Why D-neuron? Direction from Psychiatric Research

Abstract

Recent pharmacological discovery on Trace Amine-Associated Receptor, type 1 (TAAR1) showed possible involvement of trace amines in pathogenesis of psychoses, such as schizophrenia. TAAR1 has many ligands, including tyramine, beta-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 “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 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 cause DA hyperactivity in the striatum and nucleus accumbens. The novel hypothesis for etiology of mesolimbic DA hyperactivity of schizophrenia was introduced. 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 further be investigated.