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1
Jollet, Maxence, Kevin Nay, Angèle Chopard, Marie-Pierre Bareille, Arnaud Beck, Vincent Ollendorff, Barbara Vernus et al. "Does Physical Inactivity Induce Significant Changes in Human Gut Microbiota? New Answers Using the Dry Immersion Hypoactivity Model". Nutrients 13, n. 11 (29 ottobre 2021): 3865. http://dx.doi.org/10.3390/nu13113865.
Testo completoAbstract (sommario):
Gut microbiota, a major contributor to human health, is influenced by physical activity and diet, and displays a functional cross-talk with skeletal muscle. Conversely, few data are available on the impact of hypoactivity, although sedentary lifestyles are widespread and associated with negative health and socio-economic impacts. The study aim was to determine the effect of Dry Immersion (DI), a severe hypoactivity model, on the human gut microbiota composition. Stool samples were collected from 14 healthy men before and after 5 days of DI to determine the gut microbiota taxonomic profiles by 16S metagenomic sequencing in strictly controlled dietary conditions. The α and β diversities indices were unchanged. However, the operational taxonomic units associated with the Clostridiales order and the Lachnospiraceae family, belonging to the Firmicutes phylum, were significantly increased after DI. Propionate, a short-chain fatty acid metabolized by skeletal muscle, was significantly reduced in post-DI stool samples. The finding that intestine bacteria are sensitive to hypoactivity raises questions about their impact and role in chronic sedentary lifestyles.
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Park, Il Ho, Jae-Jin Kim, Jiwon Chun, Young Chul Jung, Jeong Ho Seok, Hae-Jeong Park e Jong Doo Lee. "Medial prefrontal default-mode hypoactivity affecting trait physical anhedonia in schizophrenia". Psychiatry Research: Neuroimaging 171, n. 3 (marzo 2009): 155–65. http://dx.doi.org/10.1016/j.pscychresns.2008.03.010.
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Guo, Yixin, Yiti Fu e Wenjun Sun. "50 Hz Magnetic Field Exposure Inhibited Spontaneous Movement of Zebrafish Larvae through ROS-Mediated syn2a Expression". International Journal of Molecular Sciences 24, n. 8 (20 aprile 2023): 7576. http://dx.doi.org/10.3390/ijms24087576.
Testo completoAbstract (sommario):
Extremely low frequency electromagnetic field (ELF-EMF) exists widely in public and occupational environments. However, its potential adverse effects and the underlying mechanism on nervous system, especially behavior are still poorly understood. In this study, zebrafish embryos (including a transfected synapsin IIa (syn2a) overexpression plasmid) at 3 h post-fertilization (hpf) were exposed to a 50-Hz magnetic field (MF) with a series of intensities (100, 200, 400 and 800 μT, respectively) for 1 h or 24 h every day for 5 days. Results showed that, although MF exposure did not affect the basic development parameters including hatching rate, mortality and malformation rate, yet MF at 200 μT could significantly induce spontaneous movement (SM) hypoactivity in zebrafish larvae. Histological examination presented morphological abnormalities of the brain such as condensed cell nucleus and cytoplasm, increased intercellular space. Moreover, exposure to MF at 200 μT inhibited syn2a transcription and expression, and increased reactive oxygen species (ROS) level as well. Overexpression of syn2a could effectively rescue MF-induced SM hypoactivity in zebrafish. Pretreatment with N-acetyl-L-cysteine (NAC) could not only recover syn2a protein expression which was weakened by MF exposure, but also abolish MF-induced SM hypoactivity. However, syn2a overexpression did not affect MF-increased ROS. Taken together, the findings suggested that exposure to a 50-Hz MF inhibited spontaneous movement of zebrafish larvae via ROS-mediated syn2a expression in a nonlinear manner.
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Tou, Janet C. L., e Charles E. Wade. "Determinants Affecting Physical Activity Levels In Animal Models1". Experimental Biology and Medicine 227, n. 8 (settembre 2002): 587–600. http://dx.doi.org/10.1177/153537020222700806.
Testo completoAbstract (sommario):
Weight control is dependent on energy balance. Reduced energy expenditure (EE) associated with decreased physical activity is suggested to be a major underlying cause in the increasing prevalence of weight gain and obesity. Therefore, a better understanding of the biological determinants involved in the regulation of physical activity is essential. To facilitate interpretation in humans, it is helpful to consider the evidence from animal studies. This review focuses on animal studies examining the biological determinants influencing activity and potential implications to human. It appears that physical activity is influenced by a number of parameters. However, regardless of the parameter involved, body weight appears to play an underlying role in the regulation of activity. Furthermore, the regulation of activity associated with body weight appears to occur only after the animal achieves a critical weight. This suggests that activity levels are a consequence rather than a contributor to weight control. However, the existence of an inverse weight-activity relationship remains inconclusive. Confounding the results are the multifactorial nature of physical activity and the lack of appropriate measuring devices. Furthermore, many determinants of body weight are closely interlocked, making it difficult to determine whether a single, combination, or interaction of factors is important for the regulation of activity. For example, diet-induced obesity, aging, lesions to the ventral medial hypothalamus, and genetics all produce hypoactivity. Providing a better understanding of the biological determinants involved in the regulation of activity has important implications for the development of strategies for the prevention of weight gain leading to obesity and subsequent morbidity and mortality in the human population.
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Boisseau, Nathalie, Nicolas Barnich e Christelle Koechlin-Ramonatxo. "The Nutrition-Microbiota-Physical Activity Triad: An Inspiring New Concept for Health and Sports Performance". Nutrients 14, n. 5 (22 febbraio 2022): 924. http://dx.doi.org/10.3390/nu14050924.
Testo completoAbstract (sommario):
The human gut microbiota is currently the focus of converging interest in many diseases and sports performance. This review presents gut microbiota as a real “orchestra conductor” in the host’s physio(patho)logy due to its implications in many aspects of health and disease. Reciprocally, gut microbiota composition and activity are influenced by many different factors, such as diet and physical activity. Literature data have shown that macro- and micro-nutrients influence gut microbiota composition. Cumulative data indicate that gut bacteria are sensitive to modulation by physical activity, as shown by studies using training and hypoactivity models. Sports performance studies have also presented interesting and promising results. Therefore, gut microbiota could be considered a “pivotal” organ for health and sports performance, leading to a new concept: the nutrition-microbiota-physical activity triad. The next challenge for the scientific and medical communities is to test this concept in clinical studies. The long-term aim is to find the best combination of the three elements of this triad to optimize treatments, delay disease onset, or enhance sports performance. The many possibilities offered by biotic supplementation and training modalities open different avenues for future research.
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SOTHMANN, MARK, e G. K. KASTELLO. "Simulated weightlessness to induce chronic hypoactivity of brain norepinephrine for exercise and stress studies". Medicine & Science in Sports & Exercise 29, n. 1 (gennaio 1997): 39–44. http://dx.doi.org/10.1097/00005768-199701000-00007.
