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Neuroscience research.

Being a Center of biological psychiatry a WHO Collaborating Center has paid great attention to the development of scientific research in the area of neuroscience.

Fundamental studies in the area of neuroscience were carried out in the Center on a large scale. They were in a direct relation to the problems of the modern psychiatry as they were connected with the study of etiology and pathogenesis of mental disorders. Besides the object of such studies was to develop new methods of treatment and to establish the mechanisms of the effect of new drugs on the human brain. Corresponding studies were conducted in all the basic areas of neuroscience - brain genetics, biochemistry, neurochemistry, neuroimmunology, pathophysiology, neuromorphology, etc., including the development of new methods of research, which was part of the concept of high technologies.

All the laboratories of the genetic profile directly participated in deciphering of a human genome (also as participants of international scientific research groups).

A new generation of genetic markers was developed for gene mapping of hereditary diseases, including mental and neurologic disorders.

Mutations, polymorphism, and structure of preseneline genes were characterized, which encode quite a new type of transmembrane proteins responsible for the development of the central nervous system.

A new regulator ("nicastrin") and a complex of proteins ("secretosoma") were discovered, which are responsible for the signal tranduction (Notch) in the early neurogenesis.

A collection of DNA-probes was created for the identification of human chromosomes, molecular and cytogenetic studies, and diagnostics of chromosome diseases and monogenic neurologic and psychiatric syndromes.

New methods of pre- and postnatal diagnostics of various forms of chromosome pathology by means of multicolor fluorescent hybridization of nuclear acids in situ (mFish) were developed. (mFISH) method was approved for studying the human brain also in cases of mental disorders. A strategy adequate for mental disorders with a complex of appropriate mathematical programs was developed for the study of genetically determined biological markers. The ability of agonists of Opioid delta-type receptors (pelargine, in particular) to decrease anxiety was demonstrated in experimental animals. Differences in the state of receptor protein of delta-Opioid brain receptors were detected in animals with various levels of behavioral anxiety manifestations by means of radioreceptor method, molecular and biological methods, and Western-blotting. It was established that a high level of autoantibodies to the factor of nervous growth was a marker of a group of diseases, connected with a disturbance of neuroontogenesis, determining a predilection for their development. This marker makes it possible to single out the corresponding groups of a high risk.

Data was obtained testifying to the fact that the development of autoimmune reactions in cases of pathological states of the nervous system may be initiated by the presence (or activation) on the early stages of ontogeny of viruses, the antigene determinants of which have immunological chiasm with neurotropines.

An ability of home-produced peptide drugs called Semax and Selukk to inhibit the activity of enkephalin-degrading enzymes was demonstrated, which possibly determines one of the mechanisms of their anxiolytic effect. (These drugs were invented under the leadership of N.F. Myasoedov, Academician of Russian Academy of Sciences, the Institute of Molecular Genetics of the Russian Academy of Sciences, and Academician S.B. Seredinin - Scientific Research Pharmacological Institute of the Russian Academy of Medical Sciences).

The following 3 glutamatdehydrogenase isoforms were discovered in a human brain: 2 soluable ones and 1 membrane-bound (in contrast to 2 isoforms, which were found in animals). All 3 isoforms were characterized in accordance with their physical and chemical properties. Antiserums to all 3 isoforms were obtained and quantitative methods of determination were developed, which made it possible to reveal their distribution in a number of human brain structures.

Glutaminesynthetase (GS) and GS-like protein (GSLP) were isolated from the human brain. A method of their separate evaluation was developed and specificities of their distribution in various brain areas were determined in case of schizophrenia as compared to that of the normal brain.

Monoclone antibodies to S-terminal end of polypeptide sequence of serotonine protein-carrier were obtained. On this basis a method of determination of molecular weight and quantitative content of the given protein in human thrombocytes of a man was created (in collaboration with the Laboratory of Clinical Neuroimmunology of the Mental Health Research Center of the Russian Academy of Medical Sciences).

The following new quantitative methods of study of the brain tissue structural components were developed and introduced:

A method of physical disector for the determination of the numerical density of synapses in a unit of tissue volume during electronic microscope studies;

A method of evaluation of numerical density per neuron;

A method of optical disector for photooptical study of numerical density of neurons and glias per unit of tissue volume;

New methods of statistical data processing with an introduction of multifactor analysis were demonstrated.