ErbB4 localization to interneurons: clearer insights into schizophrenia pathology.
ErbB4 localization to interneurons: clearer insights into schizophrenia pathology.
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ERBB4与中间神经元的定位：对精神分裂症病理学的更清晰见解。
DOI：
10.1016/j.biopsych.2011.08.002
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发表时间：
2011-10-01
影响因子：
10.6
通讯作者：
Koleske, Anthony J.
中科院分区：
文献类型：
--
作者：
Cooper, Margaret A.;Koleske, Anthony J.
精神分裂症是最具遗传性的精神疾病之一，对受影响家庭的单倍型筛选发现了与这种疾病相关的几个基因，包括编码神经调节蛋白-1（NRG 1）的基因（1）。NRG 1和受体酪氨酸激酶ErbB 4通过其发挥作用，对神经系统发育至关重要。ErbB 4启动下游信号传导事件，控制神经元祖细胞增殖、神经节隆起的中间神经元迁移、神经元能神经元的径向迁移、少突胶质细胞发育和髓鞘形成以及成人突触可塑性（2）。有趣的是，精神分裂症患者的大脑中也有许多相同的过程被破坏，精神分裂症患者的大脑在死后通常会显示出皮质锥体神经元树突棘密度相对于对照组的减少。许多离散的可能机制可能是这种脊柱丢失的基础。事实上，精神分裂症的分子和细胞病理学涉及多巴胺能和多巴胺能神经递质释放的失调以及N-甲基-D-天冬氨酸（NMDA）受体功能低下，所有这些最终都可能导致青春期突触连接的丧失。
Schizophrenia is one of the most heritable psychiatric disorders, and haplotype screens of affected families have uncovered several genes linked to this disorder, including the gene encoding neuregulin-1 (NRG1)(1). NRG1 and the receptor tyrosine kinase, ErbB4, through which it exerts is actions, are critical for nervous system development. ErbB4 initiates downstream signaling events that control neuronal progenitor proliferation, interneuron migration from the ganglionic eminences, radial migration of glutamatergic neurons, oligodendrocyte development, and myelination as well as synaptic plasticity in the adult (2). Interestingly, many of these same processes are disrupted in schizophrenia.Postmortem brains from patients affected by schizophrenia often show a decrease in dendritic spine density on cortical pyramidal neurons relative to control subjects. A number of discrete possible mechanisms may underlie this spine loss. Indeed, the molecular and cellular pathology of schizophrenia involves the misregulation of both glutamatergic and dopaminergic neurotransmitter release and N-methyl-D-aspartate (NMDA) receptor hypofunction, all of which could ultimately contribute to the loss of synaptic connections during adolescence.
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