Academic literature on the topic 'Endocannabinois'
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Journal articles on the topic "Endocannabinois"
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Fonseca, B. M., G. Correia-da-Silva, M. Almada, M. A. Costa, and N. A. Teixeira. "The Endocannabinoid System in the Postimplantation Period: A Role during Decidualization and Placentation." International Journal of Endocrinology 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/510540.
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Although the detrimental effects of cannabis consumption during gestation are known for years, the vast majority of studies established a link between cannabis consumption and foetal development. The complex maternal-foetal interrelationships within the placental bed are essential for normal pregnancy, and decidua definitively contributes to the success of this process. Nevertheless, the molecular signalling network that coordinates strategies for successful decidualization and placentation are not well understood. The discovery of the endocannabinoid system highlighted new signalling mediators in various physiological processes, including reproduction. It is known that endocannabinoids present regulatory functions during blastocyst development, oviductal transport, and implantation. In addition, all the endocannabinoid machinery was found to be expressed in decidual and placental tissues. Additionally, endocannabinoid’s plasmatic levels were found to fluctuate during normal gestation and to induce decidual cell death and disturb normal placental development. Moreover, aberrant endocannabinoid signalling during the period of placental development has been associated with pregnancy disorders. It indicates the existence of a possible regulatory role for these molecules during decidualization and placentation processes, which are known to be particularly vulnerable. In this review, the influence of the endocannabinoid system in these critical processes is explored and discussed.
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Lee, Yunna, Jeongbin Jo, Hae Young Chung, Charalabos Pothoulakis, and Eunok Im. "Endocannabinoids in the gastrointestinal tract." American Journal of Physiology-Gastrointestinal and Liver Physiology 311, no. 4 (October 1, 2016): G655—G666. http://dx.doi.org/10.1152/ajpgi.00294.2015.
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The endocannabinoid system mainly consists of endogenously produced cannabinoids (endocannabinoids) and two G protein-coupled receptors (GPCRs), cannabinoid receptors 1 and 2 (CB1 and CB2). This system also includes enzymes responsible for the synthesis and degradation of endocannabinoids and molecules required for the uptake and transport of endocannabinoids. In addition, endocannabinoid-related lipid mediators and other putative endocannabinoid receptors, such as transient receptor potential channels and other GPCRs, have been identified. Accumulating evidence indicates that the endocannabinoid system is a key modulator of gastrointestinal physiology, influencing satiety, emesis, immune function, mucosal integrity, motility, secretion, and visceral sensation. In light of therapeutic benefits of herbal and synthetic cannabinoids, the vast potential of the endocannabinoid system for the treatment of gastrointestinal diseases has been demonstrated. This review focuses on the role of the endocannabinoid system in gut homeostasis and in the pathogenesis of intestinal disorders associated with intestinal motility, inflammation, and cancer. Finally, links between gut microorganisms and the endocannabinoid system are briefly discussed.
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Suchopár, Josef, Zdeněk Laštůvka, Simona Mašková, Miroslava Alblová, and Antonín Pařízek. "Endocannabinoids." Česká gynekologie 86, no. 6 (December 21, 2021): 414–20. http://dx.doi.org/10.48095/cccg2021414.
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Objective: Overview of current knowledge in the field of the endocannabinoid system with emphasis on the relationships between endocannabinoids and exocannabinoids. The endocannabinoid system consists of cannabinoid receptors 1 and 2, ligands of these receptors, especially two "classical" endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoyl-glycerol. Transport systems that ensure the entry of endocannabinoids into cells, where they are degraded by fatty acid amide hydrolase or monoacylglycerol lipase. The endocannabinoid system is a signaling pathway for the regulation of a number of physiological or pathological conditions. So far, it is one of the less explored ways of regulation, as evidenced by the recent explosive increase in the number of published works. Dysregulation of endocannabinoid systems is a possible cause of many diseases. It can occur both in the genetic polymorphism of its individual components, but also in therapy with certain drugs or natural substances, typically cannabinoids. Due to the wide overlap of the regulation of physiological functions by the endocannabinoid system, a considerable number of drugs are being developed, the aim of which is to correct the dysregulation of the endocannabinoid system. Conclusion: The endocannabinoid system is one of the most important regulatory systems with a very broad intervention in physiological and pathological conditions. The resulting specific regulations intersect the interplay of many enzymes involved in the production and degradation of endocannabinoids, transport systems involved in the entry of endocannabinoids into cells, cannabinoid receptors and exogenous cannabinoids, or natural substances acting at various sites in the endocannabinoid system. Knowledge in this area can contribute to improving health care and increasing the safety of its provision. Key words: endocannabinoids – anandamide – 2-arachidoyl glycerol – cannabinoid receptor – fatty acid binding proteins – fatty acid amide hydrolases – lipase for monoacylglycerols – cannabinoids
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Ayakannu, Thangesweran, Anthony H. Taylor, Timothy H. Marczylo, Jonathon M. Willets, and Justin C. Konje. "The Endocannabinoid System and Sex Steroid Hormone-Dependent Cancers." International Journal of Endocrinology 2013 (2013): 1–14. http://dx.doi.org/10.1155/2013/259676.
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The “endocannabinoid system (ECS)” comprises the endocannabinoids, the enzymes that regulate their synthesis and degradation, the prototypical cannabinoid receptors (CB1 and CB2), some noncannabinoid receptors, and an, as yet, uncharacterised transport system. Recent evidence suggests that both cannabinoid receptors are present in sex steroid hormone-dependent cancer tissues and potentially play an important role in those malignancies. Sex steroid hormones regulate the endocannabinoid system and the endocannabinoids prevent tumour development through putative protective mechanisms that prevent cell growth and migration, suggesting an important role for endocannabinoids in the regulation of sex hormone-dependent tumours and metastasis. Here, the role of the endocannabinoid system in sex steroid hormone-dependent cancers is described and the potential for novel therapies assessed.
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Keereetaweep, Jantana, and Kent D. Chapman. "Lipidomic Analysis of Endocannabinoid Signaling: Targeted Metabolite Identification and Quantification." Neural Plasticity 2016 (2016): 1–13. http://dx.doi.org/10.1155/2016/2426398.
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The endocannabinoidsN-arachidonoylethanolamide (or anandamide, AEA) and 2-arachidonoylglycerol (2-AG) belong to the larger groups ofN-acylethanolamines (NAEs) and monoacylglycerol (MAG) lipid classes, respectively. They are biologically active lipid molecules that activate G-protein-coupled cannabinoid receptors found in various organisms. After AEA and 2-AG were discovered in the 1990s, they have been extensively documented to have a broad range of physiological functions. Along with AEA, several NAEs, for example,N-palmitoylethanolamine (PEA),N-stearoylethanolamine (SEA), andN-oleoylethanolamine (OEA) are also present in tissues, usually at much larger concentrations than AEA. Any perturbation that involves the endocannabinoid pathway may subsequently alter basal level or metabolism of these lipid mediators. Further, the altered levels of these molecules often reflect pathological conditions associated with tissue damage. Robust and sensitive methodologies to analyze these lipid mediators are essential to understanding how they act as endocannabinoids. The recent advances in mass spectrometry allow researchers to develop lipidomics approaches and several methodologies have been proposed to quantify endocannabinoids in various biological systems.
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Chan, Hsiu-Wen, Natalie C. McKirdy, Hassendrini N. Peiris, Gregory E. Rice, and Murray D. Mitchell. "The role of endocannabinoids in pregnancy." REPRODUCTION 146, no. 3 (September 2013): R101—R109. http://dx.doi.org/10.1530/rep-12-0508.
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Endocannabinoids are a family of lipid signalling molecules. As with prostaglandins (PGs), endocannabinoids are derived from polyunsaturated fatty acids and affect cell function via receptor-mediated mechanisms. They also bind to PG receptors, although at a lower affinity. The endocannabinoid network is regulated in pregnancy from embryo development to labour onset. Even small changes in endocannabinoid exposure can retard embryo development and affect implantation success. There is now compelling evidence that aberrant expression of factors involved in the endocannabinoid pathway in the placenta and circulating lymphocytes results in spontaneous miscarriage and poor pregnancy outcomes. It is likely that competition between endocannabinoids, PGs and other similar lipids ultimately determines how phospholipid/fatty acid substrates are metabolised and, thus, the balance between the uterotonic and tocolytic activities. We, therefore, hypothesise that endocannabinoid profiles may be used as a biomarker to predict and/or identify spontaneous labour onset.
