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Reduced Expression of Slc Genes in the VTA and NAcc of Male Mice with Positive Fighting Experience

Dmitry A. Smagin, View ORCID ProfileVladimir N. Babenko, View ORCID ProfileIrina L. Kovalenko, View ORCID ProfileAnna G. Galyamina, View ORCID ProfileOlga E. Redina, View ORCID ProfileNatalia N. Kudryavtseva
doi: https://doi.org/10.1101/2020.11.10.377523
Dmitry A. Smagin
1Laboratory of Neuropathology Modeling, The FRC Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
2Neurogenetics of Social Behavior Sector, The FRC Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
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Vladimir N. Babenko
1Laboratory of Neuropathology Modeling, The FRC Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
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Irina L. Kovalenko
1Laboratory of Neuropathology Modeling, The FRC Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
2Neurogenetics of Social Behavior Sector, The FRC Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
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Anna G. Galyamina
1Laboratory of Neuropathology Modeling, The FRC Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
2Neurogenetics of Social Behavior Sector, The FRC Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
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Olga E. Redina
1Laboratory of Neuropathology Modeling, The FRC Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
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Natalia N. Kudryavtseva
1Laboratory of Neuropathology Modeling, The FRC Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
2Neurogenetics of Social Behavior Sector, The FRC Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
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  • For correspondence: n.n.kudryavtseva@gmail.com smagin@bionet.nsc.ru
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ABSTRACT

There are many psychiatric medications targeting the activity of SLC transporters. Therefore, further research is needed to elucidate the expression profiles of the Slc* genes, which may serve as markers of altered brain metabolic processes and neurotransmitter activities in psychoneurological disorders. We studied differentially expressed Slc genes using the transcriptomic profiles in the ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) of male mice with psychosis-like behavior induced by repeated aggression experience in daily agonistic interactions which are accompanied by wins. Most of differentially expressed Slc genes in the VTA and NAcc (12 of 17 and 25 of 26, respectively) were downregulated, which was not the case in the PFC (6 and 5, up- and down, respectively). Also, the majority of these genes were shown to have brain region-specific expression profiles. In the VTA and NAcc altered expression was observed for the genes encoding the transporters of neurotransmitters as well as inorganic and organic ions, amino acids, metals, glucose, etc. This means alteration in transport functions for many substrates, which results in complete disruption of all cellular and neurotransmitter processes. The neurotransmitter systems, especially, the dopaminergic one, in male mice with positive fighting experience in daily agonistic interactions undergo changes leading to profound genomic modifications which include downregulated expression of the majority of the Slc* genes at least in the VTA and NAcc, which is attributable to chronic stimulation of the reward systems.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Grant information: Russian Science Foundation, grant No. 19-15-00026, FRC ICG SB RAS: BP No 0324-2019-0041-C-01

  • Abbreviations

    MSN
    Medium Spiny Neurons;
    Slc*
    solute carrier family;
    PCA
    Principal Component Analysis;
    AHC
    Agglomerative Hierarchical Clustering;
    FPKM
    fragments per kilobase of transcript per million mapped reads;
    VTA
    ventral tegmental area;
    NAcc
    nucleus accumbens;
    PFC
    prefrontal cortex.
    W
    winners;
    C
    controls.
  • Copyright 
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    Reduced Expression of Slc Genes in the VTA and NAcc of Male Mice with Positive Fighting Experience
    Dmitry A. Smagin, Vladimir N. Babenko, Irina L. Kovalenko, Anna G. Galyamina, Olga E. Redina, Natalia N. Kudryavtseva
    bioRxiv 2020.11.10.377523; doi: https://doi.org/10.1101/2020.11.10.377523
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    Reduced Expression of Slc Genes in the VTA and NAcc of Male Mice with Positive Fighting Experience
    Dmitry A. Smagin, Vladimir N. Babenko, Irina L. Kovalenko, Anna G. Galyamina, Olga E. Redina, Natalia N. Kudryavtseva
    bioRxiv 2020.11.10.377523; doi: https://doi.org/10.1101/2020.11.10.377523

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