Effects of 5-ht1A receptor overexpression in the frontal cortex on autism-like behavior and the expression of 5-ht1A, 5-ht7 receptors and bdnf in btbr mice

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Abstract

Autism spectrum disorders (ASD) are the most common neurodevelopmental disorders, however, their mechanisms are still poorly understood. Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are known as key players in the regulation of brain plasticity and behavior. Among the variety of 5-HT receptors, the most interesting is the 5-HT1A receptor, which is the main regulator of the brain 5-HT system functioning. In this work, we investigated the effect of 5-HT1A receptor overexpression in the frontal cortex induced by the administration of the adeno-associated virus pAAV-Syn-HTR1A-eGFP to BTBR T+ Itpr3tf/J (BTBR) mice, a model of autism, on autism-like behavior and on the expression of the Htr1a gene transcription factor – Freud-1 (encoded by the Cc2d1a gene), its intracellular signal transducer ERK1/2 (encoded by the Mapk3 gene), 5-HT7 receptors, mature BDNF, proBDNF and TrkB and p75NTR receptors. Overexpression of the 5-HT1A receptor had no effect on time in the center and locomotor activity in the open field test, social behavior in the three-chamber test, immobility time in the tail suspension test, and associative learning in the “operant wall” paradigm, but it enhanced the severity of stereotyped behavior in the marble burying test. 5-HT1A receptor overexpression in the frontal cortex did not affect the mRNA and protein levels of 5-HT7 receptors, mature BDNF, proBDNF and TrkB and p75NTR receptors in the cortex and hippocampus of BTBR mice. However, overexpression caused an increase in the protein level of the transcription factor Freud-1 in the hippocampus without changing the mRNA level of Cc2d1a in the frontal cortex and hippocampus. No changes in the pERK/ERK ratio were found in both investigated brain structures. Thus, the results of this study indicate a possible disruption in interactions of: 5-HT1A receptors with downstream intracellular signal transducers; 5-HT system, BDNF and TrkB receptors; and 5-HT1A and 5-HT7 receptors in the frontal cortex of BTBR mice.

About the authors

E. M. Kondaurova

Institute of Cytology and Genetics, Siberian Branch of RAS

Email: chudabest@gmail.com
Novosibirsk, Russia

Y. D. Grigorieva

Institute of Cytology and Genetics, Siberian Branch of RAS

Email: chudabest@gmail.com
Novosibirsk, Russia

I. I. Belokopytova

Institute of Cytology and Genetics, Siberian Branch of RAS

Email: chudabest@gmail.com
Novosibirsk, Russia

E. A. Kulikova

Institute of Cytology and Genetics, Siberian Branch of RAS

Email: chudabest@gmail.com
Novosibirsk, Russia

A. S. Tsybko

Institute of Cytology and Genetics, Siberian Branch of RAS

Email: chudabest@gmail.com
Novosibirsk, Russia

N. V. Khotskin

Institute of Cytology and Genetics, Siberian Branch of RAS

Email: chudabest@gmail.com
Novosibirsk, Russia

T. V. Ilchibaeva

Institute of Cytology and Genetics, Siberian Branch of RAS

Email: chudabest@gmail.com
Novosibirsk, Russia

N. K. Popova

Institute of Cytology and Genetics, Siberian Branch of RAS

Email: chudabest@gmail.com
Novosibirsk, Russia

V. S. Naumenko

Institute of Cytology and Genetics, Siberian Branch of RAS

Author for correspondence.
Email: chudabest@gmail.com
Novosibirsk, Russia

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