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Friend, Lindsey, Ryan Williamson, Collin Merrill, Scott Newton, Michael Christensen, Jake Petersen, Bridget Wu, Isaac Ostlund, and Jeffrey Edwards. "Hippocampal Stratum Oriens Somatostatin-Positive Cells Undergo CB1-Dependent Long-Term Potentiation and Express Endocannabinoid Biosynthetic Enzymes." Molecules 24, no. 7 (April 3, 2019): 1306. http://dx.doi.org/10.3390/molecules24071306.
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The hippocampus is thought to encode information by altering synaptic strength via synaptic plasticity. Some forms of synaptic plasticity are induced by lipid-based endocannabinoid signaling molecules that act on cannabinoid receptors (CB1). Endocannabinoids modulate synaptic plasticity of hippocampal pyramidal cells and stratum radiatum interneurons; however, the role of endocannabinoids in mediating synaptic plasticity of stratum oriens interneurons is unclear. These feedback inhibitory interneurons exhibit presynaptic long-term potentiation (LTP), but the exact mechanism is not entirely understood. We examined whether oriens interneurons produce endocannabinoids, and whether endocannabinoids are involved in presynaptic LTP. Using patch-clamp electrodes to extract single cells, we analyzed the expression of endocannabinoid biosynthetic enzyme mRNA by reverse transcription and then real-time PCR (RT-PCR). The cellular expression of calcium-binding proteins and neuropeptides were used to identify interneuron subtype. RT-PCR results demonstrate that stratum oriens interneurons express mRNA for both endocannabinoid biosynthetic enzymes and the type I metabotropic glutamate receptors (mGluRs), necessary for endocannabinoid production. Immunohistochemical staining further confirmed the presence of diacylglycerol lipase alpha, an endocannabinoid-synthesizing enzyme, in oriens interneurons. To test the role of endocannabinoids in synaptic plasticity, we performed whole-cell experiments using high-frequency stimulation to induce long-term potentiation in somatostatin-positive cells. This plasticity was blocked by AM-251, demonstrating CB1-dependence. In addition, in the presence of a fatty acid amide hydrolase inhibitor (URB597; 1 µM) and MAG lipase inhibitor (JZL184; 1 µM) that increase endogenous anandamide and 2-arachidonyl glycerol, respectively, excitatory current responses were potentiated. URB597-induced potentiation was blocked by CB1 antagonist AM-251 (2 µM). Collectively, this suggests somatostatin-positive oriens interneuron LTP is CB1-dependent.
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Kano, Masanobu, Takako Ohno-Shosaku, Yuki Hashimotodani, Motokazu Uchigashima, and Masahiko Watanabe. "Endocannabinoid-Mediated Control of Synaptic Transmission." Physiological Reviews 89, no. 1 (January 2009): 309–80. http://dx.doi.org/10.1152/physrev.00019.2008.
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The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB1 receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.
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Ehrenkranz, Joel, and Michael A. Levine. "Bones and Joints: The Effects of Cannabinoids on the Skeleton." Journal of Clinical Endocrinology & Metabolism 104, no. 10 (August 8, 2019): 4683–94. http://dx.doi.org/10.1210/jc.2019-00665.
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Abstract Context The endocannabinoid system uses tissue-specific lipid ligands and G protein‒coupled transmembrane receptors to regulate neurologic, metabolic, and immune responses. Recent studies demonstrate that the endocannabinoid system influences bone metabolism. With the increasing use of endocannabinoid mimetics (e.g., tetrahydrocannabinol and cannabidiol), the involvement of endocannabinoids in bone growth and remodeling has become clinically relevant. Evidence Acquisition This literature review is based on a search of PubMed and Google Scholar databases as of June 2019 for all English-language publications relating to cannabinoids and bone. We evaluated retrieved articles for relevance, experimental design, data acquisition, statistical analysis, and conclusions. Evidence Synthesis Preclinical studies establish a role for endocannabinoids in bone metabolism. These studies yield complex and often contradictory results attributed to differences in the specific experimental model examined. Studies using human cells or subjects are limited. Conclusions In vitro and animal models document that endocannabinoids are involved in bone biology. The relevance of these observations to humans is not clear. The increasing long-term use of medical and recreational cannabis underscores the need to better understand the role of endocannabinoids in human bone metabolism. Moreover, it is important to evaluate the role of endocannabinoids as a therapeutic target to prevent and treat disorders associated with bone loss.
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Wang, Yanqing, and Brian D. Burrell. "Differences in chloride gradients allow for three distinct types of synaptic modulation by endocannabinoids." Journal of Neurophysiology 116, no. 2 (August 1, 2016): 619–28. http://dx.doi.org/10.1152/jn.00235.2016.
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Endocannabinoids can elicit persistent depression of excitatory and inhibitory synapses, reducing or enhancing (disinhibiting) neural circuit output, respectively. In this study, we examined whether differences in Cl−gradients can regulate which synapses undergo endocannabinoid-mediated synaptic depression vs. disinhibition using the well-characterized central nervous system (CNS) of the medicinal leech, Hirudo verbana. Exogenous application of endocannabinoids or capsaicin elicits potentiation of pressure (P) cell synapses and depression of both polymodal (Npoly) and mechanical (Nmech) nociceptive synapses. In P synapses, blocking Cl−export prevented endocannabinoid-mediated potentiation, consistent with a disinhibition process that has been indicated by previous experiments. In Nmechneurons, which are depolarized by GABA due to an elevated Cl−equilibrium potentials (ECl), endocannabinoid-mediated depression was prevented by blocking Cl−import, indicating that this decrease in synaptic signaling was due to depression of excitatory GABAergic input (disexcitation). Npolyneurons are also depolarized by GABA, but endocannabinoids elicit depression in these synapses directly and were only weakly affected by disruption of Cl−import. Consequently, the primary role of elevated EClmay be to protect Npolysynapses from disinhibition. All forms of endocannabinoid-mediated plasticity required activation of transient potential receptor vanilloid (TRPV) channels. Endocannabinoid/TRPV-dependent synaptic plasticity could also be elicited by distinct patterns of afferent stimulation with low-frequency stimulation (LFS) eliciting endocannabinoid-mediated depression of Npolysynapses and high-frequency stimulus (HFS) eliciting endocannabinoid-mediated potentiation of P synapses and depression of Nmechsynapses. These findings demonstrate a critical role of differences in Cl−gradients between neurons in determining the sign, potentiation vs. depression, of synaptic modulation under normal physiological conditions.
Dissertations / Theses on the topic "Endocannabinois"
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Serzysko, Malgorzata. "Endocannabinoids and excitotoxicity: lessons from hypoglossal motoneurons." Doctoral thesis, SISSA, 2015. http://hdl.handle.net/20.500.11767/3908.
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Brainstem hypoglossal motoneurons (HMs) exclusively innervate tongue muscles and are severely damaged in the neurodegenerative disease called amyotrophic lateral sclerosis (ALS). One mechanism leading to such cell death is proposed to be glutamate-mediated excitotoxic stress. HMs are particularly vulnerable to excitotoxicity due to their expression of calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors and scarcity of intracellular Ca2+ binding proteins like parvalbumin and calbindin. Indeed, blocking glutamate uptake in medullary slices can lead to pathological bursting and motoneuron damage.
The endocannabinoid system is widely distributed in the brain and is believed to be an important regulator of synaptic transmission. Several studies reported neuroprotection mediated by the endocannabinoid system in such pathological insults like brain ischemia, traumatic brain injury or excitotoxicity. Moreover, in ALS animal models, up-regulation of the endocannabinoid system has been detected, suggesting it can play a role during disease development. Thus, detailed information on how the endocannabinoid system can affect cells during pathological insults like excitotoxicity is a valuable asset for future investigations of novel therapy approaches for ALS.
The objective of this work was to investigate the effect of modulation of the endocannabinoid system during excitotoxic stress in hypoglossal motoneurons in vitro. Thin medullary slices (for electrophysiology and viability assay) or whole brainstem isolates (for Western Blot) from postnatal Wistar rats were used. Each slice/brainstem containing hypoglossal nuclei was transferred to a recording/incubation chamber and superfused with oxygenated Krebs solution. Excitotoxic stress was evoked by application of DL-TBOA (DL-threo-β-benzyloxyaspartic acid, 50 μM), a potent and selective inhibitor of excitatory amino acid transporters, with consequent build-up of extracellular glutamate.
