CB2 cannabinoid receptor agonist ameliorates novel object recognition but not spatial memory in transgenic APP/PS1 mice

Li, Chao; Shi, Jingpu; Wang, Bo; Li, Jin; Jia, Huiqun

doi:10.1016/j.neulet.2019.134286

Cited by 49 publications

(41 citation statements)

References 40 publications

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“…Here, a long-term treatment with CB2R agonist decreased microgliosis and restored dendritic complexity in the cortex, but not in the hippocampus. This was reflected by improved performance in the cortex-dependent novel object recognition, whereas the performance in the hippocampus-dependent spatial memory Morris Water Maze (MWM) task was not altered [70]. These data suggest that the effect of CB2R activation on neuroinflammatory processes might also differ between brain regions.…”

Section: Alzheimer's Diseasementioning

confidence: 89%

CB2 Receptor in Microglia: The Guardian of Self-Control

Komorowska-Müller

Schmöle

2020

IJMS

106

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Microglia are key to maintaining the homeostasis of the brain. These immune cells of the brain can be our biggest ally in fighting infections, but can worsen pathology or hinder recovery when uncontrolled. Thus, understanding how microglia contribute to neuroinflammatory processes and how their activity can be controlled is of great importance. It is known that activation of endocannabinoid system, and especially the cannabinoid type 2 receptor (CB2R), decreases inflammation. Alongside its non-psychoactive effect, it makes the CB2R receptor a perfect target for treating diseases accompanied by neuroinflammation including neurodegenerative diseases. However, the exact mechanisms by which CB2R regulates microglial activity are not yet understood. Here, we review the current knowledge on the roles of microglial CB2R from in vitro and in vivo studies. We look into CB2R function under physiological and pathological conditions and focus on four different disease models representing chronic and acute inflammation. We highlight open questions and controversies and provide an update on the latest discoveries that were enabled by the development of novel technologies. Also, we discuss the recent findings on the role of microglia CB2R in cognition and its role in neuron–microglia communication.

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Section: Alzheimer's Diseasementioning

confidence: 89%

CB2 Receptor in Microglia: The Guardian of Self-Control

Komorowska-Müller

Schmöle

2020

IJMS

106

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“…However, only a few investigations have examined the role of eCB system modulation on microglial polarization. In a recent study using the APP/PS1 transgenic AD mouse model, administration of the CB2 agonist JWH015 for 8 weeks significantly decreased the expression of Iba1 + cells and proinflammatory cytokines and increased the expression of YM1/2 in the cortex (107). However, anti-inflammatory effects were not observed in the hippocampus.…”

Section: Microglial Polarization By Ecb In Neurodegenerative Disease mentioning

confidence: 93%

Endocannabinoid Modulation of Microglial Phenotypes in Neuropathology

2020

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Microglia, the resident immune cells of the central nervous system, mediate brain homeostasis by controlling neuronal proliferation/differentiation and synaptic activity. In response to external signals from neuropathological conditions, homeostatic (M0) microglia can adopt one of two activation states: the classical (M1) activation state, which secretes mediators of the proinflammatory response, and the alternative (M2) activation state, which presumably mediates the resolution of neuroinflammation and tissue repair/remodeling. Since chronic inflammatory activation of microglia is correlated with several neurodegenerative diseases, functional modulation of microglial phenotypes has been considered as a potential therapeutic strategy. The endocannabinoid (eCB) system, composed of cannabinoid receptors and ligands and their metabolic/biosynthetic enzymes, has been shown to activate anti-inflammatory signaling pathways that modulate immune cell functions. Growing evidence has demonstrated that endogenous, synthetic, and plant-derived eCB agonists possess therapeutic effects on several neuropathologies; however, the molecular mechanisms that mediate the anti-inflammatory effects have not yet been identified. Over the last decade, it has been revealed that the eCB system modulates microglial activation and population. In this review, we thoroughly examine recent studies on microglial phenotype modulation by eCB in neuroinflammatory and neurodegenerative disease conditions. We hypothesize that cannabinoid 2 receptor (CB2R) signaling shifts the balance of expression between neuroinflammatory (M1-type) genes, neuroprotective (M2-type) genes, and homeostatic (M0-type) genes toward the latter two gene expressions, by which microglia acquire therapeutic functionality.

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“…CB 2 receptors located on neurons and microglia in the spinal cord contribute to central sensitization in OA [ 98 ]. CB 2 receptors might play a role in the several neurological diseases, such as Alzheimer disease [ 99 , 100 ], depression [ 101 , 102 ], Parkinson disease [ 103 ] or memory formation [ 104 , 105 ]. However, since CB 2 in the other than peripheral location has been investigated recently, more studies are needed to clarify its role in various conditions.…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain: an updated review

Bryk

Starowicz

2021

Pharmacol. Rep

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Graphic abstract Over the last several decades, the percentage of patients suffering from different forms of arthritis has increased due to the ageing population and the increasing risk of civilization diseases, e.g. obesity, which contributes to arthritis development. Osteoarthritis and rheumatoid arthritis are estimated to affect 50–60% of people over 65 years old and cause serious health and economic problems. Currently, therapeutic strategies are limited and focus mainly on pain attenuation and maintaining joint functionality. First-line therapies are nonsteroidal anti-inflammatory drugs; in more advanced stages, stronger analgesics, such as opioids, are required, and in the most severe cases, joint arthroplasty is the only option to ensure joint mobility. Cannabinoids, both endocannabinoids and synthetic cannabinoid receptor (CB) agonists, are novel therapeutic options for the treatment of arthritis-associated pain. CB 1 receptors are mainly located in the nervous system; thus, CB 1 agonists induce many side effects, which limit their therapeutic efficacy. On the other hand, CB 2 receptors are mainly located in the periphery on immune cells, and CB 2 modulators exert analgesic and anti-inflammatory effects in vitro and in vivo. In the current review, novel research on the cannabinoid-mediated analgesic effect on arthritis is presented, with particular emphasis on the role of the CB 2 receptor in arthritis-related pain and the suppression of inflammation.

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CB2 cannabinoid receptor agonist ameliorates novel object recognition but not spatial memory in transgenic APP/PS1 mice

Cited by 49 publications

References 40 publications

CB2 Receptor in Microglia: The Guardian of Self-Control

CB2 Receptor in Microglia: The Guardian of Self-Control

Endocannabinoid Modulation of Microglial Phenotypes in Neuropathology

Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain: an updated review

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