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

• Published in: Brain research 2011-02, Vol.1376, p.94-100
• Main Authors: Kalifa, Sara, Polston, Eva K, Allard, Joanne S, Manaye, Kebreten F
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - immunology; Alzheimer Disease - metabolism; Amyloid beta-Protein Precursor - deficiency; Amyloid beta-Protein Precursor - genetics; Animals; Astrocytes - metabolism; Biological and medical sciences; Blotting, Western; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Hippocampus - immunology; Hippocampus - metabolism; Immunohistochemistry; Male; Medical sciences; Mice; Mice, Transgenic; Neurology; Neurons - metabolism; Neuropharmacology; Nitric Oxide Synthase Type II - biosynthesis; Pharmacology. Drug treatments; Presenilin-1 - deficiency; Presenilin-1 - genetics; Psychodysleptics: hallucinogen; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptor, Cannabinoid, CB1 - biosynthesis; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2010.12.061

Abstract 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.