Neural and Neuroendocrine Regulations

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About the Lab

Please check topical info about the Lab of Neural and Neuendocrine Regulations on the website (https://www.neuroreg.org/).

Research Areas 

1. Cellular and molecular mechanisms of neurotransmission, neurodegeneration, and neuroplasticity

Introduction. The functioning of the brain is provided by the labile neural networks, where information is transferred from neuron to neuron due to volume and synaptic neurotransmission. In ontogenesis, from embryogenesis to aging, the functioning of the brain is associated with the death of neurons (neurodegeneration) and initiation of compensatory processes (neuroplasticity). In pathology, the rate of neurodegeneration increases, which leads first to stimulation and then to depletion of the compensatory reserve of the brain.

Objective. The objective of this research area is to examine the cellular and molecular mechanisms of neurotransmission, neurodegeneration, and neuroplasticity.

Main achievements. We have discovered a new pathway for the synthesis of classical neurotransmitters. In fact, it was shown that: (i) dopamine is synthesized as an end product not only in dopaminergic neurons, but also in non-dopaminergic neurons containing one of the complementary enzymes of dopamine synthesis, tyrosine hydroxylase or aromatic L-amino acid decarboxylase; (ii) dopamine is produced by non-dopaminergic monoenzymatic neurons in a number of brain regions during the entire ontogenesis; (iii) cooperative synthesis of dopamine by non-dopaminergic neurons is an important mechanism of neuroplasticity whenever there is a failure of dopaminergic neurons, for example, in hyperprolactinemia and Parkinson's disease.

Selected publications: 
  • Ugrumov MV. Non-dopaminergic neurons partly expressing dopaminergic phenotype: distribution in the brain, development and functional significance. J Chem Neuroanat. 2009;38(4):241-256. doi:10.1016/j.jchemneu.2009.08.004
  • Ugrumov MV. Brain neurons partly expressing dopaminergic phenotype: location, development, functional significance, and regulation. Adv Pharmacol. 2013;68:37-91. doi:10.1016/B978-0-12-411512-5.00004-X
  • M Ugrumov, J Taxi, T Pronina, A Kurina, A Sorokin, A Sapronova, A Calas. Neurons expressing individual enzymes of dopamine synthesis in the mediobasal hypothalamus of adult rats: functional significance and topographic interrelations. Neuroscience. 2014;277:45-54. doi:10.1016/j.neuroscience.2014.06.051
  • Kozina EA, Kim AR, Kurina AY, Ugrumov MV. Cooperative synthesis of dopamine by non-dopaminergic neurons as a compensatory mechanism in the striatum of mice with MPTP-induced Parkinsonism. Neurobiol Dis. 2017;98:108-121. doi:10.1016/j.nbd.2016.12.005

2. The neuroendocrine system and its role in the body 

Introduction. The neuroendocrine system regulates the most important functions, including the development of the whole organism, reproduction, and the maintenance of homeostasis. This is a sophisticated hierarchical four-level system based on a cybernetic principle: all the levels are interconnected in accordance with direct regulation and feedback regulation. Functional levels are represented by the central nervous system, including the "endocrine" hypothalamus, adenohypophysis, peripheral endocrine glands, and peripheral target organs. Disruption of the neuroendocrine system leads to the development of congenital diseases, impaired reproduction and adaptation to the environment, as well as various metabolic diseases.

Objective. The main objective of this research area is to study the development of the neuroendocrine system in ontogenesis with an emphasis on the role of the brain in regulating the development and functioning of the whole organism.

Main achievements. We have hypothesized and proved that the developing brain operates as an endocrine organ during the period from the neuron origin in embryogenesis until the maturation of neuronal synaptic networks and the blood brain barrier. Indeed, during this period, the developing brain secretes physiologically active substances into the general circulation, providing direct (neuro)endocrine control over the development of peripheral target organs and the brain itself. In turn, an impairment of this regulation leads to the development of congenital diseases.

