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Morphometric Analysis of Hippocampal and Neocortical Pyramidal Neurons in a Mouse Model of Late Onset Alzheimer's Disease.
Mehder, Rasha H; Bennett, Brian M; Andrew, R David.
Afiliação
  • Mehder RH; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
  • Bennett BM; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
  • Andrew RD; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
J Alzheimers Dis ; 74(4): 1069-1083, 2020.
Article em En | MEDLINE | ID: mdl-32144984
The study of late-onset (sporadic) Alzheimer's disease (LOAD) has lacked animal models where impairments develop with aging. Oxidative stress promotes LOAD, so we have developed an oxidative stress-based model of age-related cognitive impairment based on gene deletion of aldehyde dehydrogenase 2 (ALDH2). This enzyme is important for the detoxification of endogenous aldehydes arising from lipid peroxidation. Compared to wildtype (WT) mice, the knockout (KO) mice exhibit a progressive decline in recognition and spatial memory and AD-like pathologies. Here we performed morphometric analyses in the dorsal and ventral hippocampal CA1 regions (dCA1 and vCA1) as well as in overlying primary sensory cortex to determine if altered neuronal structure can help account for the cognitive impairment in 12-month old KO mice. Dendritic morphology was quantitatively analyzed following Golgi-Cox staining using 9 WT mice (108 neurons) and 15 KO mice (180 neurons). Four pyramidal neurons were traced per mouse in each region, followed by branched structured analysis and Sholl analysis. Compared to WT controls, the morphology and complexity of dCA1 pyramidal neurons from KOs showed significant reductions in apical and basal dendritic length, dendrite intersections, ends, and nodes. As well, spine density along dorsal CA1 apical dendrites was significantly lower in KO versus WT. In contrast, pyramidal arborization in the vCA1 and primary sensory cortex were only minimally reduced in KO versus WT mice. These data suggest a region-specific vulnerability to oxidative stress-induced damage and/or a major and specific reduction in synaptic input to the pyramidal neurons of the dorsal hippocampus. This is in keeping with studies showing that lesions to the dorsal hippocampus impair primarily cognitive memory whereas ventral hippocampal lesions cause deficits in stress, emotion, and affect.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Piramidais / Neocórtex / Doença de Alzheimer / Hipocampo Limite: Animals Idioma: En Revista: J Alzheimers Dis Assunto da revista: GERIATRIA / NEUROLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Piramidais / Neocórtex / Doença de Alzheimer / Hipocampo Limite: Animals Idioma: En Revista: J Alzheimers Dis Assunto da revista: GERIATRIA / NEUROLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Canadá