Cannabinoid CB1 receptors in the hippocampus of the APP/PS1 double transgenic murine model of Alzheimer's disease neuropathology.

摘要

Studies performed to date clearly indicate that cannabinoids have neuroprotective effect and these effects occur primarily through cannabinoid CB1 receptors. The study in hand investigated differences in the CB1 receptor density between the CA1 and CA2/3 regions of the hippocampus of male double transgenic (dtg) APP/PS1 mice model of Alzheimer's disease and age matched control littermate. CB1 protein was highly expressed in the hippocampus and the greatest density was found in CA2/3 region. Comparison of the CB1 protein expression of the APP/PS1 mice with age matched non-transgenic control mice showed a significant decline in CB1 receptor protein in the dtg model. However, in the middle aged APP/PS1 mice, the degree of CB1-immunoreactive cell loss due to genotype was significantly lower than that of total cell loss in the hippocampus. In addition, pronounced cell loss and astrocyte proliferation were observed in CA1 region of the hippocampus where lower CB1 receptor levels were observed. Hence, an inverse relationship of CB1 receptor expression with cell loss and astrogliosis is demonstrated, suggesting the possibility that endocannabinoids as anti-inflammatory agents in Alzheimer's disease neuropathology. The study also looks at age-related changes in CB1 protein expression. Comparison between young (3-6 months) and middle aged (10-13 month) dtg mice demonstrated a slight decrease in CB1 protein expression in the middle aged dtg mice, though a significant increase in plaque load and astrogliosis with aging in the dtg model was determined in this study. The present study demonstrates region-specific changes in levels of CB1-immunoreactive neurons in the hippocampus in relation to genotype and aging and further suggests that cannabinoid CB1 receptors may inhibit the inflammatory process of Alzheimer's disease.;The study would be incomplete without characterizing the AD model. This entails determining the extent of neuron loss, levels of cytokines (TNF-&agr; and iNOS), astrogliosis and plaque formation between the APP/PS1 double transgenic model of AD and the control group. To this end, Western blotting, and design-based stereology were utilized. The chief finding among many others of the exercise is that there is a significant neurodegeneration, elevated levels of cytokines and astrocytes, as well as increased plaque formation in the hippocampus of the double transgenic mice.