Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson's disease.

Olga Lopatina,Andrei Sumarokov,Yulia Petugina,Shigeru Yokoyama,Koji Hashida,Tomoko Nishimura,Shirin Akther,Mingkun Liang,Yuki Inahata,Azam A K M Fakhrul,Fangfang Zhong,Osamu Hori,Yasuko Kitao,Kazuhiro Shiba,Kazumi Furuhara,Chiharu Higashida,Masahide Asano,Katsuhiko Ishihara,Haruhiro Higashida,Keita Koizumi,Kohei Sumi,Takashi Kozaka,Makoto Sato,Jing Zhong,Takahiro Tsuji,Yoshihisa Kitamura ,А Б Салмина ,Toshio Yoshihara ,Min Xie ,J J Huang

doi:10.3389/fnbeh.2014.00133

Abstract

CD157, known as bone marrow stromal cell antigen-1, is a glycosylphosphatidylinositol-anchored ADP-ribosyl cyclase that supports the survival and function of B-lymphocytes and hematopoietic or intestinal stem cells. Although CD157/Bst1 is a risk locus in Parkinson's disease (PD), little is known about the function of CD157 in the nervous system and contribution to PD progression. Here, we show that no apparent motor dysfunction was observed in young knockout (CD157−/−) male mice under less aging-related effects on behaviors. CD157−/− mice exhibited anxiety-related and depression-like behaviors compared with wild-type mice. These behaviors were rescued through treatment with anti-psychiatric drugs and oxytocin. CD157 was weakly expressed in the amygdala and c-Fos immunoreactivity in the amygdala was less evident in CD157−/− mice than in wild-type mice. These results demonstrate for the first time that CD157 plays a role as a neuro-regulator and suggest a potential role in pre-motor symptoms in PD.

Highlights

Parkinson’s disease (PD) is considered to be a movement disorder, and its diagnosis is based on the presence of a set of cardinal motor symptoms (Samil et al, 2004; Jankovic, 2008)
Considerable evidence has shown that the neurodegenerative processes that lead to sporadic PD begin many years before the appearance of the characteristic motor symptoms associated with nigro-striatal dopaminergic neuron loss (Leentjens et al, 2011; Noyce et al, 2012; Prediger et al, 2012)
When 8- to 10-week-old CD157+/+ and CD157−/− male mice were subjected to the rota rod test for 3 successive days, there were no differences in their motor coordination and learning (Figure 1B)

Summary

Introduction

Parkinson’s disease (PD) is considered to be a movement disorder, and its diagnosis is based on the presence of a set of cardinal motor symptoms (Samil et al, 2004; Jankovic, 2008). Genome-wide association studies and meta-analysis for PD have identified intronic single-nucleotide polymorphisms (SNPs) in the CD157/BST1 gene on human chromosome 4p15 as new susceptibility loci in several populations (Satake et al, 2009; Tan et al, 2010; Liu et al, 2011, 2013b; Nalls et al, 2011; Saad et al, 2011; Simón-Sánchez et al, 2011; Spencer et al, 2011; Zimprich, 2011; Lill et al, 2012; Sharma et al, 2012), with reported variations (Chang et al, 2011; Miyake et al, 2012; Wang et al, 2012; Zhu et al, 2012; Chen et al, 2013; Chung et al, 2013) These studies indicate that CD157 might be associated with the causality of PD, or at least one of a variety of PD symptoms

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Results

Conclusion