-3, decreased in the hypothalamus of diabetic rats throughout the study, becoming significantly reduced by 8 wk. Both proliferation and death affected astroctyes because both phosphorylated histone H-3- and terminal deoxyuridine 5-triphosphate nick-end labeling-labeled cells were GFAP positive. Western blot analysis revealed that postsynaptic density protein 95 and the presynaptic proteins synapsin I and synaptotagmin increased significantly at 8 wk of diabetes, suggesting increased hypothalamic synaptic density. Thus, in poorly controlled diabetic rats, there is a decrease in the number of hypothalamic astrocytes that is correlated with modifications in synaptic proteins and possibly synaptic inputs. These morphological changes in the arcuate nucleus could be involved in neurosecretory and metabolic changes seen in diabetic animals.
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Ghaemi, Amir, Leila Alizadeh, Shahnaz Babaei, Maryam Jafarian, Maryam Khaleghi Ghadiri, Sven G. Meuth, Stjepana Kovac, and Ali Gorji. "Astrocyte-mediated inflammation in cortical spreading depression." Cephalalgia 38, no. 4 (April 3, 2017): 626–38. http://dx.doi.org/10.1177/0333102417702132.
Повний текст джерелаАнотація:
Background Cortical spreading depression (CSD) related diseases such as migraine, cerebrovascular diseases, and epilepsy have been associated with reactive astrocytosis, yet the mechanisms of these tissue changes remain unclear. CSD-induced inflammatory response has been proposed to play a role in some neurological disorders and thus may also contribute to reactive astrocytosis. Methods Using ex vivo brain slices and in vitro astrocytic cultures, we aimed to characterize CSD related changes in astrocytes and markers of inflammation by immunocyto- and immunohistochemistry. CSD was induced by application of KCl (3 mol/l) on neocortical tissues. The application of KCl was repeated weekly over the course of four weeks. Results CSD induced an increase in the mean number and volume of astrocytes in rat brain tissue when compared to controls, whereas no changes in neuronal numbers and volumes were seen. These cell-type specific changes, suggestive of reactive astrocytosis, were paralleled by an increased expression of protein markers indicative of astrocytes and neuroinflammation in ex vivo brain slices of animals undergoing CSD when compared to sham-treated controls. Cultured astrocytes showed an increased expression of the immune modulatory enzyme indoleamine 2,3-dioxygenase and an elevated expression of the pro-inflammatory markers, IL-6, IL-1β, and TNFα in addition to increased levels of toll like receptors (TLR3 and TLR4) and astrocytic markers after induction of CSD. Conclusion These findings indicate that CSD related reactive astrocytosis is linked to an upregulation of inflammatory markers. Targeting inflammation with already approved and available immunomodulatory treatments may thus represent a strategy to combat or ameliorate CSD-related disease.
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Bondan, Eduardo Fernandes, Carolina Vieira Cardoso, Maria de Fátima Monteiro Martins, and Rosemari Otton. "Memory impairments and increased GFAP expression in hippocampal astrocytes following hypercaloric diet in rats." Arquivos de Neuro-Psiquiatria 77, no. 9 (September 2019): 601–8. http://dx.doi.org/10.1590/0004-282x20190091.
Повний текст джерелаАнотація:
ABSTRACT Objective: Hypothalamic inflammation and glial fibrillary acidic protein (GFAP) overexpression in astrocytes are well described in obese animals, as are some cognitive and memory deficits. As the hippocampus plays important roles in the consolidation of information, this investigation aimed to observe the memory function and the astrocyte expression of GFAP in the hippocampus of rats that received either a hypercaloric or a normocaloric diet. Methods: Adult male Wistar rats received a high-fat (cafeteria) or a standard diet for 60 days. On the 61st day, the rats were submitted to the novel object recognition (NOR) test at three and 24 hours after the first contact with objects, to assess short-term and long-term memory, respectively. Thereafter, the rats were euthanized and their brains were collected for GFAP immunohistochemical investigation in the hippocampus (CA1, CA2, CA3 areas) and hypothalamus (periventricular and arcuate nuclei). Astrocytic reactivity was assessed by morphometry. Different white adipose tissue depots and brown adipose tissue were weighed to calculate the adiposity index. Results: The hypercaloric diet increased body weight gain, adiposity index, white adipose tissue weight (epididymal, subcutaneous and retroperitoneal) and brown adipose tissue weight. Rats fed with the hypercaloric diet showed short-term and long-term memory impairments in the NOR test, as well as increased GFAP expression in astrocytes from all analyzed hypothalamic and hippocampal areas. Conclusion: This astrogliosis suggests that the neuroinflammatory response also occurs in the hippocampus and may be involved in the memory losses observed in obese/overweight animals.
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Fæste, Christiane Kruse, Anita Solhaug, Marion Gaborit, Florian Pierre, and Dominique Massotte. "Neurotoxic Potential of Deoxynivalenol in Murine Brain Cell Lines and Primary Hippocampal Cultures." Toxins 14, no. 1 (January 10, 2022): 48. http://dx.doi.org/10.3390/toxins14010048.
Повний текст джерелаАнотація:
Chronic exposure to the mycotoxin deoxynivalenol (DON) from grain-based food and feed affects human and animal health. Known consequences include entereopathogenic and immunotoxic defects; however, the neurotoxic potential of DON has only come into focus more recently due to the observation of behavioural disorders in exposed farm animals. DON can cross the blood-brain barrier and interfere with the homeostasis/functioning of the nervous system, but the underlying mechanisms of action remain elusive. Here, we have investigated the impact of DON on mouse astrocyte and microglia cell lines, as well as on primary hippocampal cultures by analysing different toxicological endpoints. We found that DON has an impact on the viability of both glial cell types, as shown by a significant decrease of metabolic activity, and a notable cytotoxic effect, which was stronger in the microglia. In astrocytes, DON caused a G1 phase arrest in the cell cycle and a decrease of cyclic-adenosine monophosphate (cAMP) levels. The pro-inflammatory cytokine tumour necrosis factor (TNF)-α was secreted in the microglia in response to DON exposure. Furthermore, the intermediate filaments of the astrocytic cytoskeleton were disturbed in primary hippocampal cultures, and the dendrite lengths of neurons were shortened. The combined results indicated DON’s considerable potential to interfere with the brain cell physiology, which helps explain the observed in vivo neurotoxicological effects.
