Mol.Psy.:与精神分裂症发病机制相关的蛋白质
新华网 · 2010/07/12
日本爱知县身心障碍者精神发育障碍研究所日前宣布,该所研究人员发现了与精神分裂症发病有关的一种蛋白质的功能,从而弄清了此病的发病机制。 精神分裂症是以幻觉和妄想为症状的精神疾病。虽然神经传导物质分泌异常和脑神经发育障碍被认为是致病原因,但是研究人员过去一直没有弄清详细的发病机制。

日本爱知县身心障碍者精神发育障碍研究所日前宣布,该所研究人员发现了与精神分裂症发病有关的一种蛋白质的功能,从而弄清了此病的发病机制。

精神分裂症是以幻觉和妄想为症状的精神疾病。虽然神经传导物质分泌异常和脑神经发育障碍被认为是致病原因,但是研究人员过去一直没有弄清详细的发病机制。

在本次研究中,研究人员发现,蛋白质“Dysbindin-1”与精神分裂症发病有关,这种蛋白质存在于负责脑神经细胞间信息交换的“突触”中。

研究人员通过老鼠实验发现,减少“Dysbindin-1”蛋白质的含量,在“突触”中接受信息的组织就无法正常发育,从而导致精神分裂症。反之,如果补充这种蛋白质,有关组织的机能就会得到恢复。

有关论文已刊登在英国《分子精神病学》网络版上。

 

推荐原文出处:

Molecular Psychiatry doi: 10.1038/mp.2010.69

Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation

H Ito1, R Morishita1, T Shinoda1, I Iwamoto1, K Sudo1, K-I Okamoto1 and K Nagata1

1Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan

Genetic variations in dysbindin-1 (dystrobrevin-binding protein-1) are one of the most commonly reported variations associated with schizophrenia. As schizophrenia could be regarded as a neurodevelopmental disorder resulting from abnormalities of synaptic connectivity, we attempted to clarify the function of dysbindin-1 in neuronal development. We examined the developmental change of dysbindin-1 in rat brain by western blotting and found that a 50?kDa isoform is highly expressed during the embryonic stage, whereas a 40?kDa one is detected at postnatal day 11 and increased thereafter. Immunofluorescent analyses revealed that dysbindin-1 is enriched at the spine-like structure of primary cultured rat hippocampal neurons. We identified WAVE2, but not N-WASP, as a binding partner for dysbindin-1. We also found that Abi-1, a binding molecule for WAVE2 involved in spine morphogenesis, interacts with dysbindin-1. Although dysbindin-1, WAVE2 and Abi-1 form a ternary complex, dysbindin-1 promoted the binding of WAVE2 to Abi-1. RNA interference-mediated knockdown of dysbindin-1 led to the generation of abnormally elongated immature dendritic protrusions. The present results indicate possible functions of dysbindin-1 at the postsynapse in the regulation of dendritic spine morphogenesis through the interaction with WAVE2 and Abi-1.

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