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Moreno Ávila, Claudia Leticia, Jorge H. Limón-Pacheco, Magda Giordano e Verónica M. Rodríguez. "Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice". Journal of Toxicology 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/4763434.
Testo completoAbstract (sommario):
Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced hypoactivity at six months and other behaviors such as rearing and on-wall rearing and barbering showed both increases and decreases. No alterations on aggressive behavior or monoamines levels in striatum or frontal cortex were observed. A significant decrease in the expression of mRNA for D2 receptors was found in striatum of mice exposed to 5.0 mg As/L. This study provides evidence for the use of dopamine receptor D2 as potential target of arsenic toxicity in the dopaminergic system.
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Lim, Charmaine J. M., Jack Bray, Sanna K. Janhunen, Bettina Platt e Gernot Riedel. "Mouse Exploratory Behaviour in the Open Field with and without NAT-1 EEG Device: Effects of MK801 and Scopolamine". Biomolecules 14, n. 8 (15 agosto 2024): 1008. http://dx.doi.org/10.3390/biom14081008.
Testo completoAbstract (sommario):
One aspect of reproducibility in preclinical research that is frequently overlooked is the physical condition in which physiological, pharmacological, or behavioural recordings are conducted. In this study, the physical conditions of mice were altered through the attachments of wireless electrophysiological recording devices (Neural Activity Tracker-1, NAT-1). NAT-1 devices are miniaturised multichannel devices with onboard memory for direct high-resolution recording of brain activity for >48 h. Such devices may limit the mobility of animals and affect their behavioural performance due to the added weight (total weight of approximately 3.4 g). The mice were additionally treated with saline (control), N-methyl-D-aspartate (NMDA) receptor antagonist MK801 (0.85 mg/kg), or the muscarinic acetylcholine receptor blocker scopolamine (0.65 mg/kg) to allow exploration of the effect of NAT-1 attachments in pharmacologically treated mice. We found only minimal differences in behavioural outcomes with NAT-1 attachments in standard parameters of locomotor activity widely reported for the open field test between the drug treatments. Hypoactivity was globally observed as a consistent outcome in the MK801-treated mice and hyperactivity in scopolamine groups regardless of NAT-1 attachments. These data collectively confirm the reproducibility for combined behavioural, pharmacological, and physiological endpoints even in the presence of lightweight wireless data loggers. The NAT-1 therefore constitutes a pertinent tool for investigating brain activity in, e.g., drug discovery and models of neuropsychiatric and/or neurodegenerative diseases with minimal effects on pharmacological and behavioural outcomes.
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FitzGerald, Leah. "Blunted Affect is Associated With Hypothalamic—Pituitary—Adrenal Axis (HPA) Hypoactivity and Elevated CSF-Interleukin-1 Beta (IL-1β) in Response to Lumbar Puncture". Biological Research For Nursing 13, n. 2 (1 novembre 2010): 164–74. http://dx.doi.org/10.1177/1099800410383558.
Testo completoAbstract (sommario):
Objective. Proinflammatory activity has been suggested as one of the psychophysiological mechanisms responsible for the health risks associated with stress and mood disorders. There have been limited studies evaluating central immune and hypothalamic— pituitary—adrenal (HPA) axis responses to experimental stress in healthy women. The current study compared, under a controlled condition, the baseline measures and biological and psychological responses to a physical stressor (lumbar puncture [LP]) of healthy women who exhibited an abnormal serum cortisol response (nonresponders [NRs]) to the LP to those of normal controls (responders [Rs]), allowing assessment of stress responsivity and the functional integrity of the feedback system of the HPA axis, sympathetic nervous system (SNS), and neuroimmune axis. Method. Serum adrenocorticotropic hormone (ACTH), cortisol, interleukin (IL)-6, IL-1sR, and central IL-1β, IL-6, norepineprhine (NE), corticotropin-releasing factor (CRF), and affective states (using the Stress Symptom Rating Questionnaire) were measured in five NRs and seven Rs. Results. Compared with NR subjects, Rs had significantly higher levels of ACTH and central IL-1β, higher ratings of attention, and lower perceived stress and anxiety. There were no differences between the groups in serum cortisol, IL-6, or IL-1sR or in central IL-6, NE, and CRF. Conclusions. Women with significantly elevated IL-1β (NRs) responded to an extreme physical stressor with an attenuated HPA system and abnormal subjective ratings compared to healthy women with lower values of central IL-1β. These findings support the suppression of the effects of HPA-axis cortisol on proinflammatory cytokine production. It is possible that these differences in the psychoneuroimmunological profiles of NRs will lead to increased psychobiological vulnerability and predict future health risk.
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Pereira-Nunes, Joana, Ana Vilan, Ana Grangeia e Renata d’Oliveira. "Novel Arthrogryposis Multiplex Congenita Presentation in a Newborn With Pierpont Syndrome". Journal of Investigative Medicine High Impact Case Reports 11 (gennaio 2023): 232470962211506. http://dx.doi.org/10.1177/23247096221150637.
Testo completoAbstract (sommario):
Pierpont syndrome is a rare and recently described multiple congenital anomaly syndrome, classically characterized by global developmental delay, distinctive facial dysmorphic features, and abnormal fat distribution in distal limbs. Only few cases were previously documented. We report a case of a term male neonate admitted to the neonatal intensive care unit because of feeding difficulties. Intrauterine growth restriction, microcephaly, and bilateral equinovarus foot were diagnosed in the second trimester, and prenatal array comparative genomic hybridization showed no abnormality. Physical examination revealed bilateral flexion deformities of wrists, elbows, knees and clubfoot, large hands and feet, deep palmar and plantar grooves, and calcaneo-plantar fat pads. Craniofacial dysmorphism, axial hypotonia, and hypoactivity were also observed. Due to the presence of congenital and non-progressive joint contractures, arthrogryposis multiplex congenita (AMC) was considered. A comprehensive diagnostic workup, including a Next Generation Sequencing target panel, was performed but did not establish a diagnosis. The clinical exome identified an heterozygous pathogenic variant in the TBL1XR1 gene (NM_001321194.1: c.1337A>G, p.[Tyr446Cys]), allowing Pierpont syndrome diagnosis. Our case stands out for reporting the novel AMC presentation in a Pierpont syndrome newborn. The broader and precocious genetic testing proved to be an essential clarifying diagnostic tool. Our patient supports the relation between the p.Tyr446Cys sequence variant in TBL1XR1 gene with this rare syndrome, reinforcing its association with a distinctive and recognizable phenotype, as well as expanding its clinical features to include AMC.
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Ofori, Edward, Madeline Hooten, Marcus Ortega, Jordan Barajas e Dara James. "IDENTIFYING MARKERS OF NEURODEGENERATION FOR MOTORIC COGNITIVE RISK SYNDROME". Innovation in Aging 7, Supplement_1 (1 dicembre 2023): 688. http://dx.doi.org/10.1093/geroni/igad104.2235.
