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Int. J. Mol. Sci. 2017, 18(4), 800; doi:10.3390/ijms18040800

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

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
Received: 1 March 2017 / Revised: 30 March 2017 / Accepted: 1 April 2017 / Published: 11 April 2017
(This article belongs to the Special Issue Neuroprotective Strategies 2017)
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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 APP(swe)/PS1(ΔE9) 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
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Liu, Y.; Xu, Y.; Zhang, L.; Huang, L.; Yu, P.; Zhu, H.; Deng, W.; Qin, C. Down-Regulated Drebrin Aggravates Cognitive Impairments in a Mouse Model of Alzheimer’s Disease. Int. J. Mol. Sci. 2017, 18, 800.

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