jwh-133 and Memory-Disorders

Cannabinoid system has various physiological roles such as neurogenesis, synaptic plasticity and emotional state regulation in the body. The presence of cannabinoid type 2 receptor (CB2), a member of the cannabinoid system, was detected in different regions of the brain. CB2 receptor plays a role in neuroinflammatory and neurodegenerative processes. We aimed to determine the possible effect of CB2 agonist JWH-133 in Okadaic acid (OKA)-induced neurodegeneration model mimicking Alzheimer's Disease (AD) through tau pathology.. In this study, 40 Sprague Dawley male rats were divided into 4 groups (Control, Sham, OKA, OKA + JWH-133). Bilateral intracerebroventricular (icv) injection of 200 ng OKA was performed in the OKA group. In the OKA + JWH-133 group, injection of JWH-133 (0.2 mg/kg) was performed intraperitoneally for 13 days different from the group of OKA. Morris water maze test was used to evaluate the spatial memory. Levels of caspase-3, phosphorylated tau (ser396), amyloid beta (Aβ), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in brain cortex; and the hippocampus regions were examined by immunohistochemical methods.. In the OKA group, caspase-3, phosphorylated tau (ser396), Aβ, IL-1β levels were higher in the cortex and hippocampus than in the other groups. The implementation of the JWH-133 reversed the increments in these parameters, and also prevented spatial memory impairment.. In this study, we found that the administration of the CB2 receptor agonist JWH-133 in this study reduced neurodegeneration, neuroinflammation, and spatial memory impairment in the OKA-induced Alzheimer's Disease model.

Topics: Animals; Brain; Cannabinoids; Male; Memory Disorders; Neuroprotective Agents; Okadaic Acid; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB2; Spatial Memory; tau Proteins

Topics: Adenylate Kinase; Aging; Alzheimer Disease; Aminoimidazole Carboxamide; Animals; Cannabinoids; Enzyme Activation; Gene Deletion; Glycogen Synthase Kinase 3 beta; Hippocampus; Memory; Memory Disorders; Mice, Inbred C57BL; Mice, Transgenic; Mitochondria; Phosphorylation; Receptor, Cannabinoid, CB2; Resveratrol; Ribonucleotides; Signal Transduction; tau Proteins

In this study, the role of CB₂r on aversive memory consolidation was further evaluated. Mice lacking CB₂r (CB2KO) and their corresponding littermates (WT) were exposed to the step-down inhibitory avoidance test (SDIA). MAP2, NF200 and synaptophysin (SYN)-immunoreactive fibers were studied in the hippocampus (HIP) of both genotypes. The number of synapses, postsynaptic density thickness and the relation between the synaptic length across the synaptic cleft and the distance between the synaptic ends were evaluated in the HIP (dentate gyrus (DG) and CA1 fields) by electron microscopy. Brain-derived neurotrophic factor (BDNF), glucocorticoid receptor (NR3C1) gene expressions and mTOR/p70S6K signaling cascade were evaluated in the HIP and prefrontal cortex (PFC). Finally, the effects of acute administration of CB₂r-agonist JWH133 or CB2r-antagonist AM630 on memory consolidation were evaluated in WT mice by using the SDIA. The lack of CB₂r impaired aversive memory consolidation, reduced MAP2, NF200 and SYN-immunoreactive fibers and also reduced the number of synapses in DG of CB2KO mice. BDNF and NR3C1 gene expression were reduced in the HIP of CB2KO mice. An increase of p-p70S6K (T389 and S424) and p-AKT protein expression was observed in the HIP and PFC of CB2KO mice. Interestingly, administration of AM630 impaired aversive memory consolidation, whereas JWH133 enhanced it. Further functional and molecular assessments would have been helpful to further support our conclusions. These results revealed that CB₂r are involved in memory consolidation, suggesting that this receptor could be a promising target for developing novel treatments for different cognitive impairment-related disorders.

Topics: Animals; Avoidance Learning; Brain-Derived Neurotrophic Factor; Cannabinoid Receptor Agonists; Cannabinoid Receptor Antagonists; Cannabinoids; Gene Expression; Hippocampus; Indoles; Memory; Memory Disorders; Mice; Mice, Knockout; Microtubule-Associated Proteins; Neurofilament Proteins; Neuronal Plasticity; Prefrontal Cortex; Receptor, Cannabinoid, CB2; Receptors, Glucocorticoid; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Synapses; Synaptophysin; TOR Serine-Threonine Kinases