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Ranjbar Taklimie, Fatemeh, Natalie Gasterich, Miriam Scheld, Ralf Weiskirchen, Cordian Beyer, Tim Clarner, and Adib Zendedel. "Hypoxia Induces Astrocyte-Derived Lipocalin-2 in Ischemic Stroke." International Journal of Molecular Sciences 20, no. 6 (March 13, 2019): 1271. http://dx.doi.org/10.3390/ijms20061271.
Повний текст джерелаАнотація:
Ischemic stroke causes rapid hypoxic damage to the core neural tissue which is followed by graded chronological tissue degeneration in the peri-infarct zone. The latter process is mainly triggered by neuroinflammation, activation of inflammasomes, proinflammatory cytokines, and pyroptosis. Besides microglia, astrocytes play an important role in the fine-tuning of the inflammatory network in the brain. Lipocalin-2 (LCN2) is involved in the control of innate immune responses, regulation of excess iron, and reactive oxygen production. In this study, we analyzed LCN2 expression in hypoxic rat brain tissue after ischemic stroke and in astrocyte cell cultures receiving standardized hypoxic treatment. Whereas no LCN2-positive cells were seen in sham animals, the number of LCN2-positive cells (mainly astrocytes) was significantly increased after stroke. In vitro studies with hypoxic cultured astroglia revealed that LCN2 expression is significantly increased after only 2 h, then further increased, followed by a stepwise decline. The expression pattern of several proinflammatory cytokines mainly followed that profile in wild type (WT) but not in cultured LCN2-deficient astrocytes. Our data revealed that astrocytes are an important source of LCN2 in the peri-infarct region under hypoxic conditions. However, we must also stress that brain-intrinsic LCN2 after the initial hypoxia period might come from other sources such as invaded immune cells and peripheral organs via blood circulation. In any case, secreted LCN2 might have an influence on peripheral organ functions and the innate immune system during brain hypoxia.
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Wang, Xiaodan, Ying Hu, Wenxin Liu, Yuanyuan Ma, Xi Chen, Ting Xue, and Donghong Cui. "Molecular Basis of GABA Hypofunction in Adolescent Schizophrenia-Like Animals." Neural Plasticity 2021 (April 15, 2021): 1–15. http://dx.doi.org/10.1155/2021/9983438.
Повний текст джерелаАнотація:
Schizophrenia is a neurodevelopmental disorder that NMDA receptor (NMDAR) hypofunction appears centrally involved. Schizophrenia typically emerges in adolescence or early adulthood. Electrophysiological and several neurochemical changes have linked the GABA deficits to abnormal behaviors induced by NMDAR hypofunction. However, few studies have systematically investigated the molecular basis of GABA deficits, especially during adolescence. To address this issue, we transiently administrated MK-801 to mice on PND 10, which exhibited schizophrenia-relevant deficits in adolescence. Slice recording showed reduced GABA transmission and PVI+ hypofunction, indicating GABAergic hypofunction. Cortical proteomic evaluation combined with analysis of single cell data from the Allen Brain showed that various metabolic processes were enriched in top ranks and differentially altered in excitatory neurons, GABAergic interneurons, and glial cells. Notably, the GABA-related amino acid metabolic process was disturbed in both astrocytes and interneurons, in which we found a downregulated set of GABA-related proteins (GAD65, SYNPR, DBI, GAT3, SN1, and CPT1A). They synergistically regulate GABA synthesis, release, reuptake, and replenishment. Their downregulation indicates impaired GABA cycle and homeostasis regulated by interneuron-astrocyte communication in adolescence. Our findings on molecular basis of GABA deficits could provide potential drug targets of GABAergic rescue for early prevention and intervention.
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Deng, You-liang, Yu-long Ma, Zeng-li Zhang, Li-xia Zhang, Hang Guo, Pei Qin, Yu-shu Hou, Zi-jun Gao та Wu-gang Hou. "Astrocytic N-Myc Downstream-regulated Gene–2 Is Involved in Nuclear Transcription Factor κB–mediated Inflammation Induced by Global Cerebral Ischemia". Anesthesiology 128, № 3 (1 березня 2018): 574–86. http://dx.doi.org/10.1097/aln.0000000000002044.
Повний текст джерелаАнотація:
Abstract Background Inflammation is a key element in the pathophysiology of cerebral ischemia. This study investigated the role of N-Myc downstream-regulated gene–2 in nuclear transcription factor κB–mediated inflammation in ischemia models. Methods Mice (n = 6 to 12) with or without nuclear transcription factor κB inhibitor pyrrolidinedithiocarbamate pretreatment were subjected to global cerebral ischemia for 20 min. Pure astrocyte cultures or astrocyte-neuron cocultures (n = 6) with or without pyrrolidinedithiocarbamate pretreatment were exposed to oxygen-glucose deprivation for 4 h or 2 h. Astrocytic nuclear transcription factor κB and N-Myc downstream-regulated gene–2 expression, proinflammatory cytokine secretion, neuronal apoptosis and survival, and memory function were analyzed at different time points after reperfusion or reoxygenation. Proinflammatory cytokine secretion was also studied in lentivirus-transfected astrocyte lines after reoxygenation. Results Astrocytic nuclear transcription factor κB and N-Myc downstream-regulated gene–2 expression and proinflammatory cytokine secretion increased after reperfusion or reoxygenation. Pyrrolidinedithiocarbamate pretreatment significantly reduced N-Myc downstream-regulated gene–2 expression and proinflammatory cytokine secretion in vivo and in vitro, reduced neuronal apoptosis induced by global cerebral ischemia/reperfusion (from 65 ± 4% to 47 ± 4%, P = 0.0375) and oxygen-glucose deprivation/reoxygenation (from 45.6 ± 0.2% to 22.0 ± 4.0%, P < 0.001), and improved memory function in comparison to vehicle-treated control animals subjected to global cerebral ischemia/reperfusion. N-Myc downstream-regulated gene–2 lentiviral knockdown reduced the oxygen-glucose deprivation-induced secretion of proinflammatory cytokines. Conclusions Astrocytic N-Myc downstream-regulated gene–2 is up-regulated after cerebral ischemia and is involved in nuclear transcription factor κB–mediated inflammation. Pyrrolidinedithiocarbamate alleviates ischemia-induced neuronal injury and hippocampal-dependent cognitive impairment by inhibiting increases in N-Myc downstream-regulated gene–2 expression and N-Myc downstream-regulated gene–2—mediated inflammation.