It was observed that modulation of endocannabinoid CB1 receptor (CB1R) function affected TBOA-evoked bursting, an event previously correlated with TBOA toxicity. Co-application of the endocannabinoid anandamide (AEA, 10 μM), a CB1R agonist, with TBOA resulted in lowered probability of the occurrence of pathological bursting, whereas co-application of the CB1R antagonist AM251 (10 μM) disrupted TBOA-induced bursts, leading to their “fragmentation”. Furthermore, AEA significantly decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) isolated by co-application of bicuculline and strychnine (10 μM and 0.4 μM, respectively) and caused occurrence of biphasic activity in spontaneous inhibitory postsynaptic currents (sIPSCs; isolated by co-application of DNQX and APV at 10 μM and 50 μM, respectively) in some of the recorded cells. AM251 caused a decrease in the frequency of sIPSCs, but during application of bicuculline and strychnine it evoked activity which partly resembled bursting observed during TBOA application. Moreover, co-application of AEA with TBOA significantly decreased the number of damaged propidium iodide-positive cells with respect to counterstained Hoechst 33342-positive cells, which suggests a protective effect of this CB1R agonist against TBOA-induced toxicity. In addition, Western blot analysis showed a significant increase in CB1R protein levels after only 4 hours of TBOA incubation, indicating that the endocannabinoid system is activated during this excitotoxic insult. We suggest that a likely role of the endocannabinoid system in our brainstem preparation is to counteract the effects and consequences of elevated glutamate levels in the extracellular compartment.
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Mateu, Codina Gerard Àngel. "Factores genéticos en patología dual." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/667189.
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El término patología dual describe la coexistencia de una o más enfermedades mentales y trastornos por el uso de sustancias, la cual es muy común y, a menudo, se asocia con una mayor gravedad psiquiátrica y peores condiciones médicas y sociales. Últimamente ha adquirido relevancia la investigación relacionada con el papel del sistema endocannabinoide (eCB) en las bases neurobiológicas de diversas afecciones neuropsiquiátricas, tales como la ansiedad, los trastornos del estado de ánimo o la esquizofrenia, así como los trastornos relacionados con el uso de sustancias. El propósito de este estudio es investigar la asociación entre varios polimorfismos de los genes que codifican algunas proteínas del sistema endocannabinoide (receptor de cannabinoides 1 [CNR1] y amida hidrolasa de ácido graso [FAAH]) de acuerdo con (1) la presencia o ausencia de uso de sustancias trastornos en toda la muestra y (2) según la presencia o ausencia de patología dual en el grupo de sujetos diagnosticados con un trastorno por uso de sustancias. Es un estudio de casos y controles con un tamaño muestral de 675 sujetos, de los cuales 362 son controles (C; individuos sin diagnóstico psiquiátrico) y 313 casos (Cs; individuos con un trastorno por uso de sustancias sin ningún trastorno neuropsiquiátrico comórbido [ TCS] así como individuos con un trastorno de uso de sustancias con una enfermedad neuropsiquiátrica comórbida [PD]). Se compararon los grupos C y Cs y los grupos TCS y PD en base a datos demográficos, antecedentes familiares y personales de trastornos psiquiátricos y trastornos por uso de sustancias (mediante la versión española validada de la Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV)) y los rasgos de personalidad (evaluada con la versión española del Cloninger’s Temperament and Character Inventory (TCI-R). Se genotiparon 768 polimorfismos de nucleótido único (SNP) que se utilizaron como marcadores genéticos en una aproximación de estudio de gen candidato. Se realizaron análisis estadísticos simples de polimorfismos, genes y haplotipos así como un posterior análisis multivariante. Finalmente se relacionaron los resultados del análisis genético con las características sociodemográficas y clínicas de la muestra. Los sujetos Cs mostraron una mayor prevalencia de antecedentes familiares de enfermedades mentales y trastornos por uso de sustancias, así como una puntuación más baja en dependencia de la recompensa, autodirección, cooperación y autotrascendencia respecto a los sujetos C. Asimismo, los sujetos PD tenían mayor prevalencia de trastornos por consumo de alcohol y cocaína, menor prevalencia de trastornos por consumos de cannabis y mayor prevalencia de antecedentes familiares de enfermedades mentales y trastornos por uso de sustancias frente a los sujetos TCS. Además, los sujetos con TCS obtuvieron puntuaciones más altas en evitación del daño y autotrascendencia, aunque el resultado en autodirección fue significativamente más bajo en los sujetos con PD. Se halló una prevalencia significativa de las variantes AA/AC de SNP rs324420 y TT de SNP rs11576941 (ambos SNP que pertenecen al mismo haplotipo del gen FAAH) en el grupo Cs en el estudio de asociación de CS vs. C. La prevalencia fue también significativa en el caso de la variante TT del SNP rs11576941 que pertenece al gen FAAH en el grupo TCS en el estudio de asociación de TCS frente a C. Además, se detectó un subgrupo de sujetos del grupo de DP con puntuaciones significativamente más bajas en la dimensión de la personalidad evitación del daño que se caracterizan por ser homocigotos GG para el SNP rs806380 del gen CNR1. Esta variación alélica se ha asociado con una mayor sensibilidad para los estímulos positivos y podría representar un marcador endofenotípico para aquellos sujetos con mayor inestabilidad emocional y, por lo tanto, con mayor gravedad clínica potencial.The term dual pathology describes the coexistence of one or more mental illnesses and substance use disorders which is very common and is often associated with higher psychiatric severity, and worse medical conditions and social status. Likewise, there is now an important body of research on the important role that the endocannabinoid system (eCB) could play on the neurobiological bases of various neuropsychiatric conditions, such as anxiety, mood disorders or schizophrenia, in addition to several substance use disorders. The purpose of this study is to investigate the association between various polymorphisms of the genes encoding for some endocannabinoid system proteins (cannabinoid receptor 1 [CNR1] and fatty acid amide hydrolase [FAAH]) according to (1) the presence or absence of substance use disorders in the whole sample and (2) according to the presence or absence of dual pathology within the group of subjects diagnosed with a substance use disorder. This is a case-control study with a total sample size of 675 subjects, of whom 362 are controls (C; individuals without any psychiatric diagnosis) and 313 cases (Cs; individuals with a substance use disorder without any co-morbid neuropsychiatric condition [TCS] and those individuals with a substance use disorder with co-morbid neuropsychiatric condition [PD]). A comprehensive comparison including demographics, parental and personal background of psychiatric and substance use disorders (according to DSM-IV-R and performed by using the Spanish validated version of Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV)) and personality characteristics (evaluated using the Spanish version of the Cloninger’s Temperament and Character Inventory (TCI-R))was performed between both Cs and C groups and between TCS and PD groups. 768 single-nucleotide polymorphisms (SNPs) were genotyped wich were used as genetic markers in an approximation of candidate gene study. Simple statistical analysis of polymorphisms, genes and haplotypes and subsequent multivariate analysis were performed. We will relate the results of genetic analysis with sociodemographic and clinical characteristics. The phenotypical results of the comparison between both Cs and C groups showed that Cs subjects had greater prevalence of family background of mental illness and substance use disorders and a lower score on reward dependence, self-directness, cooperativeness and self-transcendence as regarding on personality traits. Likewise, TCS and PD groups contrast show that PD subjects had higher prevalence of alcohol and cocaine use disorders and lower prevalence of cannabis use disorder, as well as a higher prevalence of family background of mental illness and substance use disorders. In addition, TCS subjects had higher score on harm avoidance and self-transcendence but, interestingly, PD subjects score significantly lower on self-directness. We have found a significant prevalence of the AA/AC variants of SNP rs324420 and TT of SNP rs11576941 (both SNPs belonging to the same haplotype of the FAAH gene) in the Cs group in the association study of CS vs. C. The prevalence was significant in the case of the TT variant of the SNP rs11576941 belonging to the FAAH gene in the TCS group in the association study of TCS vs. C. Furthermore, a subgroup of subjects of the PD group with significantly lower scores in the personality dimension harm avoidance that are characterized by being homozygous GG for the SNP rs806380 of the CNR1 gene have been detected. This allelic variation has been associated with a greater sensitivity for positive stimuli and could represent an endophenotypic marker for those subjects with higher emotional instability and, therefore, with greater clinical potential severity.
