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

Pharmacology

Kabul Warsito¹  Mohamad Taufik Hidayat Baharuldin²  Mohd Amir Kamaruzzaman³  Muhammad Luqman Nasaruddin⁴  Muhammad Amsyar Azwaruddin⁵  Mohamad Aris Mohd Moklas⁵  Nurul Huda Mohd Nor⁵  Razif Abas⁵  Sreenivasulu Sura⁶  Vishnumukkala Thirupathirao⁷  Muhammad Hibatullah Romli⁸  Sharmili Vidyadaran⁹  Mohammed Abdullah Alshawsh^1,10 

[1] Department of Agrotechnology, Faculty of Science and Technology, University of Pembangunan Panca Budi, Medan, Indonesia;Department of Anatomy, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia, Kuala Lumpur, Malaysia;Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia;Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia;Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia;Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia;Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia;Department of Preclinical Sciences, Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman, Kampar, Malaysia;Department of Human Biology, International Medical University, Kuala Lumpur, Malaysia;Department of Nursing and Rehabilitation, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia;Department of Pathology, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Kuala Lumpur, Malaysia;Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia;Department of Paediatrics, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Science, Monash University, Clayton, VIC, Australia;

关键词: Alzheimer’s disease;    cognition;    dementia;    endocannabinoid;    glial cell;    microglia;    astrocyte;    systematic review;   

DOI  :  10.3389/fphar.2023.1053680

 received in 2022-09-26, accepted in 2023-02-08,  发布年份 2023

来源: Frontiers

【 摘 要 】

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].

【 授权许可】

Unknown   
Copyright © 2023 Kamaruzzaman, Romli, Abas, Vidyadaran, Hidayat Baharuldin, Nasaruddin, Thirupathirao, Sura, Warsito, Mohd Nor, Azwaruddin, Alshawsh and Mohd Moklas.