Testo completoAbstract (sommario):
Abstract Cognitive disorders, particularly dementia, are a major cause of disability in the elderly population. Gait disturbances, decreased grip strength and memory complaints are early signs of dementia that can occur well before the disease manifests. To better understand the close interactions between the physical and cognitive domains, the concept of Motoric Cognitive Risk Syndrome (MCRS) has been proposed. We had 25 older adults (10 cognitively unimpaired and 15 with MCRS) generate multiple force pulses at 15% of their maximum voluntary contraction with a fixed duration of 2 seconds for each pulse in which participants must rely on visual spatial abilities to gauge the amount force required in real-time to reach the criterion target. We also assessed neurofilament light chain levels also a blood-based marker of neuronal loss. Our results indicate the MCRS group demonstrated blood oxygenation level dependent (BOLD) hyperactivity in visual cortical/hippocampal regions, parahippocampal regions, and dorsolateral prefrontal cortex. The MCRS group also demonstrated BOLD hypoactivity in primarily involved with movement, such as cerebellar lobules, supplementary motor areas, middle frontal gyrus, and prefrontal cortex areas.be useful in tracking disease progression. We also found a significant strong positive correlation (0.83) between serum NFL levels and Right BOLD coefficients only for the CI group. This finding suggests that these motor task fMRI measures may be specific in tracking neurodegeneration in MCRS group. Overall, the current preliminary findings provide novel insights into the neurobiological mechanisms underlying early changes in Alzheimer’s disease and related dementias.
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Morash, Michael G., Kelly H. Soanes, John C. Achenbach e Lee D. Ellis. "Assessing the Morphological and Behavioral Toxicity of Catechol Using Larval Zebrafish". International Journal of Molecular Sciences 23, n. 14 (20 luglio 2022): 7985. http://dx.doi.org/10.3390/ijms23147985.
Testo completoAbstract (sommario):
Catechol is a ubiquitous chemical used in the manufacturing of fragrances, pharmaceuticals and flavorants. Environmental exposure occurs in a variety of ways through industrial processes, during pyrolysis and in effluent, yet despite its prevalence, there is limited information regarding its toxicity. While the genotoxicity and gastric carcinogenicity of catechol have been described in depth, toxicological studies have potentially overlooked a number of other effects relevant to humans. Here, we have made use of a general and behavioral larval zebrafish toxicity assay to describe previously unknown catechol-based toxicological phenomena. Behavioral testing revealed catechol-induced hypoactivity at concentrations an order of magnitude lower than observable endpoints. Catechol exposure also resulted in punctate melanocytes with concomitant decreases in the expression of pigment production and regulation markers mitfa, mc1r and tyr. Because catechol is converted into a number of toxic metabolites by tyrosinase, an enzyme found almost exclusively in melanocytes, an evaluation of the effects of catechol on these cells is critical to evaluating the safety of this chemical. This work provides insights into the toxic nature of catechol and highlights the benefits of the zebrafish larval testing platform in being able to dissect multiple aspects of toxicity with one model.
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imeno Ruiz, Sara J., María Benedit Gómez, Paula Touza Pol, Amaia García Arratibel e Alejandro López Escobar. "A Case of Infant Botulism Treated with Human-Derived Antitoxin". SVOA Paediatrics 3, n. 2 (24 aprile 2024): 30–37. http://dx.doi.org/10.58624/svoapd.2024.03.061.
Testo completoAbstract (sommario):
Background: Infant botulism is a severe and rare illness due to the ingestion of the neurotoxin secreted by Clostridium botulinum and is a neuroparalytic descendant acute disease which is reversible, treatable and preventable. Symptoms vary from mild hypotonia to respiratory failure and sudden death. Clinical Observation: A four-months-old female baby taken to the Emergency Room because of hypoactivity and failure to eat. Parents reported constipation for the last 5 days. The physical examination showed a hypoactive baby with sleep tendency and mild axial hypotonia. During the next 48 hours there is a progressive worsening of the clinical condition with severe axial hypotonia, generalized weakness, weak cry, increasing difficulty in sucking and swallowing and increase of respiratory secretions together with weak cough reflex. An electromyogram was performed with normal results. Parents denied giving the baby honey, infusions or any other food other than milk or cereals. Although there was no clear epidemiological history, infant botulism was suspected, and contact was made with the local Health Department and a direct toxin analysis was requested from blood and fecal samples. She received treatment with human derived botulism antitoxin (BabyBIG®) with a favorable outcome. The diagnosis was confirmed by the detection of the botulism toxin B in the patient's stools. Comments: Infant botulism, although it is a rare disease in our environment, requires a high level of suspicion to make an early diagnosis and initiate a timely and specific treatment and thus reduce complications and the course of the disease.
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Di Bisceglie Caballero, Sonia, Aurelia Ces, Martine Liberge, Frederic Ambroggi, Marianne Amalric e Abdel-Mouttalib Ouagazzal. "Optogenetic Globus Pallidus Stimulation Improves Motor Deficits in 6-Hydroxydopamine-Lesioned Mouse Model of Parkinson’s Disease". International Journal of Molecular Sciences 24, n. 9 (27 aprile 2023): 7935. http://dx.doi.org/10.3390/ijms24097935.
Testo completoAbstract (sommario):
Excessive inhibition of the external globus pallidus (GPe) by striatal GABAergic neurons is considered a central mechanism contributing to motor symptoms of Parkinson’s disease (PD). While electrophysiological findings support this view, behavioral studies assessing the beneficial effects of global GPe activations are scarce and the reported results are controversial. We used an optogenetic approach and the standard unilateral 6-hydroxydopamine nigrostriatal dopamine (DA) lesion model of PD to explore the effects of GPe photostimulation on motor deficits in mice. Global optogenetic GPe inhibition was used in normal mice to verify whether it reproduced the typical motor impairment induced by DA lesions. GPe activation improved ipsilateral circling, contralateral forelimb akinesia, locomotor hypoactivity, and bradykinesia in 6-OHDA-lesioned mice at ineffective photostimulation parameters (532 nm, 5 Hz, 3 mW) in normal mice. GPe photoinhibition (450 nm, 12 mW) had no effect on locomotor activity and forelimb use in normal mice. Bilateral photoinhibition (450 nm, 6 mW/side) reduced directed exploration and improved working memory performances indicating that recruitment of GPe in physiological conditions may depend on the behavioral task involved. Collectively, these findings shed new light on the functional role of GPe and suggest that it is a promising target for neuromodulatory restoration of motor deficits in PD.
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Kitagawa, Satoshi, Chunhua Tang, Miyuki Unekawa, Yohei Kayama, Jin Nakahara e Mamoru Shibata. "Sustained Effects of CGRP Blockade on Cortical Spreading Depolarization-Induced Alterations in Facial Heat Pain Threshold, Light Aversiveness, and Locomotive Activity in the Light Environment". International Journal of Molecular Sciences 23, n. 22 (9 novembre 2022): 13807. http://dx.doi.org/10.3390/ijms232213807.
