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首页> 外文期刊>Journal of Behavioral and Brain Science >D-Cell Hypothesis: Pathogenesis of Mesolimbic Dopamine Hyperactivity of Schizophrenia
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D-Cell Hypothesis: Pathogenesis of Mesolimbic Dopamine Hyperactivity of Schizophrenia

机译：D细胞假说：精神分裂症的中脑边缘多巴胺亢进的发病机理

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In the present article, the author proposes a new “D-cell hypothesis” for mesolimbic dopamine (DA) hyperactivity of schizophrenia, of which relevant molecular mechanism has not yet been known. The “D-cell” is defined as “the non-monoaminergic aromatic L-amino acid decarboxylase (AADC)-containing cell”. The D-cell contains AADC but not dopaminergic nor serotonergic. 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 preliminarily the number reduction of D-neurons in the striatum and nucleus accumbens of postmortem brains of patients with schizophrenia. Trace amine-associated receptor, type 1 (TAAR1), a subtype of trace amine receptors, having a large number of ligands, including tyramine, β-phenylethylamine (PEA), and methamphetamine, is a target receptor for the latest neuroleptic discovery. Recent studies have shown that the decreased stimulation of TAAR1 on cell membranes or nerve terminals of DA neurons in the midbrain ventral tegmental area (VTA) increased firing frequency of VTA DA neurons. In brains of schizophrenia, dysfunction of neural stem cells in the subventricular zone of lateral ventricle may cause reduction of the number of D-neurons in the striatum and nucleus accumbens, and may result in decrease of trace amine synthesis. The decrease of stimulation of TAAR1 on terminals of VTA DA neurons caused by trace amine reduction may increase firing frequency of VTA DA neurons, and may finally cause mesolimbic DA hyperactivity. This innovative theory, “D-cell hypothesis” might explain mesolimbic DA hyperactivity in pathogenesis of schizophrenia.
机译：在本文中，作者提出了针对精神分裂症的中脑边缘多巴胺（DA）过度活跃的新“ D细胞假说”，其相关的分子机制尚不清楚。 “ 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细胞含有AADC，但不含多巴胺能或血清素能。 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“人类纹状体特异的多巴脱羧神经元”，即人纹状体中的“ D-神经元”，并初步报道了精神分裂症患者的死后纹状体和伏隔核中D-神经元的数量减少。 。痕量胺相关受体1型（TAAR1）是痕量胺受体的一种亚型，具有大量的配体，包括酪胺，β-苯乙胺（PEA）和甲基苯丙胺，是最新抗精神病药发现的目标受体。最近的研究表明，TAAR1对中脑腹侧被盖区（VTA）的DA神经元的细胞膜或神经末梢的刺激减少，从而增加了VTA DA神经元的放电频率。在精神分裂症的大脑中，侧脑室下室下神经干细胞功能障碍可能导致纹状体和伏隔核中D-神经元数量减少，并可能导致痕量胺合成减少。微量胺还原引起的VTA DA神经元末端TAAR1刺激的减少可能会增加VTA DA神经元的放电频率，并最终导致中脑边缘DA过度活跃。这一创新理论“ 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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