Down-Regulated Drebrin Aggravates Cognitive Impairments in a Mouse Model of Alzheimer’s DiseaseReportar como inadecuado


Down-Regulated Drebrin Aggravates Cognitive Impairments in a Mouse Model of Alzheimer’s Disease


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Comparative Medicine Center, Peking Union Medical College PUMC and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences CAMS, Beijing 100021, China





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Academic Editor: Katalin Prokai-Tatrai

Abstract The developmentally regulated brain protein drebrin Dbn is a functional protein involved with long-term memory formation and is widely distributed in brain neurons, especially in the dendritic spines. A noticeable decline of this protein has been found in the hippocampus and cortex of patients with Alzheimer’s disease AD, yet the relationship between Dbn and AD has not been fully understood. In the present study, we examined how down-regulation of Dbn impacts the progression of AD in experimental animals. Accordingly, we injected Dbn interference vector rAAV-mDbn1 ShRNA into the hippocampus of three-month old APPswe-PS1ΔE9 mice APP-PS1 mice and then successfully down-regulated Dbn expression in this brain region. Behavioral tests, including the Morris water maze test, the open field test, and the novel object test were conducted when the animals were nine months old. Subsequently, MicroPET-CT imaging to monitor glucose metabolism was done. We then investigated Aβ, GFAP, PSD-95, MAP2, vimentin, Cox43, and Syn1 expressions in the brain of the experimental animals via immunohistochemical or immunofluorescence methods. We found that AD mice with a low expression of Dbn performed poorly in the behavioral tests and showed decreased glucose utilization. In the brains of these animals, we detected a slight increase of Aβ, GFAP and vimentin and a significant decline of PSD-95. Altogether our data warrant further studies to elucidate the effect of Dbn on the development and progression of AD. View Full-Text

Keywords: drebrin; Alzheimer’s disease; cognitive ability; hippocampus; APP-PS1 mice drebrin; Alzheimer’s disease; cognitive ability; hippocampus; APP-PS1 mice





Autor: Yan Liu, Yanfeng Xu, Ling Zhang, Lan Huang, Pin Yu, Hua Zhu, Wei Deng and Chuan Qin *

Fuente: http://mdpi.com/



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