Testo completoAbstract (sommario):
A migraine is clinically characterized by repeated headache attacks that entail considerable disability. Many patients with migraines experience postdrome, the symptoms of which include tiredness and photophobia. Calcitonin gene-related peptide (GGRP) is critically implicated in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, sensitizes the trigeminovascular system. In our previous study, CSD caused hypomotility in the light zone and tendency for photophobia at 72 h, at which time trigeminal sensitization had disappeared. We proposed that this CSD-induced disease state would be useful for exploring therapeutic strategies for migraine postdrome. In the present study, we observed that the CGRP receptor antagonist, olcegepant, prevented the hypomotility in the light zone and ameliorated light tolerability at 72 h after CSD induction. Moreover, olcegepant treatment significantly elevated the threshold for facial heat pain at 72 h after CSD. Our results raise the possibility that CGRP blockade may be efficacious in improving hypoactivity in the light environment by enhancing light tolerability during migraine postdrome. Moreover, our data suggest that the CGRP pathway may lower the facial heat pain threshold even in the absence of overt trigeminal sensitization, which provides an important clue to the potential mechanism whereby CGRP blockade confers migraine prophylaxis.
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Vila, Èlia, Raquel Pinacho, Roger Prades, Teresa Tarragó, Elena Castro, Eva Munarriz-Cuezva, J. Javier Meana et al. "Inhibition of Prolyl Oligopeptidase Restores Prohibitin 2 Levels in Psychosis Models: Relationship to Cognitive Deficits in Schizophrenia". International Journal of Molecular Sciences 24, n. 7 (23 marzo 2023): 6016. http://dx.doi.org/10.3390/ijms24076016.
Testo completoAbstract (sommario):
Cognitive impairment represents one of the core features of schizophrenia. Prolyl Oligopeptidase (POP) inhibition is an emerging strategy for compensating cognitive deficits in hypoglutamatergic states such as schizophrenia, although little is known about how POP inhibitors exert their pharmacological activity. The mitochondrial and nuclear protein Prohibitin 2 (PHB2) could be dysregulated in schizophrenia. However, altered PHB2 levels in schizophrenia linked to N-methyl-D-aspartate receptor (NMDAR) activity and cognitive deficits are still unknown. To shed light on this, we measured the PHB2 levels by immunoblot in a postmortem dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects, in the frontal pole of mice treated with the NMDAR antagonists phencyclidine and dizocilpine, and in rat cortical astrocytes and neurons treated with dizocilpine. Mice and cells were treated in combination with the POP inhibitor IPR19. The PHB2 levels were also analyzed by immunocytochemistry in rat neurons. The PHB2 levels increased in DLPFC in cases of chronic schizophrenia and were associated with cognitive impairments. NMDAR antagonists increased PHB2 levels in the frontal pole of mice and in rat astrocytes and neurons. High levels of PHB2 were found in the nucleus and cytoplasm of neurons upon NMDAR inhibition. IPR19 restored PHB2 levels in the acute NMDAR inhibition. These results show that IPR19 restores the upregulation of PHB2 in an acute NMDAR hypoactivity stage suggesting that the modulation of PHB2 could compensate NMDAR-dependent cognitive impairments in schizophrenia.
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Guilhot, Corentin, Théo Fovet, Pierre Delobel, Manon Dargegen, Bernard J. Jasmin, Thomas Brioche, Angèle Chopard e Guillaume Py. "Severe Muscle Deconditioning Triggers Early Extracellular Matrix Remodeling and Resident Stem Cell Differentiation into Adipocytes in Healthy Men". International Journal of Molecular Sciences 23, n. 10 (14 maggio 2022): 5489. http://dx.doi.org/10.3390/ijms23105489.
Testo completoAbstract (sommario):
Besides the loss of muscle mass and strength, increased intermuscular adipose tissue (IMAT) is now a well-recognized consequence of muscle deconditioning as experienced in prolonged microgravity. IMAT content may alter the muscle stem cell microenvironment. We hypothesized that extracellular matrix structure alterations and microenvironment remodeling induced by fast and severe muscle disuse could modulate fibro-adipogenic progenitor fate and behavior. We used the dry immersion (DI) model that rapidly leads to severe muscle deconditioning due to drastic hypoactivity. We randomly assigned healthy volunteers (n = 18 men) to the control group (only DI, n = 9; age = 33.8 ± 4) or to the DI + thigh cuff group (n = 9; age = 33.4 ± 7). Participants remained immersed in the supine position in a thermo-neutral water bath for 5 days. We collected vastus lateralis biopsies before (baseline) and after DI. 5 days of DI are sufficient to reduce muscle mass significantly, as indicated by the decreased myofiber cross-sectional area in vastus lateralis samples (−18% vs. baseline, p < 0.05). Early and late adipogenic differentiation transcription factors protein levels were upregulated. Platelet-derived growth Factors alpha (PDGFR⍺) protein level and PDGFR⍺-positive cells were increased after 5 days of DI. Extracellular matrix structure was prone to remodeling with an altered ECM composition with 4 major collagens, fibronectin, and Connective Tissue Growth Factor mRNA decreases (p < 0.001 vs. baseline). Wearing thigh cuffs did not have any preventive effect on the measured variable. Our results show that altered extracellular matrix structure and signaling pathways occur early during DI, a severe muscle wasting model, favoring fibro-adipogenic progenitor differentiation into adipocytes.
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Anglada-Huguet, Marta, Heike Endepols, Astrid Sydow, Ronja Hilgers, Bernd Neumaier, Alexander Drzezga, Senthilvelrajan Kaniyappan, Eckhard Mandelkow e Eva-Maria Mandelkow. "Reversal of Tau-Dependent Cognitive Decay by Blocking Adenosine A1 Receptors: Comparison of Transgenic Mouse Models with Different Levels of Tauopathy". International Journal of Molecular Sciences 24, n. 11 (25 maggio 2023): 9260. http://dx.doi.org/10.3390/ijms24119260.
Testo completoAbstract (sommario):
The accumulation of tau is a hallmark of several neurodegenerative diseases and is associated with neuronal hypoactivity and presynaptic dysfunction. Oral administration of the adenosine A1 receptor antagonist rolofylline (KW-3902) has previously been shown to reverse spatial memory deficits and to normalize the basic synaptic transmission in a mouse line expressing full-length pro-aggregant tau (TauΔK) at low levels, with late onset of disease. However, the efficacy of treatment remained to be explored for cases of more aggressive tauopathy. Using a combination of behavioral assays, imaging with several PET-tracers, and analysis of brain tissue, we compared the curative reversal of tau pathology by blocking adenosine A1 receptors in three mouse models expressing different types and levels of tau and tau mutants. We show through positron emission tomography using the tracer [18F]CPFPX (a selective A1 receptor ligand) that intravenous injection of rolofylline effectively blocks A1 receptors in the brain. Moreover, when administered to TauΔK mice, rolofylline can reverse tau pathology and synaptic decay. The beneficial effects are also observed in a line with more aggressive tau pathology, expressing the amyloidogenic repeat domain of tau (TauRDΔK) with higher aggregation propensity. Both models develop a progressive tau pathology with missorting, phosphorylation, accumulation of tau, loss of synapses, and cognitive decline. TauRDΔK causes pronounced neurofibrillary tangle assembly concomitant with neuronal death, whereas TauΔK accumulates only to tau pretangles without overt neuronal loss. A third model tested, the rTg4510 line, has a high expression of mutant TauP301L and hence a very aggressive phenotype starting at ~3 months of age. This line failed to reverse pathology upon rolofylline treatment, consistent with a higher accumulation of tau-specific PET tracers and inflammation. In conclusion, blocking adenosine A1 receptors by rolofylline can reverse pathology if the pathological potential of tau remains below a threshold value that depends on concentration and aggregation propensity.