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Strohm, Daniela. "Modulation der Insulinsignalgebung durch Prostaglandin E2 und Endocannabinoide." Phd thesis, Universität Potsdam, 2010. http://opus.kobv.de/ubp/volltexte/2011/4967/.
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Die adipositasbedingte Insulinresistenz geht mit einer unterschwelligen Entzündungsreaktion einher. Als Antwort auf dieses Entzündungsgeschehen wird PGE2 unter anderem von Kupffer Zellen der Leber freigesetzt und kann seine Wirkung über vier PGE2-Rezeptorsubtypen (EP1-EP4) vermitteln. In vorangegangenen Arbeiten konnte gezeigt werden, dass PGE2 in Rattenhepatozyten über den EP3 R ERK1/2-abhängig die intrazelluläre Weiterleitung des Insulinsignals hemmt. Über die Modulation der Insulinrezeptorsignalkette durch andere EP-Rezeptoren war bisher nichts bekannt. Daher sollte in stabil transfizierten Zelllinien, die jeweils nur einen der vier EP-Rezeptorsubtypen exprimierten, der Einfluss von PGE2 auf die Insulinrezeptorsignalkette untersucht werden. Es wurden HepG2-Zellen, die keinen funktionalen EP-Rezeptor aufwiesen, sowie HepG2-Zellen, die stabil den EP1-R (HepG2-EP1), den EP3β-R (HepG2 EP3β) oder den EP4-R (HepG2 EP4) exprimierten, sowie die humane fötale Hepatozytenzelllinie, Fh hTert, die den EP2- und den EP4-R exprimierte, für die Untersuchungen verwendet. Die Zellen wurden für 330 min mit PGE2 (10 µM) vorinkubiert, um die pathophysiologische Situation nachzustellen und anschließend mit Insulin (10 nM) für 15 min stimuliert. Die insulinabhängige Akt- und ERK1/2-Phosphorylierung wurde im Western-Blot bestimmt.
In allen Hepatomzelllinien die EP-R exprimierten, nicht aber in der Zelllinie, die keinen EP R exprimierte, hemmte PGE2 die insulinstimulierte Akt-Phosphorylierung. In allen drei stabil transfizierten Zelllinien, nicht jedoch in den Fh-hTert-Zellen, steigerte PGE2 die basale und insulinstimulierte Phosphorylierung der Serin/Threoninkinase ERK1/2. In den HepG2 EP1- und den HepG2-EP3β-Zellen steigerte PGE2 mutmaßlich über die ERK1/2-Aktivierung die Serinphosphorylierung des IRS, welche die Weiterleitung des Insulinsignals blockiert. Die Hemmung der Aktivierung von ERK1/2 hob in EP3 R-exprimierenden Zellen die Abschwächung der Insulinsignalübertragung teilweise auf. In diesen Zellen scheint die ERK1/2-Aktivierung die größte Bedeutung für die Hemmung der insulinstimulierten Akt-Phosphorylierung zu haben. Da durch die Hemmstoffe die PGE2-abhängige Modulation nicht vollständig aufgehoben wurde, scheinen darüber hinaus aber noch andere Mechanismen zur Modulation beizutragen. In den Fh hTert-Zellen wurde die Insulinrezeptorsignalkette offensichtlich über einen ERK1/2-unabhängigen, bisher nicht identifizierten Weg unterbrochen.
Eine gesteigerte PGE2-Bildung im Rahmen der Adipositas ist nicht auf die peripheren Gewebe beschränkt. Auch im Hypothalamus können bei Adipositas Zeichen einer Entzündung nachgewiesen werden, die mit einer gesteigerten PGE2-Bildung einhergehen. Daher wurde das EP R-Profil von primären hypothalamischen Neuronen und neuronalen Modellzelllinien charakterisiert, um zu prüfen, ob PGE2 in hypothalamischen Neuronen die Insulinsignalkette in ähnlicher Weise unterbricht wie in Hepatozyten. In allen neuronalen Zellen hemmte die Vorinkubation mit PGE2 die insulinstimulierte Akt-Phosphorylierung nicht. In der neuronalen hypothalamischen Zelllinie N 41 wirkte PGE2 eher synergistisch mit Insulin. In durch Retinsäure ausdifferenzierten SH SY5Y-Zellen waren die Ergebnisse allerdings widersprüchlich. Dies könnte darauf zurückzuführen sein, dass die Expression der EP Rezeptoren im Verlauf der Kultur stark schwankte und somit die EP R-Ausstattung der Zellen zwischen den Zellversuchen variierte. Auch in den primären hypothalamischen Neuronen variierte die EP R-Expression abhängig vom Differenzierungszustand und PGE2 beeinflusste die insulinstimulierte Akt-Phosphorylierung nicht. Obwohl in allen neuronalen Zellen die Akt-Phosphorylierung durch Insulin gesteigert wurde, konnte in keiner der Zellen eine insulinabhängige Regulation der Expression von Insulinzielgenen (POMC und AgRP) nachgewiesen werden. Das liegt wahrscheinlich an dem niedrigen Differenzierungsgrad der untersuchten Zellen.
Im Rahmen der Adipositas kommt es zu einer Überaktivierung des Endocannabinoidsystems. Endocannabinoidrezeptoren sind mit den EP Rezeptoren verwandt. Daher wurde geprüft, ob Endocannabinoide die Insulinsignalweiterleitung in ähnlicher Weise beeinflussen können wie PGE2. Die Vorinkubation der N 41-Zellen für 330 min mit einem Endocannabinoidrezeptoragonisten steigerte die insulinstimulierte Akt-Phosphorylierung, was auf einen insulinsensitiven Effekt von Endocannabinoiden hindeutet. Dies steht im Widerspruch zu der in der Literatur beschriebenen endocannabinoidabhängigen Insulinresistenz, die aber auf indirekte, durch Endocannabinoide ausgelöste Veränderungen zurückzuführen sein könnte.The obesity related insulin resistance is accompanied by a low grade inflammation. In response to inflammatory stimuli, PGE2 is released from Kupffer cells and signals through four G-Protein coupled PGE2-receptors (EP1-EP4). Previous work showed that PGE2 attenuated insulin signaling in rat hepatocytes through an EP3ß- and ERK1/2-dependent mechanism. Since EP-receptor expression on hepatocytes varies between species and physiological conditions, the effect of the individual EP receptor subtypes on insulin signaling was studied in hepatoma cell lines expressing individual EP receptor subtypes. HepG2 cells lacking functional EP-receptors, and derivatives stably expressing either EP1 receptor (HepG2-EP1), EP3ß receptor (HepG2-EP3ß) or EP4 receptor (HepG2-EP4) and Fh-hTert cells expressing EP2- and EP4-receptor were pre-incubated with PGE2 for 330 min to mimic the sub-acute inflammation. The cells were subsequently stimulated with insulin for 15 min. Akt and ERK1/2 activation was determined by Western Blotting with phospho-specific antibodies. PGE2 inhibited insulin stimulated Akt phosphorylation in all cell lines expressing EP receptors, except in HepG2 cells which are lacking functional EP receptors. PGE2 increased insulin stimulated phosphorylation of the serine/threonine kinase ERK1/2 in all EP R expressing HepG2 cell lines except in Fh-hTert cells. In HepG2-EP1 and HepG2 EP3ß cells PGE2 increased the serine phosphorylation of the insulin receptor substrate, presumably through an ERK1/2 activation. This IRS-serine phosphorylation leads to attenuation of insulin signal transduction. Inhibiting ERK1/2 activation with a specific inhibitor attenuated the PGE2-dependent inhibition of insulin signal transmission in HepG2 EP3ß cells to some extent. ERK1/2 activation in these cells seems to be of major importance for the observed attenuation of insulin stimulated Akt phosphorylation. Application of inhibitors in the other cell lines stably expressing EP receptors provided evidence that other mechanisms contributed to the attenuation of insulin signaling. Insulin signal transduction in Fh-hTert cells by PGE2 was apparently blocked by an ERK1/2-independent mechanism. Increased PGE2 production during obesity is not limited to the periphery. Signs of inflammation have been detected in the hypothalamus, which might be associated with an increased PGE2 production. Therefore, the EP receptor profile of primary neurons as well as neuronal cell models was characterised in order to investigate, whether PGE2 attenuates insulin signal transduction in neuronal cells similar to what was observed in hepatocytes. Pre-incubation with PGE2 did not attenuate insulin stimulated Akt phosphorylation in all neuronal cells. The EP receptor profile in SH SY5Y cells and in primary neurons varied depending on the differentiation status of the cells. Although Akt-kinase was phosphorylated in response to insulin stimulation in all neuronal cells studied, gene expression of insulin target genes (POMC, AgRP) was not modulated by insulin. This might be due to the low level of differentiation of the investigated cells. In the course of obesity, an over-activation of the endocannabinoid system is detected. Since endocannabinoid receptors are related to EP receptors, it was investigated whether endocannabinoids can interfere with insulin signaling in a similar way as PGE2. Pre-incubation of the neuronal cell line N 41 for 330 min with an endocannabinoid receptor agonist, increased insulin stimulated Akt phosphorylation. This implies an insulin sensitising effect of endocannabinoids. This is contradictory to the endocannabinoid-dependent insulin resistance described in the literature and might be caused by indirect endocannabinoid-triggered mechanisms.
