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

An immunohistochemical, enzymatic, and behavioral study of CD157/BST-1 as a neuroregulator.
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DOI:
10.1186/s12868-017-0350-7
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发表时间:
2017-03-24
期刊:
影响因子:
2.4
通讯作者:
Lopatina O
Lopatina O
中科院分区:
医学4区
文献类型:
--
作者:
Higashida H;Liang M;Yoshihara T;Akther S;Fakhrul A;Stanislav C;Nam TS;Kim UH;Kasai S;Nishimura T;Al Mahmuda N;Yokoyama S;Ishihara K;Gerasimenko M;Salmina A;Zhong J;Tsuji T;Tsuji C;Lopatina O

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最近的啮齿动物和人类研究提供的证据支持这样一个事实,即CD 157,众所周知的骨髓基质细胞抗原-1(BST-1)和帕金森病的危险因素,也有意义地在大脑中作为神经调节剂发挥作用并影响社会行为。研究表明,在没有严重运动功能障碍的CD 157基因敲除小鼠中,社会行为受损,并且CD 157/BST 1基因单核苷酸多态性与人类自闭症谱系障碍相关。然而,仍然有必要确定这种分子如何有助于大脑的生理和病理生理功能。为了获得关于脑中CD 157的存在及其酶活性与异常社会行为之间关系的新见解,对不同年龄的CD 157敲除小鼠进行了测试。在E17胚胎的脑室区,CD 157免疫反应与巢蛋白阳性细胞和元素共定位。新生儿脑CD 157 mRNA水平较高,但成人较低。在成人大脑的几个区域,包括杏仁核,检测到了微弱但明显的免疫反应性。CD 157具有很少或没有碱基交换活性,但具有一定的ADP-核糖基环化酶活性,表明CD 157形成环状ADP-核糖,但形成更少的烟酸腺嘌呤二核苷酸磷酸,两者都从细胞内Ca 2+池中动员Ca 2+。CD 157基因敲除小鼠的社交回避通过单次腹腔注射催产素来拯救。CD 157可能在胚胎和成人神经系统中发挥作用。CD 157的功能特征可以部分地通过产生环状ADP-核糖而不是烟酸腺嘌呤二核苷酸磷酸来解释。需要进一步的实验来阐明胚胎期神经干细胞中CD 157的表达如何影响成年人的行为或精神症状。本文的在线版本(doi:10.1186/s12868-017-0350-7)包含补充材料,可供授权用户使用。
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, 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. To 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. CD157 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. CD157 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. The online version of this article (doi:10.1186/s12868-017-0350-7) contains supplementary material, which is available to authorized users.