Potentiation of microglial endocannabinoid signaling alleviates neuroinflammation in Alzheimer's disease

Rapaka, Deepthi; Bitra, Veera Raghavulu; Challa, Siva Reddy; Adiukwu, Paul Chukwuemeka

doi:10.1016/j.npep.2021.102196

Cited by 20 publications

(14 citation statements)

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“…Such contradictory results could be attributed to the variations in behavioral tasks performed, handling techniques, the timing of drug delivery or the type of medication therapy, or other experimental settings, as well as doses and CB compounds chosen (Kruk-Slomka et al, 2017). CB2R activation increases microglial cell migration and proliferation while reducing the release of inflammatory factors like TNF-α and free radicals, suggesting that anti-inflammatory effects occur secondary to activated CB2R in microglia (Rapaka et al, 2021). These effects also restore dendritic complexity in the cortex and improve memory for novel objects while not affecting plaque deposition or spatial memory (C. .…”

Section: Glial Cell-endocannabinoid Influences On Cognitive Changesmentioning

confidence: 99%

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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Section: Glial Cell-endocannabinoid Influences On Cognitive Changesmentioning

confidence: 99%

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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“…Endocannabinoids are lipophilic molecules that are able to bind and activate cannabinoid receptors. Cannabinoid receptors are G-protein-coupled receptors (GPCRs) found throughout the body, including the central and peripheral nervous systems [ 4 , 5 ]. Endocannabinoids, as a class of signaling lipids, contain amides and esters with a long chain of polyunsaturated fatty acids [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Endocannabinoids on Amyloid-Beta Aggregation and Toxicity

Khavandi

Rao

Beazely

2023

IJMS

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The regulation and metabolism of the endocannabinoid system has received extensive attention for their potential neuroprotective effect in neurodegenerative diseases such as Alzheimer’s disease (AD), which is characterized by amyloid β (Aβ) -induced cell toxicity, inflammation, and oxidative stress. Using in vitro techniques and two cell lines, the mouse hippocampus-derived HT22 cells and Chinese hamster ovary (CHO) cells expressing human cannabinoid receptor type 1 (CB1), we investigated the ability of endocannabinoids to inhibit Aβ aggregation and protect cells against Aβ toxicity. The present study provides evidence that endocannabinoids N-arachidonoyl ethanol amide (AEA), noladin and O-arachidonoyl ethanolamine (OAE) inhibit Aβ42 aggregation. They were able to provide protection against Aβ42 induced cytotoxicity via receptor-mediated and non-receptor-mediated mechanisms in CB1-CHO and HT22 cells, respectively. The aggregation kinetic experiments demonstrate the anti-Aβ aggregation activity of some endocannabinoids (AEA, noladin). These data demonstrate the potential role and application of endocannabinoids in AD pathology and treatment.

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“…The clinical manifestations include memory impairment, language, visuospatial, behavioural perceptions, and disturbances [2] . AD pathogenesis can be evident earlier before the symptoms become deceptive [3] .…”

Section: Introductionmentioning

confidence: 99%

Experimentally induced animal models for cognitive dysfunction and Alzheimer's disease

2022

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Potentiation of microglial endocannabinoid signaling alleviates neuroinflammation in Alzheimer's disease

Cited by 20 publications

References 146 publications

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

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

Differential Effects of Endocannabinoids on Amyloid-Beta Aggregation and Toxicity

Experimentally induced animal models for cognitive dysfunction and Alzheimer's disease

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