Journal
BRAIN RESEARCH
Volume 1452, Issue -, Pages 10-17Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2012.03.011
Keywords
Sex difference; BDNF; 5-HT1A; Hippocampus; Depression
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Funding
- University of Melbourne
- National Health and Medical Research Council of Australia [566879]
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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(-/-)/BDNF+/-) with single mutant mice (5-HT1A(-/-), BDNF+/-) 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+/- 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(-/-) mice and 5-HT1A(-/-)/BDNF+/- mice but not in males. Despite markedly reduced BDNF levels in BDNF+/- 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+/- 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. (C) 2012 Elsevier B.V. All rights reserved.
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