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LISAI, SARA. "Nutritional factors influencing tissue omega-3 metabolism and endocannabinoids levels in experimental models and humans." Doctoral thesis, Università degli Studi di Cagliari, 2016. http://hdl.handle.net/11584/266644.
Full textAbstract:
The nutritional role of dietary fatty acids is quite controversial and often the object of mediatic campaigns either as panacea against all diseases or detrimental for human health. The most recent data are instead showing that it should be considered, in an optimal dietary regimen, the balance among all dietary fatty acids based on the current physiological needs, applying what it is currently known as personalised nutrition. It has been paid particular attention to the ratio between highly polyunsaturated fatty acids (HPUFAs) n-6, mainly arachidonic acid (ARA, 20:4n-6;) and n-3 HPUFAs, mainly eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) in tissues, since an inverse correlation between circulating n-3 HPUFAs and several chronic pathological states has been observed, possibly mediated by modulation of the endocannabinoid system (ECS). However, to assess this balance and controlling it by dietary means remains a great challenge for nutritionists. In addition, other nutritional factors may influence their tissue concentration. It is therefore compelling to individuate the mechanism(s) of action and what are the most efficient nutritional conditions to maximize n-3 HPUFAs health-related beneficial activities.
The aim of this thesis was to evaluate the effects of some nutritional factors, such as conjugated linoleic acid (CLA), naturally occurring in the diet or produced by the probiotic Bifidobacterium breve (B. breve), in influencing n-3 PUFA metabolism to optimize the n-3 HUFA score (a biomarker of n-3 status in tissues) and possible interactions with the ECS in rodents and humans.
We evaluated whether CLA, from different dietary sources, was able to enhance DHA biosynthesis, from its precursor alpha linolenic (ALA), in experimental models and humans. We found that different dietary ALA/CLA ratios affected n-3 PUFA and EC profile with a graded decrease of ALA and EPA and corresponding increase of DHA, while the EC arachidonoylethanolamine (AEA) decreased parallel to ratio ALA/CLA, whereas dietary ALA, in absence of CLA, was not able to increase significantly circulating DHA levels. We also evaluated whether supplementation with B. Breve as probiotic, along with ALA, in mice, as a nutritional factor that may increase dietary CLA, modulated n-3 fatty acid metabolism. We found that dietary probiotics increased DHA biosynthesis in liver and epididymal adipose tissue. Actually, we showed an increased of DHA biosynthesis in liver, but not an increase of CLA, while the ratio CD 16:2/CLA, a biomarker of peroxisomal beta oxidation, increased significantly but not associated to a higher PPAR α gene expression. The observed parameters suggested that these effects may be related to a pro-inflammatory event possibly triggered by the activation of toll like receptors by B. breve. In fact, in an ancillary experiment on rats challenged with LPS, we obtained similar results on fatty acid metabolism. In addition, dietary probiotics decreased AEA and its congener palmitoylethanolamine (PEA) levels in liver, while in adipose tissue we found a significant increased levels of AEA, PEA and the other AEA congener oleoylethanolamide (OEA).
Our studies strongly suggest that background diet may play an important role in modulating fatty acid metabolism and in particular in modulating n-3/n-6 fatty acid balance, thereby differently affecting the ECS. Therefore, the synergistic effects of different nutritional factors, as it occurs in daily life in humans are somewhat difficult to predict and may explain the contradictory results in the literature on the effects of dietary fatty acids, in particular when they are singularly considered without taking into account the whole dietary regimen. The discover that gut microbiota may directly interfere and modify fatty acid metabolism opens to novel nutritional strategies in shaping the optimal milieu for contrasting several metabolic disorders by modulating the ECS.
Future studies in humans will be focus on evaluating possible synergistic effects of CLA-enriched products with B. breve in maintaining and/or re-equilibrating energy and lipid metabolism, by modulating EC and congeners tissue profile, acting on energy metabolism and EPA and DHA related molecules, and also to assess if there is an optimal level of dietary EPA and DHA to allow a synergistic activity in different physio-pathological conditions.
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Patel, Annie. "Endocannabinoid turnover and function." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/12625/.
Full textAbstract:
The therapeutic benefits of cannabis have been known for centuries of years. Yet it has only been in the last 40 years that an understanding of the system by which its works in our bodies has begun to be defined. This has in turn led to the discovery and understanding of the endogenous cannabinoid (eCB) system, alongside its main synthesizing and hydrolysing enzymes as well as the endogenous ligands. The use of synthetic cannabinoid receptor (CBR) ligands for therapeutic use has provided problems regarding the natural endogenous regulatory tone of the eCBs, which in turn has resulted in unwanted side effects. Part of the reason of this is due to synthetic agonists producing the well documented psychotropic effects at CB t receptors. Alternative targets for the manipulation of the eCB system for therapeutic benefits have been explored. One remains to be the use of FAAH inhibitors, which in turn potentially increase levels of eCBs in the system, hence potentiating their effects at the CBRs, or at other receptor sites. Therefore we have developed two HTS assays for the identification of potential inhibitors of FAAH and MAGL. They prove to be robust, cheap and facile and provide a clear indication of inhibitable levels of FAAH and MAGL activity. The FAAH assay can be further used to establish concentration-response curves of initial `hit' compounds. Yet, the HTS MAGL assay requires further characterization for use in construction of concentration-response curves, as they are not assays specific for MAGL acitivity and include hydrolysis of the substrate 4-NPA by non-specific esterases. Z-factor scores were calculated for both assays, indicating excellent assays, which can potentially be applied to industrial lab robotics for screening of compound libraries.
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Kilaru, Aruna. "Endocannabinoid System in Plants?" Digital Commons @ East Tennessee State University, 2012. https://dc.etsu.edu/etsu-works/4781.
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Norris, Leonie. "Endocannabinoid modulation of nociceptive processing." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/28701/.
Full textAbstract:
The analgesic effects of cannabis-based medicines are widely described and elevation of the endocannabinoids (ECLs), by inhibition of endocannabinoid metabolism, also produces analgesia. Measurement of endocannabinoids (ECLs) and metabolites, in low weight biological tissue, provides an important tool for investigating the potential therapeutic effects of this receptor system. The main aims of this thesis were to develop an analytical method to measure ECLs, and cyclooxgenase-2 (COX-2) metabolites of anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and to apply the method to determine their role in nociceptive processing in models of acute and chronic inflammatory pain. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which allowed for the simultaneous measurement of AEA, oleoylethanolamide (OEA), palmitoylethanolamine (PEA) and 2-AG, as well as COX-2 metabolites of AEA and 2-AG was developed and validated. This method was demonstrated to be able to quantify ECLs and related compounds in rat hindpaw, brain, spinal cord and cell samples. The effects of TRPV1 activation on levels of intracellular calcium [Ca2+] and ECLs in sensory nerves were investigated. The TRPV1 agonist, capsaicin, dose dependently increased [Ca2+], which was blocked by the TRPV1 antagonist iodoresiniferatoxin (IRTX). Although synthesis of ECLs is activity and calcium dependent, there was no relationship between the TRPV1-mediated increases in [Ca2+], and levels of intracellular or extracellular ECLs. The mechanism of sensitization of primary afferent nociceptors by the proinflammatory cytokine tumor necrosis factor-α (TNFα), which is heavily implicated in inflammatory responses, was also studied. TNFα facilitated capsaicin-evoked calcium responses, an effect which was mediated by p38MAPK-induced phosphorylation. The ability of inhibition of fatty acid amide hydrolase (FAAH) to modulate inflammatory pain responses, and the sites at which ECLs were elevated, was studied in the carrageenan model of inflammatory pain. This model was considered ideal for the investigation of the role of alternative metabolism of ECLs by COX-2 as inflammatory pain is associated with an up-regulation of COX-2. The effects of acute and repeated administration of URB597 (0.3 mgkg-1), a selective inhibitor of FAAH metabolism of ECLs, on carrageenan-evoked changes in weight bearing and hindpaw oedema were determined. Behavioural effects were considered in parallel with the changes in levels of ECLs and COX-2 metabolites of AEA and 2-AG in the hindpaw and spinal cord. Acute administration of URB597 delayed the onset and attenuated carrageenan-induced hyperalgesia, an effect which was associated with increased levels of AEA, OEA and PEA in the spinal cord. By contrast, carrageenan-induced hyperalgesia was not altered by repeated administration of URB597 and levels of AEA in the spinal cord were not significantly increased by this treatment. There was no evidence for the metabolism of ECLs via COX-2 in the hindpaw, or spinal cord, of carrageenan-treated rats, under basal conditions or following inhibition of FAAH. The role of the endocannabinoid system in a model of osteoarthritis (OA) pain was also investigated. Intra-articluar injection of the chondrocyte inhibitor monosodium iodoacetate (MIA, 1 mg/50µl) produced histological changes reminiscent of joint damage in OA patients, and a time dependant decrease in paw withdrawal thresholds and weight bearing on the injured (ipsilateral) side. These behavioural pain responses were accompanied with an increase in ECLs in the spinal cord, suggestive of a role of ECLs in modulation of OA-induced pain.
