INDICATORS OF FUNCTIONAL ACTIVITY OF NERVOUS AND IMMUNE SYSTEMS IN MICE WITH MUTATIONS IN THE DISC1 GENE

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Abstract

Schizophrenia is a multifactorial disease, the pathogenesis of which against the background of immune dysfunction consists of a complex interaction of the genetic characteristics of the organism and environmental factors. To better match the available experimental model of schizophrenia (mouse DISC1- L100P) to the genetic diversity of psychopathology that is observed in humans, we have obtained and studied animals that combine two diff erent mutant alleles of the DISC1 gene (Disrupted-in-Schizophrenia-1). The purpose of this work was to study emotional, social and cognitive behavior in mice carrying two mutations in the DISC1 gene – L100P and Q31L and their comparison to the spectrum of pro- and anti-infl ammatory cytokines in the brain structures of DISC1-L100P mice. Males DISC1-L100P/Q31L mice, in contrast to females, showed a more pronounced defi cit of prepulse inhibition to the 72 dB signal. All studied groups showed the absence of a depressive-like behavior in the tail suspention test. Since DISC1-L100P mice are characterized by changes in the cytokine profi le in the brain structures involved in the pathogenetic mechanisms of schizophrenia, the experimental model of DISC1-L100P/Q31L mice seems promising in studying the contribution of epigenetic eff ects, including maternal immune activation, to schizophrenia pathogenesis.

About the authors

N. D. Chizhova

Federal State Budgetary Educational Institution of Higher Education «Novosibirsk State University»

Author for correspondence.
Email: chnadezhda1995@gmail.com

Undergraduate,

Novosibirsk

Russian Federation

T. V. Lipina

Federal State Budgetary Scientific Institution «Scientifi c Research Institute of Physiology and Basic Medicine»

Email: fake@neicon.ru

Doctor of Biological Sciences, Head of the Laboratory of experimental models of the pathology of cognition and emotions, Chief Researcher,

Novosibirsk

Russian Federation

T. G. Amstislavskaya

Federal State Budgetary Educational Institution of Higher Education «Novosibirsk State University»;
Federal State Budgetary Scientific Institution «Scientifi c Research Institute of Physiology and Basic Medicine»

Email: fake@neicon.ru

Doctor of Biological Sciences, Head of the Translational Biopsychiatry Laboratory, Chief Researcher,

Novosibirsk

Russian Federation

References

  1. Lipina T. V., Roder J. C. Disrupted-In-Schizophrenia-1 (DISC1) interactome and mental disorders: Impact of mouse models. Neurosci. Biobehav. Rev. 2014, 45, 271–294.
  2. Геворгян М. М., Жанаева С. Я., Альперина Е. Л., Идова Г. В., Липина Т. В. Спектр цитокинов в структурах головного мозга мышей Disc-1-L100P c шизофреноподобным поведением. Нейроиммунология. 2017, 14 (1–2), 23–24
  3. Lipina T. V., Zai C., Hlousek D., Roder J. C., Wong A. H. Maternal Immune Activation during Gestation Interacts with Disc1 Point Mutation to Exacerbate Schizophrenia-Related Behaviors in Mice. The Journal of Neuroscience. 2013, 33 (18), 7654–7666.
  4. Patterson P. H. Immune involvement in schizophrenia and autism: etiology, pathology, and animal models. Behav. Brain Res. 2009, 204, 313–321. 5. Markova E. V., Obukhova L. A., Kolosova N. G. Parameters of cell immune response in Wistar and OXYS rats and their behavior in the open fi eld test. Bulletin of Experimental Biology and Medicine. 2003, 136(6), 588–590.

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Copyright (c) 2019 Chizhova N.D., Lipina T.V., Amstislavskaya T.G.

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