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Bento-Torres, J., L. L. Sobral, R. R. Reis, R. B. de Oliveira, D. C. Anthony, P. F. C. Vasconcelos, and Cristovam Wanderley Picanço Diniz. "Age and Environment Influences on Mouse Prion Disease Progression: Behavioral Changes and Morphometry and Stereology of Hippocampal Astrocytes." Oxidative Medicine and Cellular Longevity 2017 (2017): 1–18. http://dx.doi.org/10.1155/2017/4504925.
Повний текст джерелаАнотація:
Because enriched environment (EE) and exercise increase and aging decreases immune response, we hypothesized that environmental enrichment and aging will, respectively, delay and increase prion disease progression. Mice dorsal striatum received bilateral stereotaxic intracerebral injections of normal or ME7 prion infected mouse brain homogenates. After behavior analysis, animals were euthanized and their brains processed for astrocyte GFAP immunolabeling. Our analysis related to the environmental influence are limited to young adult mice, whereas age influence refers to aged mice raised on standard cages. Burrowing activity began to reduce in ME7-SE two weeks before ME7-EE, while no changes were apparent in ME7 aged mice (ME7-A). Object placement recognition was impaired in ME7-SE, NBH-A, and ME7-A but normal in all other groups. Object identity recognition was impaired in ME7-A. Cluster analysis revealed two morphological families of astrocytes in NBH-SE animals, three in NBH-A and ME7-A, and four in NBH-EE, ME7-SE, and ME7-EE. As compared with control groups, astrocytes from DG and CA3 prion-diseased animals show significant numerical and morphological differences and environmental enrichment did not reverse these changes but induced different morphological changes in GFAP+ hippocampal astroglia. We suggest that environmental enrichment and aging delayed hippocampal-dependent behavioral and neuropathological signs of disease progression.
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Jovanović, Violeta, Jelica Despotović, Mario Balo, Ivan Zaletel, Sanja Despotović, and Nela Puškaš. "Increased astrocyte representation in the hippocampus of 5xFAD mice." Medicinski podmladak 72, no. 2 (2021): 5–10. http://dx.doi.org/10.5937/mp72-32451.
Повний текст джерелаАнотація:
Introduction: Alzheimer's disease is the most common neurodegenerative disorder, characterized by the formation of amyloid plaques and the neurofibrillary tangles in the brain of an ill person, leading to neuronal damage and loss. Activation of astrocytes and astrogliosis occurs along with this process. Due to ethical limitations in working with human tissue, numerous transgenic animal models have been developed to study the pathogenesis of these processes. Early Ab deposition is observed in the cortex and the hippocampus. Aim: This study aimed to determine the difference in the presence of GFAP positive cells in the hippocampus between transgenic 5xFAD mice aged 36 weeks and their corresponding controls. Material and Methods: The 5xFAD mice model of Alzheimer's disease was used, characterized by early formation of amyloid plaques but without the presence of neurofibrillar tangles. Transgenic and control animals were sacrificed at 36 weeks of age. The visualization of GFAP-positive cells in the hippocampus of their brains was done by using immunohistochemistry and antibody for glial fibrillary acidic protein - GFAP, the major marker of astrocytes. Quantification of immuno-reactivity was done by using the Icy software system. Results: There was a statistically significant difference in the expression of GFAP in the dentate gyrus and the granular zone of the hippocampus between the transgenic and control group at 36 weeks of age, while the significant change in the CA1-3 regions was not observed between investigated groups. Conclusion: Obtained results confirm the involvement of astrogliosis in the pathophysiology of Alzheimer's disease and indicate an earlier occurrence of astrogliosis in the dentate gyrus and granular zone, in relation to other regions of the hippocampus, in the 36-week-old 5xFAD mice.
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Garg, Saurabh K., Daniel T. Lioy, Sharon J. Knopp, and John M. Bissonnette. "Conditional depletion of methyl-CpG-binding protein 2 in astrocytes depresses the hypercapnic ventilatory response in mice." Journal of Applied Physiology 119, no. 6 (September 15, 2015): 670–76. http://dx.doi.org/10.1152/japplphysiol.00411.2015.
Повний текст джерелаАнотація:
Mice that are deficient in the transcription factor methyl-CpG-binding protein 2 (MeCP2) have a depressed hypercapnic ventilatory response (HCVR). The expression of MeCP2 can be selectively removed from astrocytes or neurons, thus offering a tool to dissect the role of this transcription factor in astrocytes from that in neurons. Studies were carried out in the progeny of mice that were a cross between those harboring a tamoxifen (TAM)-inducible Cre recombinase transgene driven by the human astrocytic glial fibrillary acidic protein (hGFAP) promoter, or Cre recombinase under control of the synapsin promoter, with mice containing a Cre-excisable exon III in the Mecp2 gene. The TAM-conditional excision of the Mecp2 exon allowed the respiratory CO2 response to be studied in the same animals before and after selective depletion of MeCP2 in astrocytes. Immunohistochemistry showed that following TAM treatment only ∼20% of GFAP-labeled cells in the retrotrapazoid nucleus and in the raphé magnus were positive for MeCP2. The slope of the relative increase in minute ventilation as a function of 1, 3, and 5% inspired CO2 was depressed in mice with depleted astrocyte MeCP2 compared with wild-type littermates. In contrast, selective depletion of MeCP2 in neurons did not significantly affect slope. While neurons which constitute the respiratory network ultimately determine the ventilatory response to CO2, this study demonstrates that loss of MeCP2 in astrocytes alone is sufficient to result in a dramatic attenuation of the HCVR. We propose that the glial contribution to HCVR is under the control of the MeCP2 gene.
