Changes in 5-HT2A-mediated behavior and 5-HT2A- and 5-HT1A receptor binding and expression in conditional brain-derived neurotrophic factor knock-out mice.
Changes in 5-HT2A-mediated behavior and 5-HT2A- and 5-HT1A receptor binding and expression in conditional brain-derived neurotrophic factor knock-out mice.
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DOI：
10.1016/j.neuroscience.2010.05.054
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发表时间：
2010-09-01
期刊：
影响因子：
3.3
通讯作者：
Rios, M.
中科院分区：
文献类型：
--
作者：
Klein, A. B.;Santini, M. A.;Aznar, S.;Knudsen, G. M.;Rios, M.
Changes in brain-derived neurotrophic factor (BDNF) expression have been implicated in the etiology of psychiatric disorders. To investigate pathological mechanisms elicited by perturbed BDNF signaling, we examined mutant mice with central depletion of BDNF (BDNF2L/2LCk-cre). A severe impairment specific for the serotonin 2A receptor (5-HT2A) in prefrontal cortex was described previously in these mice. This is of much interest, as 5-HT2A receptors have been linked to neuropsychiatric disorders and in anxiety-related behavior. Here we further characterized the serotonin receptor alterations triggered by BDNF depletion. 5-HT2A (3H-MDL100907) and 5-HT1A (3H-WAY100635) receptor autoradiography revealed site-specific alterations in BDNF mutant mice. They exhibited lower 5-HT2A receptor binding in frontal cortex but increased binding in hippocampus. Additionally, 5-HT1A receptor binding was decreased in hippocampus of BDNF mutants, but unchanged in frontal cortex. Molecular analysis indicated corresponding changes in 5-HT2A and 1A mRNA expression but normal 5-HT2C content in these brain regions in BDNF2L/2LCk-cre mice. We investigated whether the reduction in frontal 5-HT2A receptor binding was reflected in reduced functional output in two 5-HT2A-receptor mediated behavioral tests, the head-twitch response (HTR) and the ear-scratch response (ESR). BDNF2L/2LCk-cre mutants treated with the 5-HT2A receptor agonist DOI showed a clearly diminished ESR but no differences in HTR compared to wildtypes. These findings illustrate the context-dependent effects of deficient BDNF signaling on the 5-HT receptor system and 5-HT2A-receptor functional output.
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影响因子：
6.7
作者：
Savitz J;Lucki I;Drevets WC
通讯作者：
Drevets WC
DOI：
10.1074/jbc.m801713200
发表时间：
2008-06-20
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Yuen EY;Jiang Q;Chen P;Feng J;Yan Z
通讯作者：
Yan Z
影响因子：
4.7
作者：
Deltheil, T.;Guiard, B. P.;Gardier, A. M.
通讯作者：
Gardier, A. M.
影响因子：
1.7
作者：
Thomsen, C;Helboe, L
通讯作者：
Helboe, L
影响因子：
3.3
作者：
Chan, J. P.;Unger, T. J.;Rios, M.
通讯作者：
Rios, M.