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Serotonin 5-HT1A, 5-HT2A, and 5-HT7 Receptors in the Brain of the BTBR Mouse the Model of Autism

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Abstract—Autism spectrum disorders (ASD) are one of the major epidemiological problems for humanity. Despite tremendous efforts undertaken by the scientific community, the mechanisms underlying ASD are still poorly understood. Evidence on the role of the brain serotonin (5-HT) system in the development of ASD is scarce and contradictory. In the present work, we investigated the functional response and expression of 5-HT1A, 5-HT2A, and 5-HT7 receptors in the brain structures of BTBR mice extensively used as an animal model to study autism. BTBR mice demonstrated a considerable decrease in 5-HT1A receptor-mediated hypothermia as compared to C57BL/6J mice. However, we found no significant differences between BTBR and C57BL/6J mice in the 5-HT1A receptor mRNA level or in the receptor protein level in all investigated brain areas. The functional response of 5-HT2A receptors, as well as the 5-НТ2А protein level, did not differ in BTBR and C57BL/6J mice. However, the 5-НТ2А receptor mRNA level was decreased in the hippocampus of BTBR mice. The functional activity, the 5-НТ7 receptor mRNA level, and protein were similar in BTBR and C57BL/6J mice. Thus, it was shown that the functional activity of the 5-HT1A receptors was considerably lower in the brain of BTBR mice with no significant changes in the expression of 5-HT1A receptors. At the same time, the expression of the 5-НТ2А receptor gene was altered with unchanged functional activity and 5-НТ2А receptor protein level. The expression and functional response of the 5-НТ7 receptors did not differ in the analyzed structures of the studied mouse strains.

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Funding

The study was supported by the Presidential grant for young Doctors of Science (project no. MD-1120.2019.4). The maintenance of the animals was supported by budget project no. 0324-2019-0041 and realized using the equipment of the Center for Genetic Resources of Laboratory Animals of the Institute of Cytology and Genetics of the Russian Academy of Sciences with the support of the Ministry of Education and Science (project ID RFMEFI62119X0023).

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    1. Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Academician Lavrent’ev Prospekt 10, 630090, Novosibirsk, Russia

      A. Ya. Rodnyy, E. A. Kulikova, E. M. Kondaurova & V. S. Naumenko

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    1. A. Ya. Rodnyy
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    2. E. A. Kulikova
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    3. E. M. Kondaurova
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    4. V. S. Naumenko
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    Correspondence to A. Ya. Rodnyy.

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    Conflict of interests. The authors declare no conflict of interests.

    Ethical approval. The maintenance of experimental animals and all procedures were performed in compliance with the international guidelines on the treatment of animals “Guide for the Care and Use of Laboratory Animals”, Eighth Edition, Committee for the Update of the Guide for the Care and Use of Laboratory Animals; National Research Council© 2011 National Academy of Sciences (United States). The use of animals was also regulated by the following documents: “Rules of good laboratory practice of the Russian Federation” approved by the Order of the Ministry of Health of the Russian Federation no. 199n of April 1, 2016; the Interstate standards GOST 33215-2014 “Guide for the Care and Use of Laboratory Animals” (Rules on the equipment of the premises and organization of procedures implemented on July 1, 2015). The environmental conditions of the animals and conducted experimental procedures were approved by the Bioethics Commission of the Institute of Cytology and Genetics of the Russian Academy of Sciences.

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    Rodnyy, A.Y., Kulikova, E.A., Kondaurova, E.M. et al. Serotonin 5-HT1A, 5-HT2A, and 5-HT7 Receptors in the Brain of the BTBR Mouse the Model of Autism. Neurochem. J. 15, 42–49 (2021). https://doi.org/10.1134/S1819712421010098

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