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Chilufya, Jedaidah Y., Shivakumar P. Devaiah, Richard R. Sante, and Aruna Kilaru. "Endocannabinoid-Like Lipids in Plants." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/4747.
Full textAbstract:
Classically, endogenous fatty acid ethanolamides and their derivatives that bind to the cannabinoid receptors and trigger a signalling pathway are referred to as endocannabinoids. Although derivatives of arachidonic acid, including arachidonylethanolamine or anandamide, are the known endogenous ligands for cannabinoid receptors, other fatty acid ethanolamides or N-acylethanolamines (NAE) that vary in carbon chain length and saturation occur ubiquitously in eukaryotic organisms and play an important role in their physiology and development. The metabolic pathway for NAEs is highly conserved among eukaryotes and well characterised in mammalian systems. Although NAE pathway is only partly elucidated in plants, significant progress has been made in the past 20 years in understanding the implications of the metabolism of saturated and unsaturated endocannabinoid-like molecules in plant development and growth. The latest advancements in the field of plant endocannabinoid research are reviewed. Key Concepts Endocannabinoids are endogenous ligands of cannabinoid receptors in mammalian systems. Endocannabinoids belong to a class of small bioactive lipid molecules that are derivatives of fatty acids including their ethanolamides, referred to as N-acylethanolamines. N-Acylethanolamines are ubiquitous and their metabolic pathway is highly conserved among eukaryotes. In higher plants, only 12–18C N-acylethanolamines have been identified and their metabolic pathway is partly elucidated. The endocannabinoid-like lipids play an important role in seed germination, seedling development, flowering and cellular organisation. In plants, N-acylethanolamines also participate in mediating responses to biotic and abiotic stress.
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Lenz, Frederike. "The endocannabinoid system and autistic behavior in the Fmr1- KO mouse." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2018. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-231397.
Full textAbstract:
Background:
Background of this work was the investigation of the endocannabinoid system (ECS) in the Fmr1 knock- out (KO) mouse. The Fmr1- KO mouse is a mouse model for fragile X syndrome (FXS). FXS is the leading monogenic cause for autism spectrum disorders (ASD) in humans. The Fmr1- KO mouse displays autistic behavior such as an impaired social interaction, repetitive behavior, cognitive deficits, increased anxiety and aggressiveness. Alterations of the ECS have been suggested to play a key role in the etiopathology of a variety of neuropsychiatric disorders. Until today, little has been described about the involvement of the ECS in ASD.
Interrogation:
1. Evaluating the manifestation of typical cannabinoid- induced effects in the Fmr1- KO mouse
2. Investigating the influenceability of autistic symptoms with THC treatment in the Fmr1- KO mouse
3. Analyzing the signaling cascade of the stimulated and unstimulated ECS in different brain regions of the Fmr1- KO mouse
Material and Methods:
Experiments were carried out on adult (12±1 weeks old) male Fmr1- KO and Fmr1- wild- type (WT) mice from the C57BL/6J- (B6)- background. N= 15 mice received THC (10mg/kg bodyweight) and N= 16 received WIN55,212 (3mg/kg bodyweight). 30min after injection, the body temperature was measured and the distance animals moved in an open field during 15min was recorded (locomotion). Then, animals were placed with their forepaws onto a horizontally fixed bar and the time remaining in this position (catalepsy) was measured. Finally animals were placed on a preheated plate and the temperature at which a pain stimulus occurred was determined (testing analgesia). All 4 experiments are called tetrad experiment. Afterwards changes in body temperature, locomotion, catalepsy and analgesia of the animals was evaluated. To explore long-term effects of THC after the tetrad, N= 15 animals were tested in a social interaction test with a female contact mouse, 10 and 20 days after THC treatment. Therefore, the tested mouse and the contact mouse were placed together into a cage and the time mice spent in social interaction (nose, body and anogential sniffing, allogrooming and body contact) was manually quantified during 6min of recorded testing time. Another group of N= 19 received a premedication of rimonabant (Cannabinoid- receptor 1 (CB1) antagonist, 3mg/kg bodyweight) 30min prior to THC treatment. Rimonabant prevents THC from binding to CB1 and therefore allows the assessment of the involvement of CB1 in mediating social behavior. Furthermore the suggestibility of context-dependent fear conditioning with THC treatment has been tested on N= 13 mice. Animals were placed into a conditioning chamber that delivered 6 short electric shocks with a 30sec pause to their paws (conditioning phase). Immediately afterwards mice received THC or placebo. 24h later contextdependent fear was evaluated by quantification of the time mice spent freezing in the conditioning-chamber (fear) without receiving foot shocks. Intraneuronal signaling of the ECS was analyzed with N= 29 animals using western blots. Quantities of phosphorylated (“activated”) protein kinases (ERK, AKT and S6) from different brain homogenates (hippocampus, striatum, cortex and cerebellum) were therefore measured after THC or placebo injection (30 minutes prior to sacrificing).
Results:
Cannabinoids induced hypothermia, hypolocomotion, analgesia and catalepsy in WTmice. These effects were significantly less detectable in Fmr1- KO mice. Effects of both cannabinoids, THC and WIN55,212, were comparable with a slightly greater but not significant efficiency of THC. THC treated WT- mice exhibited further reduced social interaction 10 days after treatment, an effect that was partially prevented by premedication with rimonabant. THC increased social interaction in Fmr1- KO mice comparable to the level of untreated WT- mice. THC had no effect on behavior of WT- mice in context-dependent fear conditioning. Fmr1- KO mice showed significant less contextdependent fear conditioning compared to WT- mice. THC facilitated the recognition of an anxiety-correlated context in Fmr1- KO mice comparable to untreated WT- mice. In western blots significant changes in the THC- induced signaling cascade were detectable and depending on genotype, brain-region and analyzed protein-kinase. In the hippocampus there were no changes in untreated Fmr1- KO mice compared to WT- mice. THC had no effect on activation of protein-kinases in WT- and Fmr1- KO mice. In the striatum there were no changes in untreated Fmr1- KO mice compared to WTmice. THC significantly increased activity of ERK, AKT and S6 in WT-mice and not in Fmr1- KO mice. In the cortex of untreated Fmr1- KO mice AKT showed a significantly increased activity compared to WT- mice. THC significantly increased AKT activity in WT- mice without having an effect on KO- mice. In the cerebellum there were no changes in untreated Fmr1- KO mice compared to WT- mice. THC significantly increased ERK- activity in Fmr1- KO mice but had no effect on protein kinase activity in WT- mice.