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Tahir, Waqas, Basant Abdulrahman, Dalia H. Abdelaziz, Simrika Thapa, Rupali Walia, and Hermann M. Schätzl. "An astrocyte cell line that differentially propagates murine prions." Journal of Biological Chemistry 295, no. 33 (June 19, 2020): 11572–83. http://dx.doi.org/10.1074/jbc.ra120.012596.
Повний текст джерелаАнотація:
Prion diseases are fatal infectious neurodegenerative disorders in human and animals caused by misfolding of the cellular prion protein (PrPC) into the pathological isoform PrPSc. Elucidating the molecular and cellular mechanisms underlying prion propagation may help to develop disease interventions. Cell culture systems for prion propagation have greatly advanced molecular insights into prion biology, but translation of in vitro to in vivo findings is often disappointing. A wider range of cell culture systems might help overcome these shortcomings. Here, we describe an immortalized mouse neuronal astrocyte cell line (C8D1A) that can be infected with murine prions. Both PrPC protein and mRNA levels in astrocytes were comparable with those in neuronal and non-neuronal cell lines permitting persistent prion infection. We challenged astrocytes with three mouse-adapted prion strains (22L, RML, and ME7) and cultured them for six passages. Immunoblotting results revealed that the astrocytes propagated 22L prions well over all six passages, whereas ME7 prions did not replicate, and RML prions replicated only very weakly after five passages. Immunofluorescence analysis indicated similar results for PrPSc. Interestingly, when we used prion conversion activity as a readout in real-time quaking-induced conversion assays with RML-infected cell lysates, we observed a strong signal over all six passages, comparable with that for 22L-infected cells. These data indicate that the C8D1A cell line is permissive to prion infection. Moreover, the propagated prions differed in conversion and proteinase K–resistance levels in these astrocytes. We propose that the C8D1A cell line could be used to decipher prion strain biology.
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Komitova, Mila, Ekaterina Perfilieva, Bengt Mattsson, Peter S. Eriksson, and Barbro B. Johansson. "Effects of Cortical Ischemia and Postischemic Environmental Enrichment on Hippocampal Cell Genesis and Differentiation in the Adult Rat." Journal of Cerebral Blood Flow & Metabolism 22, no. 7 (July 2002): 852–60. http://dx.doi.org/10.1097/00004647-200207000-00010.
Повний текст джерелаАнотація:
The study aimed to elucidate the effects of cortical ischemia and postischemic environmental enrichment on hippocampal cell genesis. A cortical infarct was induced by a permanent ligation of the middle cerebral artery distal to the striatal branches in 6-month-old spontaneously hypertensive rats. Bromodeoxyuridine (BrdU) was administered as 7 consecutive daily injections starting 24 hours after surgery and animals were housed in standard or enriched environment. Four weeks after completed BrdU administration, BrdU incorporation and its co-localization with the neuronal markers NeuN and calbindin D28k, and the astrocytic marker glial fibrillary acidic protein in the granular cell layer and subgranular zone of the hippocampal dentate gyrus were determined with immunohistochemistry and were quantified stereologically. Compared with sham-operated rats, rats with cortical infarcts had a five-to sixfold ipsilateral increase in BrdU-labeled cells. About 80% of the new cells were neurons. Differential postischemic housing did not influence significantly the total number of surviving BrdU-labeled cells or newborn neurons. However, postischemic environmental enrichment increased the ipsilateral generation of astrocytes normalizing the astrocyte-to-neuron ratio, which was significantly reduced in rats housed in standard environment postischemically.
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Louw, Deon F., Tetsuy Masada, and Garnette R. Sutherland. "Ischemic Neuronal Injury is Ameliorated by Astrocyte Activation." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 25, no. 2 (May 1998): 102–7. http://dx.doi.org/10.1017/s0317167100033692.
Повний текст джерелаАнотація:
ABSTRACT:Background:The motivation of this study was to more precisely define the in vivo role of astrocytes in forebrain ischemia. Controversy exists in the literature as to whether they protect or injure neurons in this setting.Methods:Astrocytes in the rat hippocampus were disabled with stereotactic administration of a gliotoxin, ethidium bromide, 3 days prior to induction of forebrain ischemia. The extent of neuronal injury in this group was compared to a control category receiving intrahippocampal saline only.Results:Saline-injected animals demonstrated decreased hippocampal CA1 sector injury, and increased gliosis on the side of the injection compared to the contralateral side (P < 0.01) or ethidium bromide-treated animals (P < 0.05).Conclusion:The results suggest that activated astrocytes are protective to neurons subjected to an ischemic insult. This may result from their ability to elaborate neurotrophic factors, buffer potassium and metabolize a variety of neurotransmitters.
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Pla, Laura, Miriam Illa, Carla Loreiro, Mari Carmen Lopez, Paula Vázquez-Aristizabal, Britta Anna Kühne, Marta Barenys, Elisenda Eixarch, and Eduard Gratacós. "Structural Brain Changes during the Neonatal Period in a Rabbit Model of Intrauterine Growth Restriction." Developmental Neuroscience 42, no. 5-6 (2020): 217–29. http://dx.doi.org/10.1159/000512948.
