Brain-Derived Neurotrophic Factor Precursor in the Hippocampus Regulates Both Depressive and Anxiety-Like Behaviors in Rats.

Feng Zhong,Zhao-Lan Hu,Jun-Mei Xu,Chang-Qi Li,Shuang Wang,Lei Liu,Zhao-Yun Yang,Ru-Ping Dai,Jia-Li Wei,Xin-Fu Zhou,Li Li

doi:10.3389/fpsyt.2018.00776

Abstract

Depression and anxiety are two affective disorders that greatly threaten the mental health of a large population worldwide. Previous studies have shown that brain-derived neurotrophic factor precursor (proBDNF) is involved in the development of depression. However, it is still elusive whether proBDNF is involved in anxiety, and if so, which brain regions of proBDNF regulate these two affective disorders. The present study aims to investigate the role of proBDNF in the hippocampus in the development of depression and anxiety. Rat models of an anxiety-like phenotype and depression-like phenotype were established by complete Freund's adjuvant intra-plantar injection and chronic restraint stress, respectively. Both rat models developed anxiety-like behaviors as determined by the open field test and elevated plus maze test. However, only rats with depression-like phenotype displayed the lower sucrose consumption in the sucrose preference test and a longer immobility time in the forced swimming test. Sholl analysis showed that the dendritic arborization of granule cells in the hippocampus was decreased in rats with depression-like phenotype but was not changed in rats with anxiety-like phenotype. In addition, synaptophysin was downregulated in the rats with depression-like phenotype but upregulated in the rats with anxiety-like phenotype. In both models, proBDNF was greatly increased in the hippocampus. Intra-hippocampal injection anti-proBDNF antibody greatly ameliorated the anxiety-like and depressive behaviors in the rats. These findings suggest that despite some behavioral and morphological differences between depression and anxiety, hippocampal proBDNF is a common mediator to regulate these two mental disorders.

Highlights

Depression and anxiety are highly debilitating mental disorders that severely affect patients’ quality of life and put a burden on families and society
Both rats treated with complete Freund’s adjuvant (CFA) and those treated with chronic restraint stress (CRS) displayed decreased traveled distance in the central square in the OFT (Figure 1D) and reduced time spent in the open arms in the EPM (Figure 1E)
The SPT results showed that CFA-treated rats had comparable sucrose consumption with the controls whereas CRS-treated rats consumed less sucrose than both the controls and CFA-treated rats (Figure 1F)

Summary

Introduction

Depression and anxiety are highly debilitating mental disorders that severely affect patients’ quality of life and put a burden on families and society. Depression ranks as the largest contributor to global disability and nearly 300 million people suffer from anxiety. Around half of them have comorbidity of depression and anxiety [1, 2]. Studies on depression and anxiety proBDNF Regulates Depression and Anxiety mechanisms and the invention of therapeutic drugs develop slowly. Clinical drugs take weeks to months to have therapeutic effects, while more than one-third of patients are still resistant to the treatment [3]. It is urgent to explore the underlying mechanism of depression and anxiety

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