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

Introduction

The functioning of the brain is provided by the labile neuronal circuits, 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

In this case, L-DOPA secreted by monoenzymatic TH-expressing neurons is captured via the large neutral amino acid transporter type 1 (LAT1) to AADC-expressing neurons for dopamine synthesis;

2) Dopamine is produced by non-dopaminergic monoenzymatic neurons in a number of brain regions during the entire ontogenesis;

3) Cooperative synthesis of dopamine by non-dopaminergic neurons is an important mechanism of neuroplasticity under a failure of dopaminergic neurons, e.g., in hyperprolactinemia and Parkinson's disease;

4) L-DOPA, secreted by monoenzymatic neurons expressing tyrosine hydroxylase, is involved in dopamine synthesis in any cell containing aromatic L-amino acid decarboxylase, e.g., serotoninergic neurons and noradrenergic neurons.

Key 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.

• Ugrumov M , Taxi J, Pronina T , Kurina A, Sorokin A, Sapronova A, Calas A. 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.

II. 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 maintaining of homeostasis. This sophisticated hierarchical four-level system is based on a cybernetic principle - all levels are interconnected via 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 (BBB). 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.

Key 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.

• Zubova Yu., Nasyrova D., Sapronova A., Ugrumov M. 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.