Selected publications:
  • Ugrumov MV. Developing brain as an endocrine organ: a paradoxical reality. Neurochem Res. 2010;35(6):837-850. doi:10.1007/s11064-010-0127-1
  • Ugrumov MV, Saifetyarova JY, Lavrentieva AV, Sapronova AY. Developing brain as an endocrine organ: secretion of dopamine. Mol Cell Endocrinol. 2012;348(1):78-86. doi:10.1016/j.mce.2011.07.038
  • Yulia Z, Diana N, Anna S, Michael U. Brain as an endocrine source of circulating 5-hydroxytryptamine in ontogenesis in rats. Mol Cell Endocrinol. 2014;393(1-2):92-98. doi:10.1016/j.mce.2014.06.006
  • Murtazina AR, Nikishina YO, Bondarenko NS, Dil'mukhametova LK, Sapronova AY, Ugrumov MV. Developing brain as a source of circulating norepinephrine in rats during the critical period of morphogenesis. Brain Struct Funct. 2019;224(9):3059-3073. doi:10.1007/s00429-019-01950-5

3. Neurodegenerative diseases

Introduction. One of the global challenges of the 21st century is the fight against socially significant neurodegenerative diseases, primarily Alzheimer's and Parkinson's. These diseases are diagnosed 20-30 years after the onset upon the appearance of characteristic clinical symptoms. By this time, most of the specific neurons have degenerated, which explains the limited efficacy of the current treatment options which fail to prevent disability and death.

Objective. The objective of this research area is to study the cellular and molecular mechanisms of the pathogenesis of Parkinson's disease at an early (preclinical) stage and, based on these data, to develop preclinical diagnostic strategies and preventive neuroprotective treatment. This would extend the preclinical stage, the period of normal physical and social activity of the patient.

Main achievements. 

  1. Original neurotoxic models in vitro and in vivo of the stagewise progression of Parkinson's disease have been developed and thoroughly characterized. 
  2. Current methodology for the development of early diagnosis of Parkinson's disease by searching for markers in the blood of untreated patients at an early clinical stage has been improved by verifying these markers in animal neurotoxic models.
  3. We have proposed for the first time in neurology and psychiatry to use provocative tests for early (preclinical) diagnosis of chronic brain diseases, including neurodegenerative diseases. A provocative test for the diagnosis of Parkinson's disease has been developed in animal models using a reversible, non-metabolizable inhibitor of dopamine synthesis.
Selected publications:
  • Ugrumov MV, Khaindrava VG, Kozina EA, Kucheryanu VG, Bocharov EV, Kryzhanovsky GN, Kudrin VS, Narkevich VB, Klodt PM, Rayevsky KS, Pronina TS. Modeling of presymptomatic and symptomatic stages of parkinsonism in mice. Neuroscience. 2011;181:175-188. doi:10.1016/j.neuroscience.2011.03.007
  • Khakimova GR, Kozina EA, Kucheryanu VG, Ugrumov MV. Reversible pharmacological induction of motor symptoms in MPTP-treated mice at the presymptomatic stage of Parkinsonism: potential use for early diagnosis of Parkinson's disease. Mol Neurobiol. 2017;54(5):3618-3632. doi:10.1007/s12035-016-9936-9
  • Mingazov ER, Khakimova GR, Kozina EA, Medvedev AE, Buneeva OA, Bazyan AS, Ugrumov MV. MPTP mouse model of preclinical and clinical Parkinson's disease as an instrument for translational medicine. Mol Neurobiol. 2018;55(4):2991-3006. doi:10.1007/s12035-017-0559-6
  • Kim A, Nigmatullina R, Zalyalova Z, Soshnikova N, Krasnov A, Vorobyeva N, Georgieva S, Kudrin V, Narkevich V, Ugrumo M. Upgraded methodology for the development of early diagnosis of Parkinson's disease based on searching blood markers in patients and experimental models. Mol Neurobiol. 2019;56(5):3437-3450. doi:10.1007/s12035-018-1315-2
  • Ugrumov M. Development of early diagnosis of Parkinson's disease: Illusion or reality? [published online ahead of print, 2020 Jun 29]. CNS Neurosci Ther. 2020;10.1111/cns.13429. doi:10.1111/cns.13429