title: Experimentally induced diabetes worsens neuropathology, but not learning and memory, in middle aged 3xTg mice.
abstract: Alzheimer's disease (AD) is the primary cause of dementia in the elderly. The cause of the disease is still unknown, but amyloid plaques and neurofibrillary tangles in the brain are thought to play a role. However, transgenic mouse models expressing these neuropathological features do not show severe or consistent cognitive impairments. There is accumulating evidence that diabetes increases the risk for developing AD. We tested the hypothesis that experimentally induced diabetes would exacerbate cognitive symptoms in a mouse model of AD. Diabetes was induced in 12-month old 3xTg mice using streptozotocin (STZ; 90mg/kg, i.p., on two successive days). Hyperglycemia was verified by sampling blood glucose levels. Three months after injection (at 15 months of age), the mice were behaviorally tested in the Morris water maze and contextual fear conditioning. Subsequently, the hippocampal region was examined using immunohistochemistry (6E10 antibody for amyloid) and immunoblotting (AT8 antibody for phosphorylated tau). No differences were found in learning or memory between the vehicle-treated control and STZ-treated groups. A significant increase in the number of amyloid-positive plaques was observed in the subiculum of STZ-treated mice; very few plaques were seen in other hippocampal regions in either group. No differences in AT8 load were observed. These results reinforce that amyloid plaques, per se, are not sufficient to cause memory impairments. Further, while diabetes can enhance this aspect of brain pathology, the combination of disrupted glucose metabolism and the transgenes is still not sufficient to cause the severe cognitive impairments associated with clinical AD.
authors.affiliation: Department of Physiology, School of Medicine, Southern Illinois University Carbondale, IL 62901, USA; Neuroscience Research Center, Southern Illinois University Carbondale, IL 62901, USA.
authors.forename: Emi
authors.initials: E
authors.lastname: Hayashi-Park
authors.affiliation: Department of Anatomy, School of Medicine, Southern Illinois University Carbondale, IL 62901, USA; Neuroscience Research Center, Southern Illinois University Carbondale, IL 62901, USA.
authors.forename: Bria N
authors.initials: BN
authors.lastname: Ozment
authors.affiliation: Department of Physiology, School of Medicine, Southern Illinois University Carbondale, IL 62901, USA; Neuroscience Research Center, Southern Illinois University Carbondale, IL 62901, USA.
authors.forename: Chelsea M
authors.initials: CM
authors.lastname: Griffith
authors.affiliation: Department of Anatomy, School of Medicine, Southern Illinois University Carbondale, IL 62901, USA; Neuroscience Research Center, Southern Illinois University Carbondale, IL 62901, USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, School of Medicine, Southern Illinois University Carbondale, IL 62901, USA; Department of Physiology, School of Medicine, Southern Illinois University Carbondale, IL 62901, USA; Neuroscience Research Center, Southern Illinois University Carbondale, IL 62901, USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Patrylo
authors.affiliation: Department of Anatomy, School of Medicine, Southern Illinois University Carbondale, IL 62901, USA; Department of Physiology, School of Medicine, Southern Illinois University Carbondale, IL 62901, USA; Neuroscience Research Center, Southern Illinois University Carbondale, IL 62901, USA. Electronic address: grose@siumed.edu.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Rose
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D007150:Immunohistochemistry; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D008822:Mice, Transgenic; D009483:Neuropsychological Tests; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C558298:Mapt protein, mouse; D016875:tau Proteins
keywords: 3xTg; Alzheimer; Diabetes; Streptozotocin; Triple transgenic