Endocannabinoid signaling in brain diseases: Emerging relevance of glial cells

Bernal‐Chico, Ana; Tepavčević, Vanja; Manterola, Andrea; Utrilla, Carmen; Matute, Carlos; Mato, Susana

doi:10.1002/glia.24172

Cited by 22 publications

(17 citation statements)

References 262 publications

(423 reference statements)

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“…Given the choice of assessing vGlut1 and vGAT boutons, we were unable to confirm the cell types of CB1R-IR + puncta that did not demonstrate co-labeling, and it is likely these non-vGlut1 and non-vGAT puncta represent a variety of cell types such as vGlut2-expressing glutamatergic neurons 54 . Of note, recent studies have also demonstrated the presence of CB1R in non-GABAergic and non-glutamatergic cell types (e.g., astrocytes, dopaminergic neurons) 55 , as well as in a variety of different subcellular organelles (e.g., lysosomes, endosomes, mitochondria) 56 , and future studies should expand into the investigation of subcellular CB1R localization in postmortem human brain samples.…”

Section: Discussionmentioning

confidence: 98%

Cell type specific cannabinoid CB1 receptor distribution across the human and non-human primate cortex

Chou

Ranganath

Fish

et al. 2022

Sci Rep

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Alterations in cannabinoid CB1 receptor (CB1R) are implicated in various psychiatric disorders. CB1R participates in both depolarization induced suppression of inhibition (DSI) and depolarization induced suppression of excitation (DSE), suggesting its involvement in regulating excitatory and inhibitory (E/I) balance. Prior studies examining neuronal cell type specific CB1R distribution have been conducted near exclusively within rodents. Identification of these distribution patterns within the human and non-human primate cortex is essential to increase our insight into its function. Using co-labeling immunohistochemistry and fluorescent microscopy, we examined CB1R protein levels within excitatory and inhibitory boutons of male human and non-human primate prefrontal cortex and auditory cortices, regions involved in the behavioral effects of exogenous cannabinoid exposures. We found that CB1R was present in both bouton populations within all brain regions examined in both species. Significantly higher CB1R levels were found within inhibitory than within excitatory boutons across all regions in both species, although the cell type by brain region interactions differed between the two species. Our results support the importance of conducting more in-depth CB1R examinations to understand how cell type and brain region dependent differences contribute to regional E/I balance regulation, and how aberrations in CB1R distribution may contribute to pathology.

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Section: Discussionmentioning

confidence: 98%

Cell type specific cannabinoid CB1 receptor distribution across the human and non-human primate cortex

Chou

Ranganath

Fish

et al. 2022

Sci Rep

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“…In addition, De Chiara et al uncovered a novel mechanism by which BDNF influences the function of striatal CB1R (De Chiara et al, 2010). In another study, Abd El-Rahman and Fayed (2022) reported improved cognition in D-galactoseinjected ovariectomized rats via CB2R activation modulating the CREB/BDNF signaling pathway. This promoted CREB phosphorylation for the expression of various pro-survival genes such as BDNF and Bcl-2 which later enhanced the expression of both antioxidant enzymes and the antiapoptotic protein and reduced delayed neuronal death.…”

Section: Glial Cell-endocannabinoid-mediated Synaptic Plasticitymentioning

confidence: 96%

Regulatory role of the endocannabinoid system on glial cells toward cognitive function in Alzheimer’s disease: A systematic review and meta-analysis of animal studies