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Kustubayeva, Almira, Altyngul Kamzanova, Sandugash Kudaibergenova, Veronika Pivkina e Gerald Matthews. "Major Depression and Brain Asymmetry in a Decision-Making Task with Negative and Positive Feedback". Symmetry 12, n. 12 (21 dicembre 2020): 2118. http://dx.doi.org/10.3390/sym12122118.
Testo completoAbstract (sommario):
Depressed patients are characterized by hypoactivity of the left and hyperactivity of the right frontal areas during the resting state. Depression is also associated with impaired decision-making, which reflects multiple cognitive, affective, and attentional processes, some of which may be lateralized. The aim of this study was to investigate brain asymmetry during a decision-making task performed in negative and positive feedback conditions in patients with Major Depressive Disorder (MDD) in comparison to healthy control participants. The electroencephalogram (EEG) was recorded from 60 MDD patients and 60 healthy participants while performing a multi-stage decision-making task. Frontal, central, and parietal alpha asymmetry were analyzed with EEGlab/ERPlab software. Evoked potential responses (ERPs) showed general lateralization suggestive of an initial right dominance developing into a more complex pattern of asymmetry across different scalp areas as information was processed. The MDD group showed impaired mood prior to performance, and decreased confidence during performance in comparison to the control group. The resting state frontal alpha asymmetry showed lateralization in the healthy group only. Task-induced alpha power and ERP P100 and P300 amplitudes were more informative biomarkers of depression during decision making. Asymmetry coefficients based on task alpha power and ERP amplitudes showed consistency in the dynamical changes during the decision-making stages. Depression was characterized by a lack of left dominance during the resting state and left hypoactivity during the task baseline and subsequent decision-making process. Findings add to understanding of the functional significance of lateralized brain processes in depression.
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Scheibli, Leonie, Tabita Elsenhans, Harald Wolf, Torben Stemme e Sarah Elisabeth Pfeffer. "Influence of the pesticide flupyradifurone on mobility and physical condition of larval green lacewings". Scientific Reports 13, n. 1 (13 novembre 2023). http://dx.doi.org/10.1038/s41598-023-46135-7.
Testo completoAbstract (sommario):
AbstractGlobal pesticide use in agriculture is one reason for the rapid insect decline in recent years. The relatively new pesticide flupyradifurone is neurotoxic to pest insects but considered harmless to bees according to previous risk assessments. With this study, we aim to investigate lethal and sublethal effects of flupyradifurone on larvae of the beneficial arthropod Chrysoperla carnea. We treated the animals orally with field-realistic concentrations of flupyradifurone and examined lethality as well as effects on condition, mobility and locomotion. For the lethal dose 50, we determined a value of > 120–200 ng/mg (corresponding to a mean amount of 219 ng/larva) after 168 h. Abnormal behaviors such as trembling and comatose larvae were observed even at the lowest concentration applied (> 0–20 ng/mg, 59 ng/larva). Mobility analysis showed impaired activity patterns, resulting in acute hypoactivity at all pesticide concentrations and time-delayed hyperactivity in larvae treated with > 40–60 ng/mg (100 ng/larva) and > 80–100 ng/mg (120 ng/larva), respectively. Even locomotion as a fundamental behavioral task was negatively influenced throughout larval development. In conclusion, our results demonstrate that flupyradifurone impacts life and survival of lacewing larvae and may pose—despite its status as bee-friendly—a major threat to insect fauna and environment.
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Schwarck, Svenja, Nancy Busse, Gabriel Ziegler, Wenzel Glanz, Andreas Becke e Emrah Düzel. "Heart Rate Variability During Physical Exercise Is Associated With Improved Cognitive Performance in Alzheimer's Dementia Patients—A Longitudinal Feasibility Study". Frontiers in Sports and Active Living 3 (15 luglio 2021). http://dx.doi.org/10.3389/fspor.2021.684089.
Testo completoAbstract (sommario):
Heart rate variability (HRV) rapidly gains attention as an important marker of cardiovascular autonomic modulation. Moreover, there is evidence for a link between the autonomic deficit measurable by reduced HRV and the hypoactivity of the cholinergic system, which is prominently affected in Alzheimer's disease (AD). Despite the positive influence of physical exercise on cognition and its promising association with HRV, previous studies did not explore the effect of long-term physical exercise in older adults with AD. Taking advantage of a longitudinal study we analyzed the effect of a 20-week dual task training regime (3 × 15-min per week) on the vagal mediated HRV index RMSSD (root mean square of successive RR interval differences) during physical exercise and the short-term memory performance in a AD cohort (N = 14). Each training contained physical exercise on a bicycle ergometer while memorizing 30 successively presented pictures as well as the associated post-exercise picture recognition memory test. Linear-mixed modeling revealed that HRV-RMSSD significantly increased over the intervention time. Moreover, the reaction time in the picture recognition task decreased while the accuracy remained stable. Furthermore, a significantly negative relationship between increased fitness measured by HRV-RMSSD and decreased reaction time was observed. This feasibility study points to the positive effects of a dual task regime on physical and cognitive fitness in a sample with impaired cognitive performance. Beyond this, the results show that the responsiveness of parasympathetic system as measured with HRV can be improved in patients with dementia.
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Mahmood, Zeid, Anette Davidsson, Eva Olsson, Per Leanderson, Anna K. Lundberg e Lena Jonasson. "The effect of acute exercise on interleukin-6 and hypothalamic–pituitary–adrenal axis responses in patients with coronary artery disease". Scientific Reports 10, n. 1 (dicembre 2020). http://dx.doi.org/10.1038/s41598-020-78286-2.
Testo completoAbstract (sommario):
AbstractVulnerability to stress-induced inflammation has been linked to a dysfunctional hypothalamus–pituitary–adrenal (HPA) axis. In the present study, patients with known or suspected coronary artery disease (CAD) were assessed with respect to inflammatory and HPA axis response to acute physical exercise. An exercise stress test was combined with SPECT myocardial perfusion imaging. Plasma and saliva samples were collected before and 30 min after exercise. Interleukin (IL)-6 and adrenocorticotropic hormone (ACTH) were measured in plasma, while cortisol was measured in both plasma and saliva. In total, 124 patients were included of whom 29% had a prior history of CAD and/or a myocardial perfusion deficit. The levels of exercise intensity and duration were comparable in CAD and non-CAD patients. However, in CAD patients, IL-6 increased after exercise (p = 0.019) while no differences were seen in HPA axis variables. Conversely, patients without CAD exhibited increased levels of ACTH (p = 0.003) and cortisol (p = 0.004 in plasma, p = 0.006 in saliva), but no change in IL-6. We conclude that the IL-6 response to acute physical exercise is exaggerated in CAD patients and may be out of balance due to HPA axis hypoactivity. It remains to be further investigated whether this imbalance is a potential diagnostic and therapeutic target in CAD.
