Sex-specific and region-specific changes in BDNF-TrkB signalling in the hippocampus of 5-HT1A receptor and BDNF single and double mutant mice

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• 作者：YeeWen Candace Wu^a ; ^b ; Rachel A. Hill^a ; ^c ; ^{hillr@unimelb.edu.au} ; Maren Klug^a ; ^d ; Maarten van den Buuse^a ; ^b
• 关键词：Sex difference ; BDNF ; 5-HT1A ; Hippocampus ; Depression
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：3 May, 2012
• 卷：1452
• 期：Complete
• 页码：10-17
• 文件大小：582 K

摘要

Brain-derived neurotrophic factor (BDNF) and serotonin 5-HT1A receptors are implicated in the pathophysiology of depression and the mechanism of action of antidepressant drugs. Here, we explore possible reciprocal interactions of 5-HT1A receptor knockout and the expression of BDNF, its receptor TrkB and downstream mitogen-activated protein kinase (MAPK) in the ventral (VHP) and dorsal hippocampus (DHP). We compared female and male double mutant mice (5-HT1A^{鈭?鈭?/sup>/BDNF+/鈭?/sup>) with single mutant mice (5-HT1A鈭?鈭?/sup>, BDNF+/鈭?/sup>) and wildtype (WT) controls. Protein expression of BDNF, TrkB, phosphorylation of TrkB (pTrkB) and MAPKs (ERK1, ERK2) was examined using Western blot analysis (n = 5-7). As expected, the BDNF+/鈭?/sup> mice showed ~ 50%BDNF reduction. Loss of 5-HT1A receptors induced a significant decrease in BDNF levels in the VHP in female mice. The pTrkB/TrkB ratio was also significantly decreased in female 5-HT1A鈭?鈭?/sup> mice and 5-HT1A鈭?鈭?/sup>/BDNF+/鈭?/sup> mice but not in males. Despite markedly reduced BDNF levels in BDNF+/鈭?/sup> mice and double mutants, ERK1 activation was unchanged in the female mice. In contrast, ERK2 activation was significantly elevated in the VHP of female BDNF+/鈭?/sup> mice and double mutants. Given the greater vulnerability of women to develop depression and the role of the VHP in stress responses and anxiety-related behaviours, our results may shed more light on sex differences in depression and other psychiatric disorders with BDNF and 5-HT1A receptor dysfunction.}