title: Object recognition memory and BDNF expression are reduced in young TgCRND8 mice.
abstract: The TgCRND8 mouse model of Alzheimer's disease exhibits progressive cortical and hippocampal β-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.
authors.affiliation: Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
authors.forename: Beverly M
authors.initials: BM
authors.lastname: Francis
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.forename: Meredith E
authors.initials: ME
authors.lastname: Barakat
authors.forename: Stephan
authors.initials: S
authors.lastname: Fraenkl
authors.forename: Yeni H
authors.initials: YH
authors.lastname: Yücel
authors.forename: Shiyong
authors.initials: S
authors.lastname: Peng
authors.forename: Bernadeta
authors.initials: B
authors.lastname: Michalski
authors.forename: Margaret
authors.initials: M
authors.lastname: Fahnestock
authors.forename: Joanne
authors.initials: J
authors.lastname: McLaurin
authors.forename: Howard T J
authors.initials: HT
authors.lastname: Mount
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D006224:Cricetinae; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics*; D005625:Frontal Lobe / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D008647:Mesocricetus; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger
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