Повний текст джерелаАнотація:
Background: Intrauterine growth restriction (IUGR) is associated with abnormal neurodevelopment, but the associated structural brain changes are poorly documented. The aim of this study was to describe in an animal model the brain changes at the cellular level in the gray and white matter induced by IUGR during the neonatal period. Methods: The IUGR model was surgically induced in pregnant rabbits by ligating 40–50% of the uteroplacental vessels in 1 horn, whereas the uteroplacental vessels of the contralateral horn were not ligated. After 5 days, IUGR animals from the ligated horn and controls from the nonligated were delivered. On the day of delivery, perinatal data and placentas were collected. On postnatal day 1, functional changes were first evaluated, and thereafter, neuronal arborization in the frontal cortex and density of pre-oligodendrocytes, astrocytes, and microglia in the corpus callosum were evaluated. Results: Higher stillbirth in IUGR fetuses together with a reduced birth weight as compared to controls was evidenced. IUGR animals showed poorer functional results, an altered neuronal arborization pattern, and a decrease in the pre-oligodendrocytes, with no differences in microglia and astrocyte densities. Conclusions: Overall, in the rabbit model used, IUGR is related to functional and brain changes evidenced already at birth, including changes in the neuronal arborization and abnormal oligodendrocyte maturation.
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van Marle, Guido, Joseph Antony, Heather Ostermann, Christopher Dunham, Tracey Hunt, William Halliday, Ferdinand Maingat, et al. "West Nile Virus-Induced Neuroinflammation: Glial Infection and Capsid Protein-Mediated Neurovirulence." Journal of Virology 81, no. 20 (August 1, 2007): 10933–49. http://dx.doi.org/10.1128/jvi.02422-06.
Повний текст джерелаАнотація:
ABSTRACT West Nile virus (WNV) infection causes neurological disease at all levels of the neural axis, accompanied by neuroinflammation and neuronal loss, although the underlying mechanisms remain uncertain. Given the substantial activation of neuroinflammatory pathways observed in WNV infection, we hypothesized that WNV-mediated neuroinflammation and cell death occurred through WNV infection of both glia and neurons, which was driven in part by WNV capsid protein expression. Analysis of autopsied neural tissues from humans with WNV encephalomyelitis (WNVE) revealed WNV infection of both neurons and glia. Upregulation of proinflammatory genes, CXCL10, interleukin-1β, and indolamine-2′,3′-deoxygenase with concurrent suppression of the protective astrocyte-specific endoplasmic reticulum stress sensor gene, OASIS (for old astrocyte specifically induced substance), was evident in WNVE patients compared to non-WNVE controls. These findings were supported by increased ex vivo expression of these proinflammatory genes in glia infected by WNV-NY99. WNV infection caused endoplasmic reticulum stress gene induction and apoptosis in neurons but did not affect glial viability. WNV-infected astrocytic cells secreted cytotoxic factors, which caused neuronal apoptosis. The expression of the WNV-NY99 capsid protein in neurons and glia by a Sindbis virus-derived vector (SINrep5-WNVc) caused neuronal death and the release of neurotoxic factors by infected astrocytes, coupled with proinflammatory gene induction and suppression of OASIS. Striatal implantation of SINrep5-WNVC induced neuroinflammation in rats, together with the induction of CXCL10 and diminished OASIS expression, compared to controls. Moreover, magnetic resonance neuroimaging showed edema and tissue injury in the vicinity of the SINrep5-WNVc implantation site compared to controls, which was complemented by neurobehavioral abnormalities in the SINrep5-WNVc-implanted animals. These studies underscore the important interactions between the WNV capsid protein and neuroinflammation in the pathogenesis of WNV-induced neurological disorders.
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Vignal, Nicolas, Anne-Cécile Boulay, Carine San, Martine Cohen-Salmon, Nathalie Rizzo-Padoin, Laure Sarda-Mantel, Xavier Declèves, Salvatore Cisternino, and Benoît Hosten. "Astroglial Connexin 43 Deficiency Protects against LPS-Induced Neuroinflammation: A TSPO Brain µPET Study with [18F]FEPPA." Cells 9, no. 2 (February 7, 2020): 389. http://dx.doi.org/10.3390/cells9020389.
Повний текст джерелаАнотація:
Astroglial connexin 43 (Cx43) has been recognized as a crucial immunoregulating factor in the brain. Its inactivation leads to a continuous immune recruitment, cytokine expression modification and a specific humoral autoimmune response against the astrocytic extracellular matrix but without brain lesions or cell lysis. To assess the impact of Cx43 deletion on the brain’s inflammatory response, TSPO expression was studied by positron emission tomography (PET) imaging with a specific radioligand, [18F]FEPPA, in basal conditions or upon Lipopolysaccharides (LPS)-induced inflammatory challenge. Astroglial Cx43-deleted mice underwent [18F]FEPPA PET/CT dynamic imaging with or without LPS injection (5 mg/kg) 24 h before imaging. Quantification and pharmacokinetic data modelling with a 2TCM-1K compartment model were performed. After collecting the mice brains, TSPO expression was quantified and localized by Western blot and FISH analysis. We found that astroglial Cx43 deficiency does not significantly alter TSPO expression in the basal state as observed with [18F]FEPPA PET imaging, FISH and Western blot analysis. However, deletion of astrocyte Cx43 abolishes the LPS-induced TSPO increase. Autoimmune encephalopathy observed in astroglial Cx43-deleted mice does not involve TSPO overexpression. Consistent with previous studies showing a unique inflammatory status in the absence of astrocyte Cx43, we show that a deficient expression of astrocytic Cx43 protects the animals from LPS-induced neuroinflammation as addressed by TSPO expression.
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Tran, Cam Ha T., and Grant R. Gordon. "Astrocyte and Microvascular Imaging in Awake Animals Using Two-Photon Microscopy." Microcirculation 22, no. 3 (April 2015): 219–27. http://dx.doi.org/10.1111/micc.12188.
Повний текст джерела
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Koyama, Yutaka. "Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders." International Journal of Molecular Sciences 22, no. 9 (April 21, 2021): 4333. http://dx.doi.org/10.3390/ijms22094333.
