{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T01:58:51Z","timestamp":1770515931193,"version":"3.49.0"},"reference-count":38,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["20-14-00325"],"award-info":[{"award-number":["20-14-00325"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We have recently shown that the periventricular nucleus (PeVN) of adult rats is a \u201cmixed dopaminergic (DAergic) center\u201d containing three thousand neurons: DAergic neurons and those expressing one of the dopamine (DA)-synthesizing enzymes. This study aims to evaluate the development of the PeVN as a mixed DAergic center in rats in the perinatal period, critical for brain morphogenesis. During this period, the PeVN contains DAergic neurons and monoenzymatic neurons expressing individual enzymes of DA synthesis: tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC). In the perinatal period, the total number of such neurons triples, mainly due to monoenzymatic neurons; the content of L-DOPA, the end product of monoenzymatic TH neurons, doubles; and the content of DA, the end product of monoenzymatic AADC neurons and DAergic neurons, increases sixfold. Confocal microscopy has shown that, in the PeVN, all types of neurons and their processes are in close relationships, which suggests their mutual regulation by L-DOPA and DA. In addition, monoenzymatic and DAergic fibers are close to the third cerebral ventricle, located in the subependymal zone, between ependymal cells and in the supraependymal zone. These observations suggest that these fibers deliver L-DOPA and DA to the cerebrospinal fluid, participating in the neuroendocrine regulation of the brain.<\/jats:p>","DOI":"10.3390\/ijms232314682","type":"journal-article","created":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T02:05:37Z","timestamp":1669341937000},"page":"14682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Development of the Periventricular Nucleus as a Brain Center, Containing Dopaminergic Neurons and Neurons Expressing Individual Enzymes of Dopamine Synthesis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8582-8346","authenticated-orcid":false,"given":"Tatiana","family":"Pronina","sequence":"first","affiliation":[{"name":"Laboratory of Neural and Neuroendocrine Regulations, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Pavlova","sequence":"additional","affiliation":[{"name":"Laboratory of Neural and Neuroendocrine Regulations, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliya","family":"Dil\u2019mukhametova","sequence":"additional","affiliation":[{"name":"Laboratory of Neural and Neuroendocrine Regulations, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Ugrumov","sequence":"additional","affiliation":[{"name":"Laboratory of Neural and Neuroendocrine Regulations, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.neurol.2018.07.002","article-title":"Monoamine neurotransmitters and movement disorders in children and adults","volume":"174","author":"Doummar","year":"2018","journal-title":"Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/S1474-4422(11)70141-7","article-title":"The monoamine neurotransmitter disorders: An expanding range of neurological syndromes","volume":"10","author":"Kurian","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/B978-0-12-411512-5.00004-X","article-title":"Brain Neurons Partly Expressing Dopaminergic Phenotype: Location, Development, Functional Significance, and Regulation","volume":"68","author":"Ugrumov","year":"2013","journal-title":"Adv. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/cne.902270403","article-title":"Distribution of tyrosine-hydroxylase-immunoreactive neurons in the hypothalamus of rats","volume":"227","author":"Goldstein","year":"1984","journal-title":"J. Comp. Neurol."},{"key":"ref_5","first-page":"427","article-title":"Immunohistochemical Studies on the Localization and Distribution of Monoamine Neuron Systems in the Rat Brain. I. Tyrosine Hydroxylase in the Mes- and Diencephalon","volume":"54","author":"Johansson","year":"1976","journal-title":"Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1002\/cne.902620410","article-title":"Localization of tyrosine hydroxylase immunoreactive neurons in the cat hypothalamus, with special reference to fluorescence histochemistry","volume":"262","author":"Kitahama","year":"1987","journal-title":"J. Comp. