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
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...
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| Published in: | Frontiers in pharmacology Vol. 14; p. 1053680 |
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| Main Authors: | , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Switzerland
Frontiers Media S.A
03-03-2023
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | 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).
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 I
and
-values were used to assess heterogeneity.
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,
< 0.00001) and ability to discriminate novel objects (SMD = 1.40; 95% CI: 1.04 to 1.76,
< 0.00001) compared to the control group. Furthermore, a significant decrease in Aβ plaques (SMD = -0.91; 95% CI: -1.55 to -0.27,
= 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,
= 0.008) and Iba1 (SMD = -1.67; 95% CI: -2.56 to -0.79,
= 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,
= 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,
= 0.09), the result favored the endocannabinoid-treated group over the control group.
The revised data suggested that endocannabinoid stimulation promotes cognitive function
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.
[https://inplasy.com/inplasy-2022-8-0094/], identifier [Inplasy Protocol 3770]. |
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| Bibliography: | content type line 23 SourceType-Scholarly Journals-1 This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology Reviewed by: Haolong Liu, Health Science Centre, Peking University, China Edited by: Lee Wei Lim, The University of Hong Kong, Hong Kong SAR, China Diyang Lyu, Beijing Rehabilitation Hospital, Capital Medical University, China Hong Nie, Jinan University, China |
| ISSN: | 1663-9812 1663-9812 |
| DOI: | 10.3389/fphar.2023.1053680 |