Повний текст джерелаАнотація:
In brain disorders, reactive astrocytes, which are characterized by hypertrophy of the cell body and proliferative properties, are commonly observed. As reactive astrocytes are involved in the pathogenesis of several brain disorders, the control of astrocytic function has been proposed as a therapeutic strategy, and target molecules to effectively control astrocytic functions have been investigated. The production of brain endothelin-1 (ET-1), which increases in brain disorders, is involved in the pathophysiological response of the nervous system. Endothelin B (ETB) receptors are highly expressed in reactive astrocytes and are upregulated by brain injury. Activation of astrocyte ETB receptors promotes the induction of reactive astrocytes. In addition, the production of various astrocyte-derived factors, including neurotrophic factors and vascular permeability regulators, is regulated by ETB receptors. In animal models of Alzheimer’s disease, brain ischemia, neuropathic pain, and traumatic brain injury, ETB-receptor-mediated regulation of astrocytic activation has been reported to improve brain disorders. Therefore, the astrocytic ETB receptor is expected to be a promising drug target to improve several brain disorders. This article reviews the roles of ETB receptors in astrocytic activation and discusses its possible applications in the treatment of brain disorders.
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Martins, Emerson Fachin, and Gerson Chadi. "Glial reaction in the hippocampus after global cardiogenic ischemia." Acta Cirurgica Brasileira 16, no. 1 (March 2001): 05–14. http://dx.doi.org/10.1590/s0102-86502001000100003.
Повний текст джерелаАнотація:
Many experimental surgerical procedures have been perfomed in the analyse of the phenomenon of brain trophism and plasticity, however undesirable intercorrence can occour leading to specific changes in the results that should be taken into attention. To study this issue we have promoted a transient cardiogenic interruption of the blood flow together with a transient occlusion of the bilateral common carotid arteries (2VO) in rats and analysed the state of activation of astrocyte and microglia by means of the glial fibrillary acidic protein (GFAP) and OX42 immunohistochemistry, respectively. Rats were submitted to incomplete global cerebral ischemia (IGCI) by occlusion of the bilateral carotid arteries for 30 minutes. During the IGCI surgical, some rats received a higher dose of the chloral hydrate anaesthesia which promoted a cardiogenic interruption of the blood flow (CIBF) for a period of 10 minutes followed by and prompt reperfusion. During that period, animals were submited to a cardiac massage and ventilated. Sham operation were made in control animals. Rats were killed and their brains processed 14 days after the surgery. The animals that have received a IGCI showed a slight astroglial and microglial reaction in all subfields of the hippocampal formation, however the animal submitted to CIBF showed a massive infiltration of the reactive astrocyte and microglia in CA1 subfield. This results demonstrated that a transient occlusion of the bilateral common carotid arteries leads to activation of glial cells in the hippocampus, however this response can be remarkable changed in animal developing a transient systemic hypoperfusion during surgery. Thus, an accurated monitoration of the hemodinamic condition of the animal has to be done in experimental models of brain ischemia and the results have to be analysed in view of this aspect.
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Shayea, Abdulaziz M. F., Alyaa M. A. Mousa, Waleed M. Renno, Mohammed Shaban Nadar, Bedoor Qabazard, and Mariam H. M. Yousif. "Chronic Treatment With Hydrogen Sulfide Donor GYY4137 Mitigates Microglial and Astrocyte Activation in the Spinal Cord of Streptozotocin-Induced Diabetic Rats." Journal of Neuropathology & Experimental Neurology 79, no. 12 (November 26, 2020): 1320–43. http://dx.doi.org/10.1093/jnen/nlaa127.
Повний текст джерелаАнотація:
Abstract Long-term diabetic patients suffer immensely from diabetic neuropathy. This study was designed to investigate the effects of hydrogen sulfide (H2S) on peripheral neuropathy, activation of microglia, astrocytes, and the cascade secretion of proinflammatory cytokines in the streptozotocin (STZ)-induced peripheral diabetic neuropathy rat model. STZ-induced diabetic rats were treated with the water-soluble, slow-releasing H2S donor GYY4137 (50 mg/kg; i.p.) daily for 4 weeks. Antiallodynic/antihyperalgesic activities were evaluated using different tests and histopathological changes and the expression of proinflammatory cytokines in the spinal cord were examined. GYY4137 treatment produced neuroprotective effects in the spinal cord of diabetic animals and modulated their sensory deficits. The treatment decreased allodynia (p < 0.05) and mechanical hyperalgesia (p < 0.01) and restored thermal hyperalgesia (p < 0.001) compared with diabetic rats. The treatment decreased the microglial response and increased astrocyte counts in spinal cord gray and white matter compared with untreated diabetic rats. Proinflammatory cytokines were reduced in the treated group compared with diabetic rats. These results suggest that H2S has a potentially ameliorative effect on the neuropathic pain through the control of astrocyte activation and microglia-mediated inflammation, which may be considered as a possible treatment of peripheral nerve hypersensitivity in diabetic patients.
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Bondan, Eduardo Fernandes, and Maria de Fátima Monteiro Martins. "Blood-brain barrier breakdown and repair following gliotoxic drug injection in the brainstem of streptozotocin-diabetic rats." Arquivos de Neuro-Psiquiatria 70, no. 3 (March 2012): 221–25. http://dx.doi.org/10.1590/s0004-282x2012000300013.
Повний текст джерелаАнотація:
Ethidium bromide (EB) causes local astrocytic disappearance, with glia limitans disruption and blood-brain barrier (BBB) breakdown. The aim of this study was to evaluate the BBB integrity after the injection of 0.1% EB or 0.9% saline solution into the cisterna pontis of Wistar rats submitted or not to the streptozotocin diabetogenic model. Brainstem sections were collected from 24 hours to 31 days post-injection for ultrastructural analysis and glial fibrillary acidic protein immunohistochemical staining. Some animals received colloidal carbon ink by intravenous route at the same periods. In rats injected with EB, results revealed astrocyte disappearance and leakage of carbon particles beginning at 48 hours and persisting for 7 days in non-diabetic rats and for 15 days in the diabetic ones, although, in both groups, several areas remained devoid of astrocytic processes up to 31 days. In rats injected with saline, there was no sign of astrocytic loss or carbon particles leakage.
