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RAS PhysiologyНейрохимия Neurochemical Journal

  • ISSN (Print) 1027-8133
  • ISSN (Online) 3034-5561

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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PII
S30345561S1027813325010088-1
DOI
10.7868/S3034556125010088
Publication type
Article
Status
Published
Authors
E. M. Kondaurova
  • Affiliation: Institute of Cytology and Genetics, Siberian Branch of RAS
Yu. D. Grigorieva
  • Affiliation: Institute of Cytology and Genetics, Siberian Branch of RAS
I. I. Belokopytova
  • Affiliation: Institute of Cytology and Genetics, Siberian Branch of RAS
E. A. Kulikova
  • Affiliation: Institute of Cytology and Genetics, Siberian Branch of RAS
A. S. Tsybko
  • Affiliation: Institute of Cytology and Genetics, Siberian Branch of RAS
N. V. Khotskin
  • Affiliation: Institute of Cytology and Genetics, Siberian Branch of RAS
T. V. Ilchibaeva
  • Affiliation: Institute of Cytology and Genetics, Siberian Branch of RAS
N. K. Popova
  • Affiliation: Institute of Cytology and Genetics, Siberian Branch of RAS
V. S. Naumenko
  • Affiliation: Institute of Cytology and Genetics, Siberian Branch of RAS
Volume/ Edition
Volume 42 / Issue number 1
Pages
104-122
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.
Keywords
серотониновая система 5-HT1A-рецептор 5-HT7-рецептор BDNF pERK/ERK AAV-опосредованная сверхэкспрессия расстройства аутистического спектра аутистическое поведение мыши линии BTBR
Date of publication
03.03.2025
Year of publication
2025
Number of purchasers
0
Views
250

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