Why D-neuron? Importance in schizophrenia research

作     者：Keiko Ikemoto 

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

出 版 物：《Open Journal of Psychiatry》 (精神病学期刊（英文）)

年 卷 期：2012年第2卷第4期

页      面：393-398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 Aromatic L-Amino Acid Decar-boxylase 

摘      要：Recent pharmacological discovery on trace amine-associated receptor, type 1(TAAR1) has emphasized importance of trace amines in pathogenesis of psychoses, such as schizophrenia. TAAR1 has many ligands, including tyramine, β-phenylethylamine (PEA), amphetamines, and 3’-iodothyronamine. So-called D-neurons are putative producer of trace amines, endogenous ligands of TAAR1. The D-neuron is defined “the aromatic L-amino acid decarboxylase (AADC)-containing neuron, but not dopaminergic nor serotonergic, i.e. not containing tyrosine hydroxylase nor tryptophan hydroxylase. AADC is an enzyme, also called dopa decarboxylase (DDC). The localization of D-neurons in the central nervous system has been specified into 15 groups, from the spinal cord (D1) to striatum (D15). We showed the decrease of D-neurons in D15 in postmortem brains of schizophrenia, where midbrain dopamine (DA) neurons are heavily innervated. Decrease of D-neurons may cause reduction of trace amines in the striatum, and may also decrease stimulation of TAAR1 on striatal terminals of ventral tegmental area (VTA) DA neurons. This might increase firing frequency of VTA DA neurons, and causes DA hyperactivity in the striatum and nucleus accumbens. In the present article, the author introduces the novel theory, “D-cell hypothesis, for mesolimbic DA hyperactivity of schizophrenia. Some clinical and/or experimental evidences that support this hypothesis are mentioned. The D-neuron, as a trace amine producer, is a clue for elucidating pathogenesis of psychoses, as well as human mental functions. Thus, signal transduction of D-neurons should be investigated.