An immunohistochemical, enzymatic, and behavioral study of CD157/BST-1 as a neuroregulator

Haruhiro Higashida,Cherepanov Stanislav,Katsuhiko Ishihara,Olga Lopatina,Naila Al Mahmuda,Maria Gerasimenko,Tae-Sik Nam,Azam Fakhrul,Satoka Kasai,Tomoko Nishimura,Toru Yoshihara,Takahiro Tsuji,Shigeru Yokoyama,Chiharu Tsuji,Uh-Hyun Kim,Shirin Akther,Jing Zhong,Mingkun Liang,Alla Salmina

doi:10.1186/s12868-017-0350-7

Abstract

BackgroundRecent rodent and human studies provide evidence in support of the fact that CD157, well known as bone marrow stromal cell antigen-1 (BST-1) and a risk factor in Parkinson’s disease, also meaningfully acts in the brain as a neuroregulator and affects social behaviors. It has been shown that social behaviors are impaired in CD157 knockout mice without severe motor dysfunction and that CD157/BST1 gene single nucleotide polymorphisms are associated with autism spectrum disorder in humans. However, it is still necessary to determine how this molecule contributes to the brain’s physiological and pathophysiological functions.MethodsTo gain fresh insights about the relationship between the presence of CD157 in the brain and its enzymatic activity, and aberrant social behavior, CD157 knockout mice of various ages were tested.ResultsCD157 immunoreactivity colocalized with nestin-positive cells and elements in the ventricular zones in E17 embryos. Brain CD157 mRNA levels were high in neonates but low in adults. Weak but distinct immunoreactivity was detected in several areas in the adult brain, including the amygdala. CD157 has little or no base exchange activity, but some ADP-ribosyl cyclase activity, indicating that CD157 formed cyclic ADP-ribose but much less nicotinic acid adenine dinucleotide phosphate, with both mobilizing Ca2+ from intracellular Ca2+ pools. Social avoidance in CD157 knockout mice was rescued by a single intraperitoneal injection of oxytocin.ConclusionsCD157 may play a role in the embryonic and adult nervous systems. The functional features of CD157 can be explained in part through the production of cyclic ADP-ribose rather than nicotinic acid adenine dinucleotide phosphate. Further experiments are required to elucidate how the embryonic expression of CD157 in neural stem cells contributes to behaviors in adults or to psychiatric symptoms.

Highlights

Recent rodent and human studies provide evidence in support of the fact that CD157, well known as bone marrow stromal cell antigen-1 (BST-1) and a risk factor in Parkinson’s disease, meaningfully acts in the brain as a neuroregulator and affects social behaviors
We used polyclonal antiserum raised in rabbits against a chimeric fusion protein of murine CD157 that had been preabsorbed with CD38, to examine its specificity for CD157
In C57BL/6N wild-type adult mice, CD157 immunoreactivity was shown in the white pulp region of the spleen, where CD157 was enriched (CD157+/+, Fig. 1), while no staining was observed in CD157 knockout (CD157−/−) mice

Summary

Introduction

Recent rodent and human studies provide evidence in support of the fact that CD157, well known as bone marrow stromal cell antigen-1 (BST-1) and a risk factor in Parkinson’s disease, meaningfully acts in the brain as a neuroregulator and affects social behaviors. CD157, discovered as bone marrow stromal cell antigen-1 (BST-1) by Hirano and colleagues [14,15,16], is a cell-surface molecule that supports pre-B cell growth with enhanced expression on bone marrow stromal cell lines derived from rheumatoid arthritis patients [17]. BST-1, expressed by myeloid cells as a molecule capable of signal transduction, was clustered as CD157 after gene cloning [14, 17]. Its involvement in rheumatoid arthritis was implicated in the study that reported its discovery [17]. The expression of CD157 in ovarian carcinoma cells is an indicator of malignancy and a higher rate of metastasis [18]

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