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Schmechel, Fernanda Rossi. "Major evidence of clinical studies on the triad gut microbiota, ubiquinone and physical exercise: a systematic review". International Journal of Nutrology 16, n. 2 (17 marzo 2023). http://dx.doi.org/10.54448/ijn23201.
Testo completoAbstract (sommario):
Introduction: In the scenario of sports practices, the human gut microbiota is currently the focus of convergent interest in many diseases and sports performance. Sports performance studies have also shown interesting and promising results. Supplementation with certain antioxidants such as ubiquinone [Coenzyme Q10 (CoQ10)] is important for physically active individuals to speed recovery from fatigue and prevent exercise damage. Objective: It was to demonstrate the influence of the gut microbiota and ubiquinone on the performance of athletes. Methods: The systematic review rules of the PRISMA Platform were followed. The research was carried out from September to November 2022 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: 104 articles were found. A total of 54 articles were evaluated and 27 were included in this systematic review. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 13 studies with a high risk of bias and 27 studies that did not meet GRADE. Most studies showed homogeneity in their results, with X 2 =97.2% >50%. The composition and activity of the gut microbiota are influenced by many different factors, such as diet and physical activity. Cumulative data indicate that gut bacteria are sensitive to modulation by physical activity, as demonstrated by studies using models of training and hypoactivity. Supplementation with the antioxidant Coenzyme Q10 is important for physically active individuals to accelerate recovery from fatigue and prevent damage caused by exercise, in addition to optimizing training and improving sports performance. Clinical studies have shown that in physical fatigue concerning physical exercise, patients have low plasma concentrations of Coenzyme Q10.
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Miller, Melissa C., Steven K. Shapiro e Stephen P. Becker. "Examining Cognitive Disengagement Syndrome in Relation to Social Problem Solving in Young Adults". Journal of Attention Disorders, 15 aprile 2024. http://dx.doi.org/10.1177/10870547241247176.
Testo completoAbstract (sommario):
Objective: Cognitive disengagement syndrome (CDS), previously referred to as sluggish cognitive tempo (SCT), is characterized by symptoms such as excessive daydreaming, mental confusion, and hypoactivity. CDS symptoms are associated with emotional, social, and daily life impairments. The way in which one solves problems in their daily life is associated with experiences of further problems, such that maladaptive problem-solving can lead to further physical and psychological problems. However, there is limited information on how CDS symptoms are associated with problem solving. The current study examined CDS symptoms in relation to different social problem solving approaches. Method: A total of 280 college students (ages 18–23 years; 77.9% female) completed measures of psychopathology symptoms and social problem solving. Results: Above and beyond ADHD and internalizing symptoms, CDS symptoms were independently associated with negative problem orientation and avoidance style domains of maladaptive problem solving. Conclusion: Findings indicate that CDS symptoms are related to specific difficulties with social problem solving. CDS symptoms may lead to difficulties attending to problems or working through relevant steps needed to identify solutions for the problem, which may then lead to avoidance and social withdrawal. Longitudinal research is needed to evaluate maladaptive problem solving as a potential mechanism in the association between CDS, social withdrawal, and internalizing symptoms.
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Rösch, Sarah A., Lennart Wünsche, Carsten Thiele, Therese Reinstaller, Tino Zähle, Kathrin Schag, Katrin E. Giel, Christian Plewnia, Johann Steiner e Florian Junne. "Enhancing the outcomes of bariatric surgery with inhibitory control training, electrical brain stimulation and psychosocial aftercare: a pilot study protocol". Journal of Eating Disorders 12, n. 1 (9 dicembre 2024). https://doi.org/10.1186/s40337-024-01160-3.
Testo completoAbstract (sommario):
Abstract Background Notwithstanding the documented short- and long-term weight loss and remission of physical and mental diseases following bariatric surgery, a significant proportion of patients fail to respond (fully) to treatment in terms of physical and mental health improvement. Mounting evidence links food-specific impulsivity, prefrontal cortex (PFC) hypoactivity and disrupted hormone secretion in bariatric surgery candidates to poorer post-surgical health outcomes. Neuromodulatory treatments like transcranial direct current stimulation (tDCS) uniquely target these neurobehavioral impairments. We present a pilot study protocol offering tDCS combined with an inhibitory control training and a structured psychosocial intervention to patients after bariatric surgery. Methods A total of N = 20 patients are randomized to 6 sessions of verum or sham tDCS over the PFC, combined with an individualized food-specific inhibitory control training and a structured psychosocial intervention within 18 months after bariatric surgery (t0). Beyond acceptability, feasibility and satisfaction of the intervention, effects of verum versus sham tDCS on food-specific impulsivity and on secondary outcomes quality of life, general impulsivity and psychopathology, food-related cravings, eating disorder psychopathology, weight trajectory and endocrine markers are assessed 4 weeks (t1) and 3 months after the intervention (t2). Discussion Results will provide information on the potential of combining tDCS with an inhibitory control training and a structured psychosocial intervention to enhance physical and mental outcomes after bariatric surgery. The present study may guide the development of future research with regard to tDCS as a brain-based intervention and of future post-surgical clinical programs, paving the way for randomized-controlled trials in larger samples. Trial registration The trial was prospectively registered on July 8, 2024, under the registration number DRKS00034620 in the German Clinical Trials Register (https://drks.de/search/de/trial/DRKS00034620).
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Nigro, Sarah. "A - 145 Cognitive Disengagement Syndrome in ALL Survivor". Archives of Clinical Neuropsychology, 12 settembre 2024. http://dx.doi.org/10.1093/arclin/acae067.159.
