Keiko Ikemoto
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.