Dopamine-Producing Neurons in Rat Ontogeny: Phenotypic Features Underlying Molecular Mechanisms of Secretion and Regulation

Russian Journal of Developmental Biology. 2020. Vol. 51. No. 1. P. 57–64.

Kurtova A. I., Dil’mukhametova L. K., Pronina T. S., Mingazov E. R., Ugrumov M.

Dopamine (DA), which is synthesized in DA-ergic neurons and so-called monoenzymatic neurons,
is involved in the regulation of neuronal differentiation during the critical period of morphogenesis. The
aim of the present study was to examine phenotypic features of DA-producing neurons in several brain
regions, including the striatum, suprachiasmatic nucleus, and arcuate nucleus, during rat ontogeny starting
from embryonic day 18 (E18) to postnatal day 60 (P60). The enzymes of DA synthesis tyrosine hydroxylase
(TH) and aromatic amino acid decarboxylase (AAAD), vesicular monoamine transporters (VMAT), and D1
and D2 DA receptors were used as markers for functional activity of DA neurons. Expression of these markers
was studied using double immunohistochemical labeling of TH and AAAD or PCR assay of TH, AAAD,
VMAT1, VMAT2, and D1 and D2 DA receptors. In the striatum, mRNAs of all mentioned markers were
revealed within the whole period of ontogeny studied, bienzymatic TH and AAAD-immunopositive neurons
were observed at E18, whereas monoenzymatic TH- or AAAD-containing neurons were observed at P60 only. In
the suprachiasmatic nucleus, monoenzymatic AAAD neurons coexist with monoenzymatic TH-immunoreactive
fibers, which innervate the ventral part of the nucleus, in the early postnatal period (P10). At P10 in the suprachiasmatic
nucleus, the TH, VMAT1, and VMAT2 genes are not expressed; however, transcripts of the D1
and D2 genes were detected. The arcuate nucleus of rat embryos contained only monoenzymatic TH neurons
in the ventrolateral area and AAAD neurons in the dorsomedial area in the late prenatal period (E21). At the
same time TH, AAAD, VMAT2, D1, and D2 mRNAs were expressed in both parts of the arcuate nucleus.
Thus, during rat ontogeny, nondopaminergic neurons containing one of the enzymes, TH or AAAD, are
present in the striatum, suprachiasmatic nucleus, and arcuate nucleus, which allows for suggesting the cooperative
synthesis of dopamine in these brain structures.

Keywords: brain, Ventral striatum, dopamine, Tyrosine hydroxylase, ontogeny, monoenzymatic neurons, aromatic amino acids decarboxylase, arcuate nucleus, suprachiasmatic nucleus