Testo completoAbstract (sommario):
Abstract Objective Cognitive disengagement syndrome (CDS), previously known as sluggish cognitive tempo (SCT), presents with symptoms like mind-wandering, hypoactivity, and mental fogginess. There is a relatively high prevalence (23.7%) of CDS in survivors of acute lymphoblastic leukemia (ALL), although the neuropathology remains poorly understood, potentially involving autonomic nervous system dysfunction. Cognitive late effects, including slowed speed, inattention and executive dysfunction can occur post-cancer treatment. This case highlights the need for regular assessment of CDS, particularly in the pediatric cancer population. Given the symptom overlap it is important to discuss onset, duration, and variability of symptom presentation to rule-in/out the role of cognitive late effects. Method “Alex,” a 14-year-old, B cell ALL survivor, was struggling academically nine years post-treatment. She and parents reported slowness, fatigue, trouble concentrating, and social withdrawal, despite medical stability. She received two years of psychotherapy for anxiety and depression without improvement. Results Alex had average intellectual and cognitive functioning, with mild executive dysfunction. Despite reported slowness in daily activities, processing speed was average. Parent and self-report forms indicated significant problems with executive functioning, somatic symptoms, and inattention. Parents indicated significant symptoms on the SCT scale. Alex’s cognitive profile suggested ADHD-I with features consistent with CDS. Conclusions Discrepancies between testing scores and daily life challenges were inconsistent with cognitive late effects. Her physical symptoms (e.g., fatigue, social withdrawal) did not improve with mood as expected with depression. Identifying these discrepancies and symptom timeline was crucial in diagnosing CDS and guiding interventions, leading to a sense of relief and direction for Alex and her family.
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Wang, Lun, Min Gao, Qinglong Wang, Liyuan Sun, Muhammad Younus, Sixing Ma, Can Liu et al. "Cocaine induces locomotor sensitization through a dopamine-dependent VTA-mPFC-FrA cortico-cortical pathway in male mice". Nature Communications 14, n. 1 (21 marzo 2023). http://dx.doi.org/10.1038/s41467-023-37045-3.
Testo completoAbstract (sommario):
AbstractAs a central part of the mammalian brain, the prefrontal cortex (PFC) has been implicated in regulating cocaine-induced behaviors including compulsive seeking and reinstatement. Although dysfunction of the PFC has been reported in animal and human users with chronic cocaine abuse, less is known about how the PFC is involved in cocaine-induced behaviors. By using two-photon Ca2+ imaging to simultaneously record tens of intact individual networking neurons in the frontal association cortex (FrA) in awake male mice, here we report that a systematic acute cocaine exposure decreased the FrA neural activity in mice, while the chemogenetic intervention blocked the cocaine-induced locomotor sensitization. The hypoactivity of FrA neurons was critically dependent on both dopamine transporters and dopamine transmission in the ventromedial PFC (vmPFC). Both dopamine D1R and D2R neurons in the vmPFC projected to and innervated FrA neurons, the manipulation of which changed the cocaine-induced hypoactivity of the FrA and locomotor sensitization. Together, this work demonstrates acute cocaine-induced hypoactivity of FrA neurons in awake mice, which defines a cortico-cortical projection bridging dopamine transmission and cocaine sensitization.
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Huang, Cheng, Haiyan Luo, Baitao Zeng, Chuanxin Feng, Jia Chen, Huizhen Yuan, Shuhui Huang, Bicheng Yang, Yongyi Zou e Yanqiu Liu. "Identification of two novel and one rare mutation in DYRK1A and prenatal diagnoses in three Chinese families with intellectual Disability-7". Frontiers in Genetics 14 (20 dicembre 2023). http://dx.doi.org/10.3389/fgene.2023.1290949.
Testo completoAbstract (sommario):
Background and purpose: Intellectual disability-7 (MRD7) is a subtype disorder of intellectual disability (MRD) involving feeding difficulties, hypoactivity, and febrile seizures at an age of early onset, then progressive intellectual and physical development deterioration. We purposed to identify the underlying causative genetic factors of three individuals in each Chinese family who presented with symptoms of intellectual disability and facial dysmorphic features. We provided prenatal diagnosis for the three families and genetic counseling for the prevention of this disease.Methods: We collected retrospective clinical diagnostic evidence for the three probands in our study, which included magnetic resonance imaging (MRI), computerized tomography (CT), electroencephalogram (EEG), and intelligence tests for the three probands in our study. Genetic investigation of the probands and their next of kin was performed by Trio-whole exome sequencing (WES). Sanger sequencing or quantitative PCR technologies were then used as the next step to verify the variants confirmed with Trio-WES for the three families. Moreover, we performed amniocentesis to explore the state of the three pathogenic variants in the fetuses by prenatal molecular genetic diagnosis at an appropriate gestational period for the three families.Results: The three probands and one fetus were clinically diagnosed with microcephaly and exhibited intellectual developmental disability, postnatal feeding difficulties, and facial dysmorphic features. Combining probands’ clinical manifestations, Trio-WES uncovered the three heterozygous variants in DYRK1A: a novel variant exon3_exon4del p.(Gly4_Asn109del), a novel variant c.1159C>T p.(Gln387*), and a previously presented but rare pathogenic variant c.1309C>T p.(Arg437*) (NM_001396.5) in three families, respectively. In light of the updated American College of Medical Genetic and Genomics (ACMG) criterion, the variant of exon3_exon4del and c.1159C>T were both classified as likely pathogenic (PSV1+PM6), while c1309C>T was identified as pathogenic (PVS1+PS2_Moderate+PM2). Considering clinical features and molecular testimony, the three probands were confirmed diagnosed with MRD7. These three discovered variants were considered as the three causal mutations for MRD7. Prenatal diagnosis detected the heterozygous dominant variant of c.1159C>T p.(Gln387*) in one of the fetuses, indicating a significant probability of MRD7, subsequently the gestation was intervened by the parents’ determination and professional obstetrical operation. On the other side, prenatal molecular genetic testing revealed wild-type alleles in the other two fetuses, and their parents both decided to sustain the gestation.Conclusion: We identified two novel and one rare mutation in DYRK1A which has broadened the spectrum of DYRK1A and provided evidence for the diagnosis of MRD7 at the molecular level. Besides, this study has supported the three families with MRD7 to determine the causative genetic factors efficiently and provide concise genetic counseling for the three families by using Trio-WES technology.
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Lia, Annamaria, Gabriele Sansevero, Angela Chiavegato, Miriana Sbrissa, Diana Pendin, Letizia Mariotti, Tullio Pozzan et al. "Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer’s disease". Nature Communications 14, n. 1 (22 marzo 2023). http://dx.doi.org/10.1038/s41467-023-37240-2.
Testo completoAbstract (sommario):
AbstractCalcium dynamics in astrocytes represent a fundamental signal that through gliotransmitter release regulates synaptic plasticity and behaviour. Here we present a longitudinal study in the PS2APP mouse model of Alzheimer’s disease (AD) linking astrocyte Ca2+ hypoactivity to memory loss. At the onset of plaque deposition, somatosensory cortical astrocytes of AD female mice exhibit a drastic reduction of Ca2+ signaling, closely associated with decreased endoplasmic reticulum Ca2+ concentration and reduced expression of the Ca2+ sensor STIM1. In parallel, astrocyte-dependent long-term synaptic plasticity declines in the somatosensory circuitry, anticipating specific tactile memory loss. Notably, we show that both astrocyte Ca2+ signaling and long-term synaptic plasticity are fully recovered by selective STIM1 overexpression in astrocytes. Our data unveil astrocyte Ca2+ hypoactivity in neocortical astrocytes as a functional hallmark of early AD stages and indicate astrocytic STIM1 as a target to rescue memory deficits.