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"472\u2013487.e20","DOI":"10.1016\/j.cell.2018.07.043","article-title":"Anatomically Defined and Functionally Distinct Dorsal Raphe Serotonin Sub-systems","volume":"175","author":"Ren","year":"2018","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/978-1-4684-3860-4_1","article-title":"Localization of Serotonin-Like Immunoreactivity in the Central Nervous System and Pituitary of the Rat, with Special References to the Innervation of the Hypothalamus","volume":"133","author":"Steinbusch","year":"1981","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"108596","DOI":"10.1016\/j.jneumeth.2020.108596","article-title":"Three-dimensional mapping of tyrosine hydroxylase in the transparent brain and adrenal of prenatal and pre-weaning mice: Comprehensive methodological flowchart and quantitative aspects of 3D mapping","volume":"335","author":"Godefroy","year":"2020","journal-title":"J. Neurosci. Methods"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s10571-006-9053-9","article-title":"Three Types of Tyrosine Hydroxylase-Positive CNS Neurons Distinguished by Dopa Decarboxylase and VMAT2 Co-Expression","volume":"26","author":"Weihe","year":"2006","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ugrumov, M.V., Pavlova, E.N., Kolacheva, A.A., Dil\u2019Mukhametova, L.K., Bogdanov, V.V., Blokhin, V., and Pronina, T.S. (2022). The Periventricular Nucleus as a Brain Center Containing Dopaminergic Neurons and Neurons Expressing Individual Enzymes of Dopamine Synthesis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126739"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.brainres.2011.01.101","article-title":"Increasing proportions of tyrosine hydroxylase-immunoreactive interneurons colocalize with choline acetyltransferase or vasoactive intestinal peptide in the developing rat cerebral cortex","volume":"1383","author":"Asmus","year":"2011","journal-title":"Brain Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0304-3940(99)00409-7","article-title":"Tyrosine hydroxylase and aromatic l-amino acid decarboxylase do not coexist in neurons in the human anterior cingulate cortex","volume":"269","author":"Ikemoto","year":"1999","journal-title":"Neurosci. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1267\/ahc.06019","article-title":"Tyrosine Hydroxylase (TH)- and Aromatic-L-Amino Acid Decarboxylase (AADC)-Immunoreactive Neurons of the Common Marmoset (Callithrix jacchus) Brain: An Immunohistochemical Analysis","volume":"40","author":"Karasawa","year":"2007","journal-title":"Acta Histochem. Cytochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0891-0618(98)00060-X","article-title":"Aromatic l-amino acid decarboxylase- and tyrosine hydroxylase-immunohistochemistry in the adult human hypothalamus","volume":"16","author":"Kitahama","year":"1998","journal-title":"J. Chem. Neuroanat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/S0306-4522(00)00154-8","article-title":"Striatal cells containing aromatic l-amino acid decarboxylase: An immunohistochemical comparison with other classes of striatal neurons","volume":"98","author":"Mura","year":"2000","journal-title":"Neuroscience"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0891-0618(97)10019-9","article-title":"Tyrosine hydroxylase- and\/or aromatic l-amino acid decarboxylase-containing cells in the suprachiasmatic nucleus of the Syrian hamster (Mesocricetus auratus)","volume":"14","author":"Novak","year":"1998","journal-title":"J. Chem. Neuroanat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jchemneu.2009.06.010","article-title":"Aromatic l-amino acid decarboxylase-immunoreactive structures in human midbrain, pons, and medulla","volume":"38","author":"Kitahama","year":"2009","journal-title":"J. Chem. Neuroanat."},{"key":"ref_19","first-page":"59","article-title":"Do Tyrosine Hydroxylase-Immunoreactive Neurons in the Ventrolateral Arcuate Nucleus Produce Dopamine or Only L-Dopa?","volume":"1","author":"Meister","year":"1988","journal-title":"J. Chem. Neuroanat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.neuroscience.2014.06.051","article-title":"Neurons expressing individual enzymes of dopamine synthesis in the mediobasal hypothalamus of adult rats: Functional significance and topographic interrelations","volume":"277","author":"Ugrumov","year":"2014","journal-title":"Neuroscience"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jchemneu.2005.04.001","article-title":"Degeneration of dopaminergic neurons triggers an expression of individual enzymes of dopamine synthesis in non-dopaminergic neurons of the arcuate nucleus in adult rats","volume":"30","author":"Ershov","year":"2005","journal-title":"J. Chem. Neuroanat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.nbd.2016.12.005","article-title":"Cooperative synthesis of dopamine by non-dopaminergic neurons as a compensatory mechanism in the striatum of mice with MPTP-induced Parkinsonism","volume":"98","author":"Kozina","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1210\/edrv.22.6.0451","article-title":"Dopamine as a Prolactin (PRL) Inhibitor","volume":"22","author":"Hnasko","year":"2001","journal-title":"Endocr. