title: Down-Regulated Drebrin Aggravates Cognitive Impairments in a Mouse Model of Alzheimer's Disease.
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 ofDbnimpacts the progression of AD in experimental animals. Accordingly, we injectedDbninterference vector (rAAV-mDbn1ShRNA) into the hippocampus of three-month old APP(swe)/PS1(ΔE9) mice (APP/PS1 mice) and then successfully down-regulatedDbnexpression 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.
authors.affiliation: Comparative Medicine Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China. sdcssm@sina.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Comparative Medicine Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China. xuyanf2009@163.com.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Comparative Medicine Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China. zhangling@cnilas.org.cn.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Comparative Medicine Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China. huanglan0204@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.affiliation: Comparative Medicine Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China. pinyucau@gmail.com.
authors.forename: Pin
authors.initials: P
authors.lastname: Yu
authors.affiliation: Comparative Medicine Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China. zhuhua0226@vip.sina.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Comparative Medicine Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China. dengwei717@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: Comparative Medicine Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China. qinchuan@pumc.edu.cn.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D000076122:Disks Large Homolog 4 Protein; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014746:Vimentin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D009479:Neuropeptides; D014746:Vimentin; C053386:drebrins; D051528:Guanylate Kinases
keywords: APP/PS1 mice; Alzheimer’s disease; cognitive ability; drebrin; hippocampus