title: Distribution patterns of cannabinoid CB1 receptors in the hippocampus of APPswe/PS1ΔE9 double transgenic mice.
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) APP(swe)/PS1(ΔE9) 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 APP(swe)/PS1(ΔE9) mice compared to non-transgenic littermates. Reduced CB1 expression in dtg APP(swe)/PS1(ΔE9) 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.
authors.affiliation: Department of Physiology and Biophysics, Howard University, Washington, DC 20059, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Kalifa
authors.forename: Eva K
authors.initials: EK
authors.lastname: Polston
authors.forename: Joanne S
authors.initials: JS
authors.lastname: Allard
authors.forename: Kebreten F
authors.initials: KF
authors.lastname: Manaye
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000172:deficiency / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D053764:Presenilin-1 / Q000172:deficiency / Q000235:genetics; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D043884:Receptor, Cannabinoid, CB1; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II