Conclusion:
We observed physiological cannabinoid effects in WT- mice after treatment with THC and WIN55,212. These effects are significantly attenuated in Fmr1- KO mice. This may be interpreted as a desensitization of the ECS in the Fmr1- KO mouse. At the same time it was demonstrated that THC has the potential to improve context dependent memory consolidation and to increase social interaction in the Fmr1- KO mouse. In particular the influence of THC on impaired social interaction should be a target of further investigations to find possible therapeutic options for this typical symptom of Autism. Underlying molecular mechanisms remain unclear and the analysis of THC stimulated intraneuronal signaling gave no clear indication of possible molecular alterations in the Fmr1- KO mouse.
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Bonneville, Marika. "Endocannabinoid Modulation of Post-Ischemia Depression." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35056.
Full textAbstract:
Post-ischemia depression (PID) is a condition that affects approximately 30% of survivors from stroke or cardiac arrest and has an important impact on patients’ quality of life. Previous studies support important roles of the endocannabinoid (eCB) system in depression and brain ischemia. This study attempts to link all three variables together by investigating the role and mechanism of eCB signaling in the development of PID. A global ischemia + hypotension model was used to induce a PID phenotype in CD1 mice. Three ischemic time frames were tested, and even though all three could induce significant cell death in the CA1 region of the hippocampus, only the 15-minute time point led to an increased immobility time on the forced swimming test (FST). The main goal of this study was to investigate the effect of a cannabinoid type-I receptor (CB1R) antagonist/inverse agonist, AM281, on the development of two depressive symptoms: anhedonia, measured with the sucrose preference test (SPT), and behavioral despair, measured with the FST. AM281 administration was able to significantly reduce the symptoms of anhedonia and behavioural despair. Subsequently, the mechanism behind this antidepressant-like effect was investigated. Administration of bicuculine with AM281 did not significantly affect the antidepressant effect on the FST, therefore suggesting that AM281 does not act on GABAergic synapses. A similar protocol was adopted with NVP-AM077, where its administration combined with AM281 was able to block the effect of AM281, thus confirming the importance of glutamatergic synapses for the antidepressant effect of AM281. Furthermore, the administration of a TAT-GLUR2 peptide did not significantly affect the effect of AM281, implying that the astroglial cell-mediated LTD (long-term depression) at glutamatergic synapses is not involved in the antidepressant effects of AM281. Finally, a bilateral intra-BLA (basolateral nucleus of the amygdala) administration of AM281 was able to reduce the immobility time on the FST. In conclusion, these results highlight the important contribution of BLA glutamatergic synapses to the antidepressant-like effect conferred by AM281.
Books on the topic "Endocannabinois"
1
Pertwee, Roger G., ed. Endocannabinoids. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-20825-1.
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Abood, Mary E., Roger G. Sorensen, and Nephi Stella, eds. endoCANNABINOIDS. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-4669-9.
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Maccarrone, Mauro, ed. Endocannabinoid Signaling. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-2728-0.
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Maccarrone, Mauro, ed. Endocannabinoid Signaling. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-3539-0.
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Maccarrone, Mauro, ed. New Tools to Interrogate Endocannabinoid Signalling. Cambridge: Royal Society of Chemistry, 2020. http://dx.doi.org/10.1039/9781839160752.
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Kendall, Dave, and Stephen Alexander, eds. Behavioral Neurobiology of the Endocannabinoid System. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-88955-7.
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Behavioral neurobiology of the endocannabinoid system. Berlin: Springer-Verlag, 2009.
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Melis, Miriam, ed. Endocannabinoids and Lipid Mediators in Brain Functions. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-57371-7.
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J, Plutzky, Woods Stephen C, and sanofi aventis (Firm), eds. The endocannabinoid system and regulation of energy metabolism. [S.l: sanofi aventis, 2006.
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S, Onaivi Emmanuel, Sugiura Takayuki, and Di Marzo Vincenzo, eds. Endocannabinoids: The brain and body's marijuana and beyond. Boca Raton: Taylor & Francis, 2005.
Find full textBook chapters on the topic "Endocannabinois"
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Godlewski, Grzegorz, and George Kunos. "Overview of Nonclassical Cannabinoid Receptors." In endoCANNABINOIDS, 3–27. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-4669-9_1.
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Burston, James, and David Kendall. "Peroxisome Proliferator-Activated Receptors and Inflammation." In endoCANNABINOIDS, 221–33. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-4669-9_10.
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Mascia, Paola, Gianluigi Tanda, Sevil Yasar, Stephen J. Heishman, and Steven R. Goldberg. "Peroxisome Proliferator-Activated Nuclear Receptors and Drug Addiction." In endoCANNABINOIDS, 235–60. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-4669-9_11.
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Abood, Mary E., Roger G. Sorensen, and Nephi Stella. "Conclusions: Therapeutic Potential of Novel Cannabinoid Receptors." In endoCANNABINOIDS, 263–80. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-4669-9_12.
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Kotsikorou, Evangelia, and Patricia Reggio. "Overview of Non-CB1/CB2 Cannabinoid Receptors: Chemistry and Modeling." In endoCANNABINOIDS, 29–51. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-4669-9_2.
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Lu, Hui-Chen, Jane E. Lauckner, John W. Huffman, and Ken Mackie. "GPR55 in the CNS." In endoCANNABINOIDS, 55–69. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-4669-9_3.
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Whyte, Lauren S., and Ruth A. Ross. "The Role of GPR55 in Bone Biology." In endoCANNABINOIDS, 71–113. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-4669-9_4.
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Andradas, Clara, María M. Caffarel, Eduardo Pérez-Gómez, Manuel Guzmán, and Cristina Sánchez. "The Role of GPR55 in Cancer." In endoCANNABINOIDS, 115–33. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-4669-9_5.
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McHugh, Douglas, and Heather B. Bradshaw. "GPR18 and NAGly Signaling: New Members of the Endocannabinoid Family or Distant Cousins?" In endoCANNABINOIDS, 135–42. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-4669-9_6.
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Rimmerman, Neta, Ewa Kozela, Rivka Levy, Zvi Vogel, and Ana Juknat. "Cannabinoid Signaling Through Non-CB1R/Non-CB2R Targets in Microglia." In endoCANNABINOIDS, 143–71. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4614-4669-9_7.
Full textConference papers on the topic "Endocannabinois"
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"PV-003 - SISTEMA ENDOCANNABINOIDE EN DEPRESIÓN DUAL." In 24 CONGRESO DE LA SOCIEDAD ESPAÑOLA DE PATOLOGÍA DUAL. SEPD, 2022. http://dx.doi.org/10.17579/abstractbooksepd2022.pv003.
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Uno de los factores cruciales para el abordaje clínico de la comorbilidad entre depresión mayor (DM) y trastorno por consumo de alcohol (AUD) es determinar si la DM es primaria (DM-P) o bien inducida por consumo (DM-I), tanto por sus implicaciones pronósticas como para la estrategia terapéutica a seguir. Las investigaciones más recientes muestran que el riesgo de recaídas en el consumo de sustancias es aún mayor en pacientes diagnosticados de DM-I que de DMP, y se ha observado que algunos de los sujetos con DM-I, en seguimientos longitudinales son diagnosticados de DM-P. Así mismo, hay indicios de diferencias de respuesta a los fármacos antidepresivos según el tipo de depresión Como potenciales biomarcadores se ha postulado el sistema endocannabinoide (eCB), debido a la creciente evidencia científica que lo vincula a la fisiopatología de la DM. 1. Objetivos Realizar una revisión de la literatura científica para analizar el papel del sistema endocannabinoide en la depresión y el trastorno por consumo de alcohol. 2. Material y métodos Se realizará una revisión de la base de datos Pubmed. Se analizarán estudios en depresión y en trastorno por consumo de alcohol. Se presentarán los datos de manera narrativa y gráfica. Se analizará el potencial papel de endocannabinoides periféricos como biomarcadores para el diagnóstico diferencial entre depresión mayor primaria e inducida por alcohol. 3. Resultados y conclusiones. 14 artículos escogidos para revisión. Pendiente de análisis de resultados. A partir de los mismos se elaborará un plan de investigación empírico en el Hospital del Mar (Barcelona).
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Bilgic, Elif. "Endocannabinoid induced apoptotic cell death on endometriotic cells." In 15th International Congress of Histochemistry and Cytochemistry. Istanbul: LookUs Scientific, 2017. http://dx.doi.org/10.5505/2017ichc.op-12.
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Bouter, Y., M. Brzózka, C. Rohleder, R. Rygula, M. Leweke, J. Wiltfang, and U. Havemann-Reinecke. "Effects of social defeat on the endocannabinoid system." In Abstracts of the 30th Symposium of the AGNP. Georg Thieme Verlag KG, 2017. http://dx.doi.org/10.1055/s-0037-1606396.
