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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
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 modulatio...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10028478/ https://www.ncbi.nlm.nih.gov/pubmed/36959856 http://dx.doi.org/10.3389/fphar.2023.1053680 |
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author | Kamaruzzaman, Mohd Amir Romli, Muhammad Hibatullah Abas, Razif Vidyadaran, Sharmili Hidayat Baharuldin, Mohamad Taufik Nasaruddin, Muhammad Luqman Thirupathirao, Vishnumukkala Sura, Sreenivasulu Warsito, Kabul Mohd Nor, Nurul Huda Azwaruddin, Muhammad Amsyar Alshawsh, Mohammed Abdullah Mohd Moklas, Mohamad Aris |
author_facet | Kamaruzzaman, Mohd Amir Romli, Muhammad Hibatullah Abas, Razif Vidyadaran, Sharmili Hidayat Baharuldin, Mohamad Taufik Nasaruddin, Muhammad Luqman Thirupathirao, Vishnumukkala Sura, Sreenivasulu Warsito, Kabul Mohd Nor, Nurul Huda Azwaruddin, Muhammad Amsyar Alshawsh, Mohammed Abdullah Mohd Moklas, Mohamad Aris |
author_sort | Kamaruzzaman, Mohd Amir |
collection | PubMed |
description | 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 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]. |
format | Online Article Text |
id | pubmed-10028478 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100284782023-03-22 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 Kamaruzzaman, Mohd Amir Romli, Muhammad Hibatullah Abas, Razif Vidyadaran, Sharmili Hidayat Baharuldin, Mohamad Taufik Nasaruddin, Muhammad Luqman Thirupathirao, Vishnumukkala Sura, Sreenivasulu Warsito, Kabul Mohd Nor, Nurul Huda Azwaruddin, Muhammad Amsyar Alshawsh, Mohammed Abdullah Mohd Moklas, Mohamad Aris Front Pharmacol Pharmacology 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 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]. Frontiers Media S.A. 2023-03-03 /pmc/articles/PMC10028478/ /pubmed/36959856 http://dx.doi.org/10.3389/fphar.2023.1053680 Text en Copyright © 2023 Kamaruzzaman, Romli, Abas, Vidyadaran, Hidayat Baharuldin, Nasaruddin, Thirupathirao, Sura, Warsito, Mohd Nor, Azwaruddin, Alshawsh and Mohd Moklas. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Kamaruzzaman, Mohd Amir Romli, Muhammad Hibatullah Abas, Razif Vidyadaran, Sharmili Hidayat Baharuldin, Mohamad Taufik Nasaruddin, Muhammad Luqman Thirupathirao, Vishnumukkala Sura, Sreenivasulu Warsito, Kabul Mohd Nor, Nurul Huda Azwaruddin, Muhammad Amsyar Alshawsh, Mohammed Abdullah Mohd Moklas, Mohamad Aris 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10028478/ https://www.ncbi.nlm.nih.gov/pubmed/36959856 http://dx.doi.org/10.3389/fphar.2023.1053680 |
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