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Age-Related Neuronal Deterioration Specifically Within the Dorsal CA1 Region of the Hippocampus 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 & Molecular Sciences, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada.
  • Bennett BM; Department of Biomedical & Molecular Sciences, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada.
  • Andrew RD; Department of Biomedical & Molecular Sciences, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada.
J Alzheimers Dis ; 79(4): 1547-1561, 2021.
Article em En | MEDLINE | ID: mdl-33459722
BACKGROUND: Neuronal damage resulting from increased oxidative stress is important in the development of late onset/age-related Alzheimer's disease (LOAD). We have developed an oxidative stress-related mouse model of LOAD based on gene deletion of aldehyde dehydrogenase 2 (ALDH2), an enzyme important for the detoxification of endogenous aldehydes arising from lipid peroxidation. Compared to wildtype (WT) mice, the knockout (KO) mice exhibit AD-like pathologies and a progressive decline in recognition and spatial memory. This progression presumably has a morphological basis induced by oxidative damage. OBJECTIVE: We performed morphometric analyses in the dorsal hippocampal CA1 region (dCA1) to determine if altered neuronal structure can help account for the progressive cognitive impairment in 3- to 12-month-old KO mice. METHODS: Dendritic morphology was quantitatively analyzed by branched structured analysis and Sholl analysis following Golgi-Cox staining in WT mice (148 neurons) versus KO mice (180 neurons). RESULTS: The morphology and complexity of dCA1 pyramidal neurons were similar at age 3 months in WTs and KOs. However, by 6 months there were significant reductions in apical and basal dendritic length, dendrite complexity, and spine density in KO versus WT mice that were maintained through ages 9 and 12 months. Immunostaining for protein adducts of the lipid peroxidation product 4-hydroxynonenal revealed significant increases in staining in dCA1 (but not ventral CA1) by 3 months, increasing through 12 months. CONCLUSION: This specific and progressive increase in dCA1 oxidative damage preceded detectable synaptic trimming in KO mice, in keeping with studies showing that lesions to dorsal hippocampus primarily impair cognitive memory.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Região CA1 Hipocampal / Doença de Alzheimer / Neurônios Limite: Animals Idioma: En Revista: J Alzheimers Dis Assunto da revista: GERIATRIA / NEUROLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Região CA1 Hipocampal / Doença de Alzheimer / Neurônios Limite: Animals Idioma: En Revista: J Alzheimers Dis Assunto da revista: GERIATRIA / NEUROLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Canadá