Accepted_test

The role of BDNF in the mechanisms of autistic-like behavior in BTBR mice
by Tatiana Ilchibaeva | Alexandra Shcherbakova | Yana Kaminskaya | Dmitry Eremin | Vladimir Naumenko | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia
Abstract ID: 59
Event: BGRS-abstracts
Sections: [Sym 7] Section “Neurogenomics and genetics of behavior”

A large number of studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of autism spectrum disorder (ASD). Data on the reduced BDNF expression in the hippocampus and the frontal cortex of BTBR mice (the model for ASD) are scarce and incomplete.
Here we investigated Bdnf exon transcripts expression as well as BDNF and its precursor proBDNF proteins in the hippocampus (HC), frontal cortex (FC), striatum (ST) and midbrain (MB) of BTBR mice in comparison with normosocial C57Bl/6 mice. The mRNA levels of Bdnf exons 1-4 were decreased in HC of BTBR mice. In the ST of BTBR mice the number of transcripts Bdnf exons 1, 2, 4 was also decreased. The mRNA levels of Bdnf exons 1 and 6 were decreased in FC of BTBR mice. The proBDNF/BDNF ratio was increased in HC and ST of BTBR mice.
I.c.v. administration of recombinant BDNF protein failed to affect the behavior of BTBR mice. Hippocampal overexpression of BDNF using AAV vectors significantly reduced anxiety-related and stereotyped behavior without affecting the social interest. Overexpression of BDNF in the FC of BTBR mice exclusively increased social interest but not other types of behaviors.
Thus, we have shown for the first time the significant changes in expression of specific Bdnf transcripts that may underlie impaired BDNF maturation in BTBR mice. Also, it was demonstrated that direct compensation of mature BDNF deficit can ameliorate autistic-like behavior in BTBR mice, but this effect is strongly dependent on the target brain structure.