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De Simone, Uliana, Francesca Caloni, Laura Gribaldo, and Teresa Coccini. "Human Co-culture Model of Neurons and Astrocytes to Test Acute Cytotoxicity of Neurotoxic Compounds." International Journal of Toxicology 36, no. 6 (November 2017): 463–77. http://dx.doi.org/10.1177/1091581817739428.
Повний текст джерелаАнотація:
Alternative methods and their use in planning and conducting toxicology experiments have become essential for modern toxicologists, thus reducing or replacing living animals. Although in vitro human co-culture models allow the establishment of biologically relevant cell–cell interactions that recapitulate the tissue microenvironment and better mimic its physiology, the number of publications is limited specifically addressing this scientific area and utilizing this test method which could provide an additional valuable model in toxicological studies. In the present study, an in vitro model based on central nervous system (CNS) cell co-cultures was implemented using a transwell system combining human neuronal cells (SH-SY5Y cell line) and glial cells, namely astrocytes (D384 cell line), to investigate neuroprotection of D384 on SH-SY5Y and vice versa. The model was applied to test acute (24-48 hours) cytotoxicity of 3 different neurotoxicants: (1) methyl mercury (1-2.5 μM), (2) Fe3O4 nanoparticles (1-100 μg/mL), and (3) methylglyoxal (0.5-1 mM). Data were compared to mono-cultures evaluating the mitochondrial function and cell morphology. The results clearly showed that all compounds tested affected the mitochondrial activity and cell morphology in both mono-culture and co-culture conditions. However, astrocytes, when cultured together with neurons, diminish the neurotoxicant-induced cytotoxic effects that occurred in neurons cultured alone, and astrocytes become more resistant in the presence of neurons. This human CNS co-culture system seems a suitable cell model to feed high-throughput acute screening platforms and to evaluate both human neuronal and astrocytic toxicity and neuroprotective effects of new and emerging materials (eg, nanomaterials) and new products with improved sensitivity due to the functional neuron–astrocyte metabolic interactions.
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Freitas-Andrade, Moises, Nan Wang, John F. Bechberger, Marijke De Bock, Paul D. Lampe, Luc Leybaert, and Christian C. Naus. "Targeting MAPK phosphorylation of Connexin43 provides neuroprotection in stroke." Journal of Experimental Medicine 216, no. 4 (March 14, 2019): 916–35. http://dx.doi.org/10.1084/jem.20171452.
Повний текст джерелаАнотація:
Connexin43 (Cx43) function is influenced by kinases that phosphorylate specific serine sites located near its C-terminus. Stroke is a powerful inducer of kinase activity, but its effect on Cx43 is unknown. We investigated the impact of wild-type (WT) and knock-in Cx43 with serine to alanine mutations at the protein kinase C (PKC) site Cx43S368A, the casein kinase 1 (CK1) sites Cx43S325A/328Y/330A, and the mitogen-activated protein kinase (MAPK) sites Cx43S255/262/279/282A (MK4) on a permanent middle cerebral artery occlusion (pMCAO) stroke model. We demonstrate that MK4 transgenic animals exhibit a significant decrease in infarct volume that was associated with improvement in behavioral performance. An increase in astrocyte reactivity with a concomitant decrease in microglial reactivity was observed in MK4 mice. In contrast to WT, MK4 astrocytes displayed reduced Cx43 hemichannel activity. Pharmacological blockade of Cx43 hemichannels with TAT-Gap19 also significantly decreased infarct volume in WT animals. This study provides novel molecular insights and charts new avenues for therapeutic intervention associated with Cx43 function.
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Desky, Fitria, Hermanto Tri Joewono, and Widjiati Widjiati. "FR 50% in pregnancy results in different neuron and glial cell count (astrocytes, olygodendrocytes, and microglia) in the cerebrum and cerebellum of newborn Rattus norvegicus." Majalah Obstetri & Ginekologi 27, no. 2 (September 19, 2019): 56. http://dx.doi.org/10.20473/mog.v27i22019.56-65.
Повний текст джерелаАнотація:
Objectives: To analyze the difference neuronal and glial (astrocytes, oligodendrocyte, microglia) cell count in cerebrum and cerebellum of Rattus norvegicus newborns with 50% food restriction and control group.Materials and Methods: This was an analytical experimental study with single blind randomized post test only control group design using animals subjects Rattus norvegicus. This study was conducted at Animal laboratory, Veterinary Faculty, Universitas Airlangga. Animal subjects were divided into FR50% group and control. Neuron and glial (astrocytes, oligodendrocytes, microglia) counts were analyzed using comparison test, with CI 95%.Results: There was a significant difference in cerebrum and cerebellum neuron cell count between intervention and control group (9.88+3.59 vs 16.88+2.553; p=0.000 and 7.5+1.789 vs 11.44+4.56; p=0.02). There was no difference in cerebrum and cerebellum glial cell count. There was a significant difference in cerebellum astrocyte between intervention and control group (80.94+24.255 vs 59.69+18.77; p=0.02) but no difference in cerebrum. There was a significant difference in cerebrum and cerebellum oligodendrocyte between intervention and control group (14.06+12.195 vs 25.13+8.609; p<0.000 and 13.63+6.712 vs 24.00+8.862; p=0.001), and there were significant difference in cerebrum and cerebellum microglia cell between intervention and control group (5.25+3.435 vs 4.94+3.838; p=0.620 and 8.81+4.119 vs 5.25+1.483; p=0.004).Conclusion: Food Restriction 50% (FR50%) in Rattus norvegicus decreased cerebrum and cerebellum neuron cell and oligodendrocyte count and increased cerebrum and cerebellum microglial count.
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Michinaga, Shotaro, and Yutaka Koyama. "Pathophysiological Responses and Roles of Astrocytes in Traumatic Brain Injury." International Journal of Molecular Sciences 22, no. 12 (June 15, 2021): 6418. http://dx.doi.org/10.3390/ijms22126418.
