Murat Çakır1, Suat Tekin2, Züleyha Doğanyiğit3, Yavuz Erden4, Merve Soytürk2, Yılmaz Çiğremiş5, Süleyman Sandal2. 1. Faculty of Medicine, Department of Physiology, University of Bozok, Yozgat 66200, Turkey. Electronic address: murat.cakir@bozok.edu.tr. 2. Faculty of Medicine, Department of Physiology, University of Inonu, Malatya 44280, Turkey. 3. Faculty of Medicine, Department of Histology and Embryology, University of Bozok, Yozgat 66200, Turkey. 4. Department of Molecular Biology and Genetics, Faculty of Science, Bartın University, Bartın 74100, Turkey. 5. Department of Medical Biology and Genetics, Faculty of Medicine, Inonu University, Malatya 44280, Turkey.
Abstract
AIM: 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. MATERIALS AND METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
AIM: 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. MATERIALS AND METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.