Changes in expression of BDNF and its receptors TrkB and p75NTR in the hippocampus of a dog model of chronic alcoholism and abstinence.

R. Xu,J.W. Zhao,S.R. Duan,C.Y. Wang

doi:10.1590/1414-431x20154412

Abstract

Chronic ethanol consumption can produce learning and memory deficits. Brain-derived neurotrophic factor (BDNF) and its receptors affect the pathogenesis of alcoholism. In this study, we examined the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence. Twenty domestic dogs (9-10 months old, 15-20 kg; 10 males and 10 females) were obtained from Harbin Medical University. A stable alcoholism model was established through ad libitum feeding, and anti-alcohol drug treatment (Zhong Yao Jie Jiu Ling, the main ingredient was the stems of watermelon; developed in our laboratory), at low- and high-doses, was carried out. The Zhong Yao Jie Jiu Ling was effective for the alcoholism in dogs. The morphology of hippocampal neurons was evaluated using hematoxylin-eosin staining. The number and morphological features of BDNF, TrkB and p75NTR-positive neurons in the dentate gyrus (DG), and the CA1, CA3 and CA4 regions of the hippocampus were observed using immunohistochemistry. One-way ANOVA was used to determine differences in BDNF, TrkB and p75NTR expression. BDNF, TrkB and p75NTR-positive cells were mainly localized in the granular cell layer of the DG and in the pyramidal cell layer of the CA1, CA3 and CA4 regions (DG>CA1>CA3>CA4). Expression levels of both BDNF and TrkB were decreased in chronic alcoholism, and increased after abstinence. The CA4 region appeared to show the greatest differences. Changes in p75NTR expression were the opposite of those of BDNF and TrkB, with the greatest differences observed in the DG and CA4 regions.

Highlights

Chronic ethanol consumption can negatively affect central nervous system function and produce learning and memory impairment in animals and humans [1,2,3]
We examined the expression of Brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence
BDNF, TrkB and p75NTR-positive cells in the hippocampus were mainly localized in the granular cell layer of the dentate gyrus (DG) and the pyramidal cell layer of the CA1, CA3 and CA4 regions

Summary

Introduction

Chronic ethanol consumption can negatively affect central nervous system function and produce learning and memory impairment in animals and humans [1,2,3]. The hippocampus, a region important for memory function, can recover from memory dysfunction caused by prolonged ethanol intake [4,5,6,7]. Chronic ethanol consumption may play a role in the expression of neurotrophins and their receptors, or interfere with neural signal transduction pathways involving these proteins [11]. Compared with other neurotrophic factors, BDNF may be directly involved in the development and pathogenesis of alcohol dependence [19,20,21,22]. It has been reported that the BDNF gene locus is associated with alcohol use [23], and even moderate ethanol intake can increase expression levels of BDNF [24].

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Conclusion