et al. 2023

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Objective: Over the last decade, researchers have sought to develop novel medications against dementia. One potential agent under investigation is cannabinoids. This review systematically appraised and meta-analyzed published pre-clinical research on the mechanism of endocannabinoid system modulation in glial cells and their effects on cognitive function in animal models of Alzheimer’s disease (AD).Methods: A systematic review complying with PRISMA guidelines was conducted. Six databases were searched: EBSCOHost, Scopus, PubMed, CINAHL, Cochrane, and Web of Science, using the keywords AD, cannabinoid, glial cells, and cognition. The methodological quality of each selected pre-clinical study was evaluated using the SYRCLE risk of bias tool. A random-effects model was applied to analyze the data and calculate the effect size, while I2 and p-values were used to assess heterogeneity.Results: The analysis included 26 original articles describing (1050 rodents) with AD-like symptoms. Rodents treated with cannabinoid agonists showed significant reductions in escape latency (standard mean difference [SMD] = −1.26; 95% confidence interval [CI]: −1.77 to −0.76, p < 0.00001) and ability to discriminate novel objects (SMD = 1.40; 95% CI: 1.04 to 1.76, p < 0.00001) compared to the control group. Furthermore, a significant decrease in Aβ plaques (SMD = −0.91; 95% CI: −1.55 to −0.27, p = 0.006) was observed in the endocannabinoid-treated group compared to the control group. Trends were observed toward neuroprotection, as represented by decreased levels of glial cell markers including glial fibrillary acid protein (SMD = −1.47; 95% CI: −2.56 to −0.38, p = 0.008) and Iba1 (SMD = −1.67; 95% CI: −2.56 to −0.79, p = 0.0002). Studies on the wild-type mice demonstrated significantly decreased levels of pro-inflammatory markers TNF-α, IL-1, and IL-6 (SMD = −2.28; 95% CI: −3.15 to −1.41, p = 0.00001). Despite the non-significant decrease in pro-inflammatory marker levels in transgenic mice (SMD = −0.47; 95% CI: −1.03 to 0.08, p = 0.09), the result favored the endocannabinoid-treated group over the control group.Conclusion: The revised data suggested that endocannabinoid stimulation promotes cognitive function via modulation of glial cells by decreasing pro-inflammatory markers in AD-like rodent models. Thus, cannabinoid agents may be required to modulate the downstream chain of effect to enhance cognitive stability against concurrent neuroinflammation in AD. Population-based studies and well-designed clinical trials are required to characterize the acceptability and real-world effectiveness of cannabinoid agents.Systematic Review Registration: [https://inplasy.com/inplasy-2022-8-0094/], identifier [Inplasy Protocol 3770].

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“…The first mechanism occurs in the peripheral immune system, where CB2Rs mediate analgesia by modifying the cytokine profile and preventing adverse effects on the CNS. Secondly, CB2Rs present in glial cells and neurons contribute to pain relief [ 173 , 174 ]. Additionally, studies have shown that selective CB2 agonists promote antinociception [ 175 , 176 ].…”

Section: Endocannabinoid System Emerging As a Pharmacotherapy Target ...mentioning

confidence: 99%

Endocannabinoid System: Chemical Characteristics and Biological Activity

Rezende

Alencar²,

de³

et al. 2023

Pharmaceuticals

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The endocannabinoid system (eCB) has been studied to identify the molecular structures present in Cannabis sativa. eCB consists of cannabinoid receptors, endogenous ligands, and the associated enzymatic apparatus responsible for maintaining energy homeostasis and cognitive processes. Several physiological effects of cannabinoids are exerted through interactions with various receptors, such as CB1 and CB2 receptors, vanilloid receptors, and the recently discovered G-protein-coupled receptors (GPR55, GPR3, GPR6, GPR12, and GPR19). Anandamide (AEA) and 2-arachidoylglycerol (2-AG), two small lipids derived from arachidonic acid, showed high-affinity binding to both CB1 and CB2 receptors. eCB plays a critical role in chronic pain and mood disorders and has been extensively studied because of its wide therapeutic potential and because it is a promising target for the development of new drugs. Phytocannabinoids and synthetic cannabinoids have shown varied affinities for eCB and are relevant to the treatment of several neurological diseases. This review provides a description of eCB components and discusses how phytocannabinoids and other exogenous compounds may regulate the eCB balance. Furthermore, we show the hypo- or hyperfunctionality of eCB in the body and how eCB is related to chronic pain and mood disorders, even with integrative and complementary health practices (ICHP) harmonizing the eCB.

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Endocannabinoid signaling in brain diseases: Emerging relevance of glial cells

Cited by 22 publications

References 262 publications

Cell type specific cannabinoid CB1 receptor distribution across the human and non-human primate cortex

Cell type specific cannabinoid CB1 receptor distribution across the human and non-human primate cortex

Regulatory role of the endocannabinoid system on glial cells toward cognitive function in Alzheimer’s disease: A systematic review and meta-analysis of animal studies

Endocannabinoid System: Chemical Characteristics and Biological Activity

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