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首页> 外文期刊>Stem Cell Discovery >NSC-induced D-neurons are decreased in striatum of schizophrenia: Possible cause of mesolimbic dopamine hyperactivity
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NSC-induced D-neurons are decreased in striatum of schizophrenia: Possible cause of mesolimbic dopamine hyperactivity

机译：NSC诱导的D神经元在精神分裂症的纹状体中减少：中脑边缘多巴胺活动亢进的可能原因

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Neural stem cell (NSC) hypofunction is an etiological hypothesis of schizophrenia. Although dopamine (DA) dysfunction is also a widely accepted hypothesis, molecular background of mesolimbic DA hyperactivity has not yet been well known. Here, the author proposes “D-cell hypothesis”, accounting for molecular basis of mesolimbic DA hyperactivity of schizophrenia, by NSC hypofunction and decrease of putative NSC-induced D-cells. The “D-cell” is defined as “non-monoaminergic aromatic L-amino acid decarboxylase (AADC)-containing cell”. D-cells produce trace amines, and also take up amine precursors and convert them to amines by decarboxylation. The author reported “dopa-decarboxylating neurons specific to the human striatum”, that is, “D-neurons” in the human striatum, and decrease of striatal D-neurons in patients with schizophrenia. Trace amine-associated receptor, type 1 (TAAR1), a subtype of trace amine receptors, having a quite number of ligands such as tyramine, β-phenylethylamine (PEA) and methamphetamine, has modulating functions on monoamine neurons. It has been known that reduced binding of ligands to TAAR1 receptors on DA terminal of DA neurons of the midbrain ventral tegmental area (VTA) increased firing frequency of VTA DA neurons. In brains of schizophrenia, NSC hypofunction in the subventricular zone of lateral ventricle may cause decrease of D-neurons in the striatum and nucleus accumbens, and may result in decrease of trace amine signals. Decrease of trace amine signals to TAAR1 on VTA DA neurons may increase firing frequency of VTA DA neurons, and may finally cause mesolimbic DA hyperactivity. Increased stimulation to DA D2 receptors of NSCs might suppress NSC proliferation, and may induce additional mesolimbic DA hyperactivity as well as D-cell decrease. This novel theory, “D-cell hypothesis”, possibly explains mesolimbic DA hyperactivity in pathogenesis of schizophrenia.
机译：神经干细胞（NSC）功能减退是精神分裂症的病因学假设。尽管多巴胺（DA）功能障碍也是公认的假说，但中脑边缘DA过度活跃的分子背景尚未广为人知。在这里，作者提出了“ D细胞假说”，该假说解释了NSC功能低下和假定的NSC诱导的D细胞减少，从而导致精神分裂症的中肢边缘DA过度活跃的分子基础。 “ D细胞”被定义为“含非单胺基芳香族L-氨基酸脱羧酶（AADC）的细胞”。 D细胞产生痕量胺，还吸收胺前体，并通过脱羧作用将其转化为胺。作者报告了“人类纹状体特异性的多巴脱羧神经元”，即人纹状体中的“ D-神经元”，以及精神分裂症患者纹状体D-神经元的减少。痕量胺相关受体1型（TAAR1）是痕量胺受体的亚型，具有相当多的配体，例如酪胺，β-苯乙胺（PEA）和甲基苯丙胺，对单胺神经元具有调节功能。已知配体与中脑腹侧被盖区（VTA）的DA神经元的DA末端上的TAAR1受体的结合减少，增加了VTA DA神经元的放电频率。在精神分裂症的大脑中，侧脑室下室区的NSC功能低下可能会导致纹状体和伏隔核中D神经元的减少，并可能导致痕量胺信号的减少。 VTA DA神经元上到达TAAR1的痕量胺信号的减少可能会增加VTA DA神经元的放电频率，并最终导致中脑边缘DA过度活跃。对NSC的DA D2受体刺激的增加可能会抑制NSC的增殖，并可能导致其他中脑边缘DA过度活跃以及D细胞减少。这种新的理论“ D细胞假说”可能解释了精神分裂症发病机理中的中脑边缘DA过度活跃。

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