Object recognition memory and BDNF expression are reduced in young TgCRND8 mice

NEUROBIOLOGY OF AGING

卷:33

Article

Francis, Beverly M.^1,2  Kim, John^1,2  Barakat, Meredith E.^2,3  Fraenkl, Stephan^3,4  Yuecel, Yeni H.^3,4  Peng, Shiyong⁵  Michalski, Bernadeta⁵  Fahnestock, Margaret⁵  McLaurin, JoAnne^2,3  Mount, Howard T. J.^1,2,6 

[1] Univ Toronto, Dept Physiol, Toronto, ON M5S 3H2, Canada

[2] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON M5S 3H2, Canada

[3] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 3H2, Canada

[4] Univ Toronto, Dept Ophthalmol & Vis Sci, Keenan Res Ctr, Li Ka Shing Knowledge Inst,St Michaels Hosp, Toronto, ON M5S 3H2, Canada

[5] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada

[6] Univ Toronto, Dept Med, Div Neurol, Toronto, ON M5S 3H2, Canada

关键词: Alzheimer's disease;    Object recognition memory;    Entorhinal cortex;    Hippocampus;    Morris water maze;    Optokinetic responses;    TgCRND8 mice;    Spatial memory;    Amyloid precursor protein (APP);    Brain-derived neurotrophic factor (BDNF);    Real Time RT-PCR;   

DOI  :  10.1016/j.neurobiolaging.2010.04.003

来源: Elsevier

【 摘 要 】

The TgCRND8 mouse model of Alzheimer's disease exhibits progressive cortical and hippocampal beta-amyloid accumulation, resulting in plaque pathology and spatial memory impairment by 3 months of age. We tested whether TgCRND8 cognitive function is disrupted prior to the appearance of macroscopic plaques in an object recognition task. We found profound deficits in 8-week-old mice. Animals this age were not impaired on the Morris water maze task. TgCRND8 and littermate controls did not differ in their duration of object exploration or optokinetic responses. Thus, visual and motor dysfunction did not confound the phenotype. Object memory deficits point to the frontal cortex and hippocampus as early targets of functional disruption. Indeed, we observed altered levels of brain-derived neurotrophic factor (BDNF) messenger ribonucleic acid (mRNA) in these brain regions of preplaque TgCRND8 mice. Our findings suggest that object recognition provides an early index of cognitive impairment associated with amyloid exposure and reduced brain-derived neurotrophic factor expression in the TgCRND8 mouse. (C) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

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