Overexpression of Brain-Derived Neurotrophic Factor (BDNF) in the Frontal Cortex Enhances Social Interest in BTBR Mice, a Model of Autism

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Abstract

A large body of evidence implicates brain-derived neurotrophic factor (BDNF) in the pathogenesis of autism spectrum disorders (ASD). A number of studies have noted BDNF deficiency in the hippocampus and frontal cortex of BTBR mice, which are a model of autism. We have previously shown that induction of BDNF overexpression in the hippocampus of BTBR mice reduces anxiety and the severity of stereotypic behavior, but does not affect social interest. In the present study, we induced BDNF overexpression in frontal cortical neurons of BTBR mice using an adeno-associated viral vector. We found a significant increase in social interest in the three-chamber social test in animals from the experimental group. At the same time, no changes were revealed in stereotypy, exploratory and anxiety-like behavior, as well as novel object recognition. Thus, we have shown for the first time that the BDNF in the frontal cortex is critically important for the expression of social interest in BTBR mice, since compensation for its deficiency in this structure eliminates the autism-like disorder of social behavior characteristic for these animals.

About the authors

Y. P. Kaminskaya

Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Email: antoncybko@mail.ru
Russian Federation, 630090 Novosibirsk

T. V. Ilchibaeva

Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Email: antoncybko@mail.ru
Russian Federation, 630090 Novosibirsk

A. I. Shcherbakova

Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Email: antoncybko@mail.ru
Russian Federation, 630090 Novosibirsk

E. R. Allayarova

Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Email: antoncybko@mail.ru
Russian Federation, 630090 Novosibirsk

N. K. Popova

Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Email: antoncybko@mail.ru
Russian Federation, 630090 Novosibirsk

V. S. Naumenko

Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Email: antoncybko@mail.ru
Russian Federation, 630090 Novosibirsk

A. S. Tsybko

Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Author for correspondence.
Email: antoncybko@mail.ru
Russian Federation, 630090 Novosibirsk

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