On the role of 5-HT(1A) receptor gene in behavioral effect of brain-derived neurotrophic factor.
Experiments were made on a congenic AKR.CBA-D13Mit76C (76C) mouse strain created by transferring a chromosome 13 fragment containing the 5-HT1A receptor gene from a CBA strain to an AKR background. It was shown that 76C mice differed from AKR mice by decreased 5-HT1A receptor and tryptophan hydroxylase-2 (tph-2) genes expression in the midbrain. Functional activity of 5-HT2A receptors and 5-HT(2A) receptor mRNA levels in the midbrain and hippocampus of 76C mice were decreased compared with AKR mice. Central brain-derived neurotrophic factor (BDNF) administration (300 ng i.c.v.) reduced 5-HT1A and 5-HT(2A) receptor mRNA levels in the frontal cortex and tph-2 mRNA level in the midbrain of AKR mice. However, BDNF failed to produce any effect on the expression of 5-HT(1A) , 5-HT(2A) , and tph-2 genes in 76C mice but decreased functional activity of 5-HT(2A) receptors in 76C mice and increased it in AKR mice. BDNF restored social deficiency in 76C mice but produced asocial behavior (aggressive attacks towards young mice) in AKR mice. The data indicate that a small genetic variation altered the response to BDNF and show an important role of 5-HT(1A) receptor gene in the 5-HT system response to BDNF treatment and in behavioral effects of BDNF.
Department of Behavioral Neurogenomics, Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia.
Vladimir S
VS
Naumenko
Elena M
EM
Kondaurova
Daria V
DV
Bazovkina
Anton S
AS
Tsybko
Tatyana V
TV
Il'chibaeva
Nina K
NK
Popova
D000374:Aggression / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008806:Mice, Inbred AKR; D008808:Mice, Inbred CBA; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics* / Q000378:metabolism; D012919:Social Behavior
D019208:Brain-Derived Neurotrophic Factor; D044282:Receptor, Serotonin, 5-HT1A
5-HT transporter; 5-HT1A; 5-HT1A and 5-HT2A receptor functional activity; 5-HT2A receptor; BDNF; aggression; brain 5-HT system; congenic mice; tryptophan hydroxylase-2 genes expression