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lopez, V.M., Decatur, C.L., Stamer, W.D., Lynch, R.M., and McKay, B.S. (2008). L-DOPA Is an Endogenous Ligand for OA1. PLoS Biol., 6.","DOI":"10.1371\/journal.pbio.0060236"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Speranza, L., di Porzio, U., Viggiano, D., de Donato, A., and Volpicelli, F. (2021). Dopamine: The Neuromodulator of Long-Term Synaptic Plasticity, Reward and Movement Control. Cells, 10.","DOI":"10.3390\/cells10040735"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/cne.10173","article-title":"Differentiation of tyrosine hydroxylase-synthesizing and\/or aromaticL-amino acid decarboxylase-synthesizing neurons in the rat mediobasal hypothalamus: Quantitative double-immunofluorescence study","volume":"446","author":"Ershov","year":"2002","journal-title":"J. Comp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.neuroscience.2004.01.002","article-title":"Dopamine synthesis by non-dopaminergic neurons expressing individual complementary enzymes of the dopamine synthetic pathway in the arcuate nucleus of fetal rats","volume":"124","author":"Ugrumov","year":"2004","journal-title":"Neuroscience"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jchemneu.2009.08.004","article-title":"Non-dopaminergic neurons partly expressing dopaminergic phenotype: Distribution in the brain, development and functional significance","volume":"38","author":"Ugrumov","year":"2009","journal-title":"J. Chem. Neuroanat."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/BF02152056","article-title":"From oocyte to neuron: Do neurotransmitters function in the same way throughout development?","volume":"16","author":"Buznikov","year":"1996","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0166-2236(93)90162-F","article-title":"Neurotransmitters as growth regulatory signals: Role of receptors and second messengers","volume":"16","author":"Lauder","year":"1993","journal-title":"Trends Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s11064-010-0127-1","article-title":"Developing Brain as an Endocrine Organ: A Paradoxical Reality","volume":"35","author":"Ugrumov","year":"2010","journal-title":"Neurochem. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1530\/eje.0.1390337","article-title":"Prolactin secretion and its dopamine inhibitory control in rat fetuses","volume":"139","author":"Melnikova","year":"1998","journal-title":"Eur. J. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-1-4614-6199-9_3","article-title":"Neuroanatomy of the Kisspeptin Signaling System in Mammals: Comparative and Developmental Aspects","volume":"784","author":"Lehman","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"0150\u201317","DOI":"10.1523\/ENEURO.0150-17.2017","article-title":"Effects of Selective Deletion of Tyrosine Hydroxylase from Kisspeptin Cells on Puberty and Reproduction in Male and Female Mice","volume":"4","author":"Stephens","year":"2017","journal-title":"eNeuro"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"89","DOI":"10.32607\/actanaturae.11516","article-title":"A Comparative Analysis of CSF and the Blood Levels of Monoamines as Neurohormones in Rats during Ontogenesis","volume":"13","author":"Murtazina","year":"2021","journal-title":"Acta Naturae"},{"key":"ref_36","unstructured":"Ashwell, K.W.S., and Paxinos, G. (2008). Atlas of the Developing Rat Nervous System, COMPACT, Academic Press. [3rd ed.]."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0005-2736(01)00384-4","article-title":"Human L-type amino acid transporter 1 (LAT1): Characterization of function and expression in tumor cell lines","volume":"1514","author":"Yanagida","year":"2001","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/ar.1090940210","article-title":"Estimation of nuclear population from microtome sections","volume":"94","author":"Abercrombie","year":"1946","journal-title":"Anat. Rec."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14682\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:26:03Z","timestamp":1760145963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":38,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232314682"],"URL":"https:\/\/doi.org\/10.3390\/ijms232314682","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,24]]}}}