Kamaruzzaman, Mohd Amir and Romli, Muhammad Hibatullah and Abas, Razif and Vidyadaran, Sharmili and Baharuldin, Mohamad Taufik Hidayat and Nasaruddin, Muhammad Luqman and Thirupathirao, Vishnumukkala and Sura, Sreenivasulu and Warsito, Kabul and Nor, Nurul Huda Mohd and Azwaruddin, Muhammad Amsyar and Alshawsh, Mohammed Abdullah and Moklas, Mohamad Aris Mohd (2023) 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. Frontiers in Pharmacology, 14. ISSN 1663-9812, DOI https://doi.org/10.3389/fphar.2023.1053680.
Full text not available from this repository.Abstract
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 I-2 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 A beta 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-alpha, 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.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Higher Education, Malaysia, FRGS/1/2019/SKK08/UPM/02/16, Universiti Putra Malaysia |
| Uncontrolled Keywords: | Alzheimer's disease; Cognition; Dementia; Endocannabinoid; Glial cell; Microglia; Astrocyte; Systematic review |
| Subjects: | R Medicine > RC Internal medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 27 Nov 2023 01:09 |
| Last Modified: | 27 Nov 2023 01:09 |
| URI: | http://eprints.um.edu.my/id/eprint/38464 |
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