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Gertsch, J. "Endocannabinoid signaling across species – evolution and perspectives for drug discovery." In 67th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA) in cooperation with the French Society of Pharmacognosy AFERP. © Georg Thieme Verlag KG, 2019. http://dx.doi.org/10.1055/s-0039-3399680.
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Abohalaka, Reshed, Turgut Emrah Bozkurt, Emirhan Nemutlu, Sevgen Celik Onder, and Inci Sahin-Erdemli. "The effect of endocannabinoid metabolism inhibition on airway inflammation in mice." In ERS International Congress 2019 abstracts. European Respiratory Society, 2019. http://dx.doi.org/10.1183/13993003.congress-2019.pa3878.
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Cruz, Leonardo Cardoso, Luis Gustavo Fraga Belotto, Sofia Dias Campos Machado, and Fabrício de Araújo Moreira. "Possible mechanisms of action of cannabidiol in the epilepsies: a review." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.045.
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Background: Cannabidiol (CBD) is a compound of Cannabis Sativa plant that has been studied since the 1970s for its effectiveness in the treatment of refractory epilepsies. With the discovery of the endocannabinoid system, most recent studies have been dedicated to elucidating its mechanisms of action. Objective: To review scientific articles in order to enlightening the antiepileptic cannabidiol’s mechanisms of action. Methods: Literature review on both PubMed and Google Scholar searching for the terms: “epilepsy”, “cannabidiol” and “mechanism of action”. Results: We found that cannabidiol has a lot of mechanisms of action which can explain its effectiveness, among which stand out: endocannabinoid system facilitation, by inhibition of recaption and hydrolysis of anandamide as well as by the facilitation of its synthesis and release. These processes must result in the indirect activation of CB1 and CB2 receptors. Furthermore, CBD promotes the activation of mTOR and PI3K proteins intracellular pathway, with subsequent reduction of glutamatergic release. Conclusions: The general hypothesis is that cannabidiol has antiepileptic effectiveness, even in cases of refractory epilepsies, precisely for showing several mechanisms of action. We emphasize, however, the necessity of more researches in this area for further enlightenment of theses possible mechanisms of action and the applicability in the treatment of epilepsies.
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Onnis, Valentina, Alessandro Deplano, and Monica Demurtas. "Discovery of novel endocannabinoid level modulators by modification of old analgesic drugs." In 4th International Electronic Conference on Medicinal Chemistry. Basel, Switzerland: MDPI, 2018. http://dx.doi.org/10.3390/ecmc-4-05590.
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Oscoz Irurozqui, Maitane, Maria Guardiola-Ripoll, Carmen Almodóvar-Payà, Salavador Sarró, Amalia Guerrero-Pedraza, Edith Pomarol-Clotet, and Mar Fatjó-Vilas. "Cannabis use and genes of endocannabinoid system: their role in psychotic symptoms and cognition in first-episode psychosis." In 22° Congreso de la Sociedad Española de Patología Dual (SEPD) 2020. SEPD, 2020. http://dx.doi.org/10.17579/sepd2020o031.
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Objectives. To evaluate the association of cannabis use, genes of the endocannabinoid system and their interaction on clinical symptoms and cognitive performance in patients with a first-episode of pyschosis. Background. The role of both cannabis use and individual genetic background has been shown in the risk for psychosis. However, the influence of cannabis and variability at endocannabinoid genes on the psychosis outcome still remains inconclusive. Materials and Methods. The sample comprised 43 Caucasian individuals with a first-episode of psychosis (mean age(sd)=25.80(6.39) years, 76.7% males, 51.2% cannabis users).There were no differences in age and sex between cannabis users and non-users. Genetic variability was assessed by genotyping one Single Nucleotide Polymorphism (SNP) in each gene (CNR1-rs1049353 and CNR2-rs2501431). Clinical (PANSS, GAF) and neuropsychological (WAIS, WMS, BADS) scales were administered. Results and conclusions. Genotypic frequencies did not differ between cannabis users and non-users. Cannabis use was associated with better manipulative abilities (IQ-M-WAIS, p=0.029) and better executive function (BADS, p=0.036). CNR1-T allele carriers presented higher disorganized and negative syndrome scores (p=0.001 and p=0.044, respectively). The interaction models evidenced a combined effect of CNR1 and cannabis use on the negative syndrome-PANSS (p=0.037). These results suggest the role of cannabis use and genetic background on cognitive and psychopathological outcomes in first-episode psychosis. However, evidence is still scant, and further investigation in larger samples is needed.
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Clendenen, S., R. Mcclain, and N. Clendenen. "B307 The effect of acetaminophen and total knee arthroplasty on endogenous plasma endocannabinoid levels." In ESRA Abstracts, 39th Annual ESRA Congress, 22–25 June 2022. BMJ Publishing Group Ltd, 2022. http://dx.doi.org/10.1136/rapm-2022-esra.381.
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Uer, O., C. Weisheit, L. Bindila, M. Velten, H. Treede, and G. D. Duerr. "Role of the Endocannabinoid System in Modulation of the Inflammatory Reaction in Aortic Valve Degeneration." In 50th Annual Meeting of the German Society for Thoracic and Cardiovascular Surgery (DGTHG). Georg Thieme Verlag KG, 2021. http://dx.doi.org/10.1055/s-0041-1725674.
Full textReports on the topic "Endocannabinois"
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Sallaberry, Chad, and Laurie Astern. The Endocannabinoid System, Our Universal Regulator. Journal of Young Investigators, June 2018. http://dx.doi.org/10.22186/jyi.34.5.48-55.
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Guzmán, Manuel. Endocannabinoides: un nuevo sistema de comunicación en el cerebro. Sociedad Española de Bioquímica y Biología Molecular (SEBBM), November 2010. http://dx.doi.org/10.18567/sebbmdiv_anc.2010.11.1.
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Gewirtz, David A. The Endocannabinoid System as a Target for Treatment of Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, August 2010. http://dx.doi.org/10.21236/ada535994.
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Molina, Patricia E. Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury. Fort Belvoir, VA: Defense Technical Information Center, November 2012. http://dx.doi.org/10.21236/ada576663.
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Molina, Patricia E. Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury. Fort Belvoir, VA: Defense Technical Information Center, November 2013. http://dx.doi.org/10.21236/ada599310.
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Lichtman, Aron. The Endocannabinoid System as a Target for Treatment of Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, August 2009. http://dx.doi.org/10.21236/ada550908.
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Lichtman, Aron. The Endocannabinoid System as a Target for Treatment of Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, August 2011. http://dx.doi.org/10.21236/ada558526.
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Kamaruzzaman, Mohd Amir, Muhammad Hibatullah Romli, Razif Abas, Sharmili Vidyadaran, Mohamad Taufik Hidayat Baharuldin, Muhammad Luqman Nasaruddin, Vishnnumukkala Thirupathirao, et al. Impact of Endocannabinoid Mediated Glial Cells on Cognitive Function in Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Animal Studies. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, August 2022. http://dx.doi.org/10.37766/inplasy2022.8.0094.
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Review question / Objective: This review aims to review systematically, and meta-analyse published pre-clinical research about the mechanism of endocannabinoid system modulation on glial cells and their effects on cognitive function in designated Alzheimer’s Disease (AD) in the animal model. Condition being studied: Its been acknowledged that the cure of Alzheimer's disease is still vague. Current medicine is working on symptoms only but never stop the disease progression due to neuronal loss. In recent years, researches have found that cannabinoid which is derived from cannabis sativa plant and its compounds exert neuroprotective effects in vitro and in vivo. In fact, cognitive improvement has been shown in some clinical studies. Therefore, the knowledge of cannabinoids and its interaction with living physiological environment like glial cells is crucial as immunomodulation to strategize the potential target of this substance. The original articles from related study relating endocannabinoid mediated glial cell were extracted to summarize and meta-analyze its impact and possible mechanism against cognitive decline in AD.
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Emery, Sean M., Aron H. Lichtman, and David A. Gewirtz. Involvement of the Endocannabinoid System in the Development and Treatment of Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, February 2013. http://dx.doi.org/10.21236/ada575843.
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Emery, Sean. Involvement of the Endocannabinoid System in the Development and Treatment of Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, February 2012. http://dx.doi.org/10.21236/ada560646.
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