Distribution patterns of cannabinoid CB1 receptors in the hippocampus of APPswe/PS1ΔE9 double transgenic mice

Cannabinoids have neuroprotective effects that are exerted primarily through cannabinoid CB1 receptors in the brain. This study characterized CB1 receptor distribution in the double transgenic (dtg) APPswe/PS1ΔE9 mouse model for Alzheimer's disease. Immunohistochemical labeling of CB1 protein in non-transgenic mice revealed that CB1 was highly expressed in the hippocampus, with the greatest density of CB1 protein observed in the combined hippocampal subregions CA2 and CA3 (CA2/3). CB1 immunoreactivity in the CA1 and CA2/3 hippocampal regions was significantly decreased in the dtg APPswe/PS1ΔE9 mice compared to non-transgenic littermates. Reduced CB1 expression in dtg APPswe/PS1ΔE9 mice was associated with astroglial proliferation and elevated expression of the cytokines inducible nitric oxide synthase and tumor necrosis factor alpha. This finding suggests an anti-inflammatory effect of cannabinoids that is mediated by CB1 receptor, particularly in the CA2/3 region of the hippocampus. Furthermore, the study suggests a decreased CB1 receptor expression may result in diminished anti-inflammatory processes, exacerbating the neuropathology associated with Alzheimer's disease.

Research HighlightsThe significant findings were:
► Reduction of CB1-IR neurons in CA1 hippocampal region of dtg APPswe/PS1ΔE9 mice.
► Increased astrocytes in CA1 compared to CA2/3 region in dtg APPswe/PS1ΔE9 mice.
► Increased levels of iNOS and TNFα in the hippocampus of dtg APPswe/PS1ΔE9 mice.