Activities – study of the neurobiological foundations of the formation of addictions, addictive memory and chronic opiate addiction, search for opportunities to influence the development and consolidation of addictive memory, its fading and reconsolidation.

Research methods – study of animal behavior (conditioned reflex preference for place, open field, elevated plus maze, hot plate, etc.); morphological and immunohistochemical methods, introduction of neurotracers; cultural - mouse neuroblastoma culture С-1300, organotypic culture of the hippocampus; electrophysiological - models of synaptic plasticity on surviving sections and organotypic cultures of the hippocampus, patch-Clamp.

The main direction of the work of the laboratory is the study of the interaction of the immune and nervous systems in the norm and in the development of drug addiction.. In recent years, work has focused on studying the action of bone marrow regulatory peptides. (myelopeptide). Interest in the study of myelopeptides was due to the fact, what we found, that the drug based on them (Myelopid), and as it turned out later, and individual myelopeptides, significantly increased the time, necessary for the development of dependence on morphine in animals. In experiments on the culture of neuroblastoma C-1300, it was shown, that myelopeptides are able to induce morphological and functional differentiation of neuroblasts and have a protective effect during morphine intoxication and deprivation of oxygen and glucose. Under morphine-induced oxidative stress, myelopeptides reduced the content of active oxidative radicals in neuroblastoma cells and the total number of cells with signs of apoptosis..

The neuroprotective properties of myelopeptides were also revealed in the organotypic culture of the hippocampus during the toxic effect of morphine.. All myelopeptides slowed the development of tolerance to the analgesic action of morphine., the data obtained can serve as the basis for an extended pharmacological preclinical study with the possible subsequent creation of a drug for use in clinical practice. The difference between them was revealed when studying their influence on the formation of addictive memory on the model of morphine-induced conditioned reflex place preference. (URPM).

Comparing these results with our data on the effect of myelopeptides on the synaptic plasticity of the hippocampus, we found a correlation. So, myelopeptides, inhibiting the formation of long-term post-tetanic potentiation, blocked the expression of URPM, and myelopeptide, facilitating potentiation, did not interfere with expression and inhibited the extinction of addictive memory. These data are of interest for further study of the possibility of their application in experiments on blocking the formation and reconsolidation of addictive memory and enhancing its extinction.. Mechanisms of action of myelopeptides, Unfortunately, remain unknown. One of such mechanisms in the central nervous system may be the effect of myelopeptides on the state of microglial cells..

Chronic dependence on opiates leads to the development of the so-called sterile neuroinflammation., what is recorded by the change in astro activity- and microglial cells and increased production of pro-inflammatory cytokines and chemokines. We have studied the state of microglia in four parts of the brain in mice with experimental chronic dependence on morphine (hippocampus and dentate fascia, nucleus accumbens, ventral tegmental area, periaqueductal gray matter).

Activation of microglia according to the pro-inflammatory M1 type was found in all structures in dependent animals.. The introduction of myelopeptides during the development of addiction in animals reduced the number of microglial cells M1-type. In normal animals, myelopeptides did not cause pro-inflammatory activation of microglia.. Mice addicted to morphine showed a decrease in the number of microglial cells, activated by anti-inflammatory type ("recovery" or M2-type). Individual myelopeptides contributed to an increase in the number of M2-activated microgliocytes in chronically dependent animals. In general, the data obtained confirm, that myelopeptides are regulators of the functional activity of microglia, and act as messenger molecules, mediating interactions between the immune and nervous systems

Publications

Laboratory staff

1. Beregovoy Nikolai Alekseevich, Leading Researcher, candidate of biological sciences
   ber@niimbb.ru, n_bergg@mail.ru
   +7 (383) 333-54-72
2. Pankova Tatyana Mikhailovna, research laboratory assistant, candidate of biological sciences
   pan@niimbb.ru
   +7 (383) 333-54-72
3. Sorokina Nina Sergeevna, Researcher
   nina@niimbb.ru
   +7 (383) 333-54-72
4. Volcho Gleb Konstantinovich, junior researcher
   gleb.volcho@mail.ru
   +7 (383) 333-54-72
5. Tarasova Anna Evgenievna, research laboratory assistant
   ann@teworks.com
   +7 (383) 333-54-72
6. Devederkina Tamara Ivanovna, laboratory assistant
   +7 (383) 333-54-72