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Amano, Izuki, Ayane Ninomiya, Reika Kawabata-Iwakawa, Megan Ritter, Anthony Hollenberg e Noriyuki Koibuchi. "Roles of the nuclear receptor corepressor 1 (NCoR1) and the silencing mediator of retinoid and thyroid hormone receptors (SMRT) in the developing brain". Physiology 38, S1 (maggio 2023). http://dx.doi.org/10.1152/physiol.2023.38.s1.5732054.
Testo completoAbstract (sommario):
The nuclear receptor corepressor 1 (NCoR1) and the silencing mediator of retinoic acid and thyroid hormone (SMRT) are critical coregulators of the nuclear receptor (e.g., thyroid hormone receptors and retinoic acid receptors), mediating transcriptional repression via histone deacetylation. Although they are highly homologous and have similar nuclear receptor interaction domains, they have different roles in different organs. Recently, de novo genetic variants in nuclear corepressors were found in pediatric patients with neurodevelopmental disorders. Thus, we generated the mouse models to understand the role of NCOR1 and SMRT in the central nervous system. We used the mice with conditional NCoR1 or SMRT (NCoR1lox/lox or SMRTlox/lox) alleles in combination with the mice that express Cre recombinase in a neuronal specific fashion (Snap25-Ires2-Cre). First, we performed a battery of behavioral tests to screen behavioral phenotype of mice. We found that hypoactivity, social deficits, and mild anxiety in neuronal specific NCoR1 or SMRT KO mice. In addition, NCoR1 KO mice showed high learning abilities in pairwise visual discrimination task. Next, we performed RNA-sequencing analysis with amygdala from postnatal day 21 to investigate gene expression mediated by NCoR1 and SMRT. We found that 449 genes were upregulated by SMRT deletion, whereas only 8 genes were upregulated by NCoR1 deletion. Overall, our data demonstrate for the first time that NCoR1 and SMRT have separate functions in the central nervous system. JSPS Grant-in-Aid for Early-Career Scientists 19K16486, 21K15340 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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Fang, Li-Pao, Na Zhao, Laura C. Caudal, Hsin-Fang Chang, Renping Zhao, Ching-Hsin Lin, Nadine Hainz et al. "Impaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior". Nature Communications 13, n. 1 (16 marzo 2022). http://dx.doi.org/10.1038/s41467-022-29020-1.
Testo completoAbstract (sommario):
AbstractCortical neural circuits are complex but very precise networks of balanced excitation and inhibition. Yet, the molecular and cellular mechanisms that form the balance are just beginning to emerge. Here, using conditional γ-aminobutyric acid receptor B1- deficient mice we identify a γ-aminobutyric acid/tumor necrosis factor superfamily member 12-mediated bidirectional communication pathway between parvalbumin-positive fast spiking interneurons and oligodendrocyte precursor cells that determines the density and function of interneurons in the developing medial prefrontal cortex. Interruption of the GABAergic signaling to oligodendrocyte precursor cells results in reduced myelination and hypoactivity of interneurons, strong changes of cortical network activities and impaired social cognitive behavior. In conclusion, glial transmitter receptors are pivotal elements in finetuning distinct brain functions.
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Jia, Tao, Ying-Di Wang, Jing Chen, Xue Zhang, Jun-Li Cao, Cheng Xiao e Chunyi Zhou. "A nigro–subthalamo–parabrachial pathway modulates pain-like behaviors". Nature Communications 13, n. 1 (15 dicembre 2022). http://dx.doi.org/10.1038/s41467-022-35474-0.
Testo completoAbstract (sommario):
AbstractThe basal ganglia including the subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) are involved in pain-related responses, but how they regulate pain processing remains unknown. Here, we identify a pathway, consisting of GABAergic neurons in the SNr (SNrGABA) and glutamatergic neurons in the STN (STNGlu) and the lateral parabrachial nucleus (LPBGlu), that modulates acute and persistent pain states in both male and female mice. The activity of STN neurons was enhanced in acute and persistent pain states. This enhancement was accompanied by hypoactivity in SNrGABA neurons and strengthening of the STN–LPB glutamatergic projection. Reversing the dysfunction in the SNrGABA-STNGlu-LPBGlu pathway attenuated activity of LPBGlu neurons and mitigated pain-like behaviors. Therefore, the SNrGABA-STNGlu-LPBGlu pathway regulates pathological pain and is a potential target for pain management.
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Rogalski, Aymeric, S. W. A. Himaya e Richard J. Lewis. "Coordinated adaptations define the ontogenetic shift from worm- to fish-hunting in a venomous cone snail". Nature Communications 14, n. 1 (13 giugno 2023). http://dx.doi.org/10.1038/s41467-023-38924-5.
Testo completoAbstract (sommario):
AbstractMarine cone snails have attracted researchers from all disciplines but early life stages have received limited attention due to difficulties accessing or rearing juvenile specimens. Here, we document the culture of Conus magus from eggs through metamorphosis to reveal dramatic shifts in predatory feeding behaviour between post-metamorphic juveniles and adult specimens. Adult C. magus capture fish using a set of paralytic venom peptides combined with a hooked radular tooth used to tether envenomed fish. In contrast, early juveniles feed exclusively on polychaete worms using a unique “sting-and-stalk” foraging behaviour facilitated by short, unbarbed radular teeth and a distinct venom repertoire that induces hypoactivity in prey. Our results demonstrate how coordinated morphological, behavioural and molecular changes facilitate the shift from worm- to fish-hunting in C. magus, and showcase juvenile cone snails as a rich and unexplored source of novel venom peptides for ecological, evolutionary and biodiscovery studies.
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Yang, Soo Hyun, Esther Yang, Jaekwang Lee, Jin Yong Kim, Hyeijung Yoo, Hyung Sun Park, Jin Taek Jung et al. "Neural mechanism of acute stress regulation by trace aminergic signalling in the lateral habenula in male mice". Nature Communications 14, n. 1 (27 aprile 2023). http://dx.doi.org/10.1038/s41467-023-38180-7.
Testo completoAbstract (sommario):
AbstractStress management is necessary for vertebrate survival. Chronic stress drives depression by excitation of the lateral habenula (LHb), which silences dopaminergic neurons in the ventral tegmental area (VTA) via GABAergic neuronal projection from the rostromedial tegmental nucleus (RMTg). However, the effect of acute stress on this LHb-RMTg-VTA pathway is not clearly understood. Here, we used fluorescent in situ hybridisation and in vivo electrophysiology in mice to show that LHb aromatic l-amino acid decarboxylase-expressing neurons (D-neurons) are activated by acute stressors and suppress RMTg GABAergic neurons via trace aminergic signalling, thus activating VTA dopaminergic neurons. We show that the LHb regulates RMTg GABAergic neurons biphasically under acute stress. This study, carried out on male mice, has elucidated a molecular mechanism in the efferent LHb-RMTg-VTA pathway whereby trace aminergic signalling enables the brain to manage acute stress by preventing the hypoactivity of VTA dopaminergic neurons.