Повний текст джерелаАнотація:
Traumatic brain injury (TBI) is immediate damage caused by a blow to the head resulting from traffic accidents, falls, and sporting activity, which causes death or serious disabilities in survivors. TBI induces multiple secondary injuries, including neuroinflammation, disruption of the blood–brain barrier (BBB), and brain edema. Despite these emergent conditions, current therapies for TBI are limited or insufficient in some cases. Although several candidate drugs exerted beneficial effects in TBI animal models, most of them failed to show significant effects in clinical trials. Multiple studies have suggested that astrocytes play a key role in the pathogenesis of TBI. Increased reactive astrocytes and astrocyte-derived factors are commonly observed in both TBI patients and experimental animal models. Astrocytes have beneficial and detrimental effects on TBI, including promotion and restriction of neurogenesis and synaptogenesis, acceleration and suppression of neuroinflammation, and disruption and repair of the BBB via multiple bioactive factors. Additionally, astrocytic aquaporin-4 is involved in the formation of cytotoxic edema. Thus, astrocytes are attractive targets for novel therapeutic drugs for TBI, although astrocyte-targeting drugs have not yet been developed. This article reviews recent observations of the roles of astrocytes and expected astrocyte-targeting drugs in TBI.
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Zhou, Zhiwen, Kazuki Okamoto, Junya Onodera, Toshimitsu Hiragi, Megumi Andoh, Masahito Ikawa, Kenji F. Tanaka, Yuji Ikegaya, and Ryuta Koyama. "Astrocytic cAMP modulates memory via synaptic plasticity." Proceedings of the National Academy of Sciences 118, no. 3 (January 15, 2021): e2016584118. http://dx.doi.org/10.1073/pnas.2016584118.
Повний текст джерелаАнотація:
Astrocytes play a key role in brain homeostasis and functions such as memory. Specifically, astrocytes express multiple receptors that transduce signals via the second messenger cAMP. However, the involvement of astrocytic cAMP in animal behavior and the underlying glial–neuronal interactions remains largely unknown. Here, we show that an increase in astrocytic cAMP is sufficient to induce synaptic plasticity and modulate memory. We developed a method to increase astrocytic cAMP levels in vivo using photoactivated adenylyl cyclase and found that increased cAMP in hippocampal astrocytes at different time points facilitated memory formation but interrupted memory retention via NMDA receptor–dependent plasticity. Furthermore, we found that the cAMP-induced modulation of memory was mediated by the astrocyte–neuron lactate shuttle. Thus, our study unveils a role of astrocytic cAMP in brain function by providing a tool to modulate astrocytic cAMP in vivo.
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Gould, Timothy, Lixin Chen, Zsuzsa Emri, Tiina Pirttimaki, Adam C. Errington, Vincenzo Crunelli, and H. Rheinallt Parri. "GABA B receptor-mediated activation of astrocytes by gamma-hydroxybutyric acid." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1654 (October 19, 2014): 20130607. http://dx.doi.org/10.1098/rstb.2013.0607.
Повний текст джерелаАнотація:
The gamma-aminobutyric acid (GABA) metabolite gamma-hydroxybutyric acid (GHB) shows a variety of behavioural effects when administered to animals and humans, including reward/addiction properties and absence seizures. At the cellular level, these actions of GHB are mediated by activation of neuronal GABA B receptors (GABA B Rs) where it acts as a weak agonist. Because astrocytes respond to endogenous and exogenously applied GABA by activation of both GABA A and GABA B Rs, here we investigated the action of GHB on astrocytes on the ventral tegmental area (VTA) and the ventrobasal (VB) thalamic nucleus, two brain areas involved in the reward and proepileptic action of GHB, respectively, and compared it with that of the potent GABA B R agonist baclofen. We found that GHB and baclofen elicited dose-dependent (ED 50 : 1.6 mM and 1.3 µM, respectively) transient increases in intracellular Ca 2+ in VTA and VB astrocytes of young mice and rats, which were accounted for by activation of their GABA B Rs and mediated by Ca 2+ release from intracellular store release. In contrast, prolonged GHB and baclofen exposure caused a reduction in spontaneous astrocyte activity and glutamate release from VTA astrocytes. These findings have key (patho)physiological implications for our understanding of the addictive and proepileptic actions of GHB.
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Jin, Myungwon, Jong-Heon Kim, Eunha Jang, Young Mi Lee, Hyung Soo Han, Dong Kyun Woo, Dong Ho Park, Hyun Kook, and Kyoungho Suk. "Lipocalin-2 Deficiency Attenuates Neuroinflammation and Brain Injury after Transient Middle Cerebral Artery Occlusion in Mice." Journal of Cerebral Blood Flow & Metabolism 34, no. 8 (April 30, 2014): 1306–14. http://dx.doi.org/10.1038/jcbfm.2014.83.
Повний текст джерелаАнотація:
Lipocalin-2 (LCN2) is a secreted protein of the lipocalin family, but little is known about the expression or the role of LCN2 in the central nervous system. Here, we investigated the role of LCN2 in ischemic stroke using a rodent model of transient cerebral ischemia. Lipocalin-2 expression was highly induced in the ischemic brain and peaked at 24 hours after reperfusion. After transient middle cerebral artery occlusion, LCN2 was predominantly expressed in astrocytes and endothelial cells, whereas its receptor (24p3R) was mainly detected in neurons, astrocytes, and endothelial cells. Brain infarct volumes, neurologic scores, blood–brain barrier (BBB) permeabilities, glial activation, and inflammatory mediator expression were significantly lower in LCN2-defkient mice than in wild-type animals. Lipocalin-2 deficiency also attenuated glial neurotoxicity in astrocyte/neuron cocultures after oxygen-glucose deprivation. Our results indicate LCN2 has a critical role in brain injury after ischemia/reperfusion, and that LCN2 may contribute to neuronal cell death in the ischemic brain by promoting neurotoxic glial activation, neuroinflammation, and BBB disruption.