Emerging roles of cannabinoid receptor CB2 receptor in the central nervous system: therapeutic target for CNS disorders.

RATIONALE: The endocannabinoid system (ECS) belongs to the G protein-coupled receptor family of cell membranes and is associated with neuropsychiatric conditions, and neurodegenerative diseases. Cannabinoid 2 receptors (CB2) are expressed in the central nervous system (CNS) on microglia and subgroups of neurons and are involved in various behavioural processes via immunological and neural regulation. OBJECTIVE: The objective of this paper is to summarize and explore the impact of CB2 receptors on neuronal modulation, their involvement in various neurological disorders, and their influence on mood, behavior, and cognitive function. RESULTS: The activation of CB2 appears to protect the brain and its functions from damage under neuroinflammatory actions, making it an attractive target in a variety of neurological conditions such as Parkinson's disease (PD), multiple sclerosis (MS), Alzheimer's disease (AD), and Huntington's disease (HD). During inflammation, there is an overexpression of CB2 receptors, and CB2 agonists show a strong anti-inflammatory effect. These results have sparked interest in the CB2 receptors as a potential target for neurodegenerative and neuroinflammatory disease treatment. CONCLUSION: In conclusion, CB2 receptors signalling shows promise for developing targeted interventions that could positively affect both immune and neuronal functions, ultimately influencing behavioral outcomes in both health and disease.

Cladribine induces apoptosis, neuroinflammation, mitochondrial oxidative stress, tau phosphorylation and Aß (1-42) pathway in the hippocampus: An in vivo approach.

Cladribine is a purine nucleoside found to enhance toxic amyloid protein and cause memory impairment. Patients following chemotherapy treatment commonly suffer from cognitive deficits more prevalent in the elderly than adults. A previous research study revealed that cladribine has a high affinity to the brain, increases the level of amyloid precursor protein, and results in learning deficits. The study was designed to validate an animal model of cladribine administration to rats through mitochondrial oxidative stress, inflammation, apoptosis, tau phosphorylation, and amyloid-ß (1-42) accumulation. In this study, all rats were orally given cladribine (0.5 and 1 mg/kg) for 28 days, resulting in impaired spatial memory confirmed by behavioural activity. On day 29, all rats were euthanized, and the hippocampal tissues were isolated and used for the estimation of neuroinflammatory markers, biochemicals parameters (glutathione, catalase, lipid peroxidation, and nitrite), amyloid-ß (1-42) level, neurotransmitters, and nuclear factor kappa B analysis. Cladribine administration significantly elevated cytokines release, dysbalanced neurotransmitter concentration, and promoted the Aß accumulation and hyperphosphorylation of tau protein. Our study outcome confirmed that cladribine produces cognitive impairment via activation of Nuclear factor kappa B, mitochondrial oxidative stress and dysbalanced of the endogenous antioxidant defence system.