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

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

doi:10.3390/ijms18040800

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.

Highlights

The basic unit of information transmission between neurons is the synapse, which is composed of dendritic spines on the surface of dendrites and plays an important role in learning and memory [1,2]
Studies report that Dbn depletion in wild-type mice reduced the dopamine receptor D1 (D1R), dopamine receptor D2 (D2R), 5-hydroxytryptamine receptor 1A (5-HT1AR), and 5-hydroxytryptamine receptor 7 (5-HT7R) protein levels in the hippocampus
That was rarely reported in transgenic mice, and behavioral activities, cerebral glucose metabolism, or other indexes were rarely studied [2]

Summary

Introduction

The basic unit of information transmission between neurons is the synapse, which is composed of dendritic spines on the surface of dendrites and plays an important role in learning and memory [1,2]. Dbn A (referred to as Dbn in mice) has been found in the function of maintaining long-term memory in vitro and is distributed in the neurons of the brain, especially in dendritic spines [5,6]. It has been found that Dbn is an F-actin binding protein, which conducts polymerization and depolymerization with F-actin to maintain or interrupt memory activities [7,8]. Studies report that Dbn depletion in wild-type mice reduced the dopamine receptor D1 (D1R), dopamine receptor D2 (D2R), 5-hydroxytryptamine receptor 1A (5-HT1AR), and 5-hydroxytryptamine receptor 7 (5-HT7R) protein levels in the hippocampus. A noticeable reduction in memory-related hippocampal synaptic plasticity was found in electrophysiological studies of Dbn depleted mice. That was rarely reported in transgenic mice, and behavioral activities, cerebral glucose metabolism, or other indexes were rarely studied [2]

Methods

Results

Conclusion