The Periventricular Nucleus as a Brain Center Containing Dopaminergic Neurons and Neurons Expressing Individual Enzymes of Dopamine Synthesis

Abstract

Since the 1980s, the concept of dopamine-rich brain centers as clusters of only dopaminergic neurons has been fundamentally revised. It has been shown that, in addition to dopaminergic neurons, most of these centers contain neurons expressing one of the enzymes of dopamine synthesis: tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC). We have obtained convincing evidence that in rats, the hypothalamic periventricular nucleus (PeVN) is one of the largest dopamine-rich centers, containing dopaminergic and monoenzymatic neurons. Indeed, using double immunostaining for TH and AADC, the PeVN was shown to contain almost three thousand dopaminergic and monoenzymatic neurons. According to high-performance liquid chromatography, PeVN contains L-DOPA and dopamine, which, apparently, are synthesized in monoenzymatic TH neurons and bienzymatic neurons, respectively. According to confocal microscopy, neurons (cell bodies, fibers), which were immunopositive only to TH, only to AADC, or both, are in close topographic relationships with each other and with the 3rd ventricle. These data suggest the mutual regulation of the neurons, as well as the delivery of dopamine and L-DOPA to the third ventricle, which is confirmed by their detection in the cerebrospinal fluid. Thus, evidence has been obtained that PeVN is one of the largest dopamine-rich centers of the brain, containing dopaminergic and monoenzymatic neurons.

Striatal Neurons Partially Expressing a Dopaminergic Phenotype: Functional Significance and Regulation

“…Previous studies have emphasized that L-DOPA, as the final secretory product in monoenzymatic TH neurons, can play the role of a modulator of DA and norepinephrine receptors, as well as a neurotransmitter affecting specific receptors [ 39 , 40 ]. It is also suggested that L-DOPA controls the development of the brain as a morphogenetic factor [ 12 , 41 ]. Our knowledge of the functional role of L-DOPA can be expanded if taking into account our confocal microscopic observations of GFP-stained monoenzymatic TH-immunopositive nerve fibers located in the periventricular zone of the striatum and between ependymal cells of lateral ventricles.…”

“…Our knowledge of the functional role of L-DOPA can be expanded if taking into account our confocal microscopic observations of GFP-stained monoenzymatic TH-immunopositive nerve fibers located in the periventricular zone of the striatum and between ependymal cells of lateral ventricles. These data suggest that striatal monoenzymatic TH nerve fibers are one of the sources of L-DOPA contained in the cerebrospinal fluid [ 41 ].…”

“…For immunohistochemical studies, the brains of some transgenic mice ( n = 4) were isolated and frozen according to the previously described method [ 36 , 41 ]. Other transgenic mice ( n = 25) were decapitated under anesthesia with 2.4% isoflurane (Baxter, Deerfield, IL, USA), and the brain was removed.…”

Development of the Periventricular Nucleus as a Brain Center, Containing Dopaminergic Neurons and Neurons Expressing Individual Enzymes of Dopamine Synthesis

“…Indeed, when using double immunolabeling for TH and aromatic L-amino acid decarboxylase (AADC), the second enzyme of DA synthesis, it has been shown that some DAergic centers, for example, the compact part of the substantia nigra, contain practically only DAergic (bienzymatic) neurons, whereas in other DAergic centers, along with DAergic neurons, there are neurons expressing only one of the DA-synthesizing enzymes, TH or AADC [ 3 , 10 ]. Such “mixed” DAergic centers include: the arcuate nucleus (AN), the striatum, the periventricular nucleus (PeVN), and a number of other smaller centers [ 3 , 11 ].…”

“…Studies following the discovery of neurons containing one of the DA-synthesizing enzymes have shown that: (i) the number of monoenzymatic neurons in the brain exceeds the number of DAergic neurons [ 3 , 12 , 13 , 14 , 15 , 16 , 17 ]; (ii) the end secretory product of neurons expressing only TH is L-3,4-dihydroxyphenylalanine (L-DOPA), and the end product of neurons expressing only AADC, or TH and AADC, is DA [ 18 , 19 , 20 ]; (iii) neurons expressing only TH and only AADC synthesize DA in cooperation [ 20 ]; (iv) cooperative synthesis of DA by monoenzymatic neurons is considered as a compensatory response to a failure of DAergic neurons and the resulting DA deficiency, e.g., due to neurodegeneration [ 21 , 22 ]; and (v) L-DOPA and DA synthesized by monoenzymatic neurons play the role of neurotransmitters in the nervous tissue or that of a neurohormone when delivered into the cerebrospinal fluid or blood [ 11 , 23 , 24 , 25 ]. The above data were obtained mainly from the study of the AN, which was identified already in the early 2000s as a mixed DAergic center [ 26 , 27 ].…”