D-Cell Hypothesis: Pathogenesis of Mesolimbic Dopamine Hyperactivity of Schizophrenia

作     者：Keiko Ikemoto 

作者机构：Department of Neuropsychiatry Fukushima Medical University School of Medicine Fukushima Japan 

出 版 物：《Journal of Behavioral and Brain Science》 (行为与脑科学期刊（英文）)

年 卷 期：2012年第2卷第3期

页      面：411-414页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Dopamine D-Neuron Ventral Tegmental Area Schizophrenia TAAR1 

摘      要：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.