PMID- 25725169 OWN - NLM STAT- MEDLINE DCOM- 20150715 LR - 20150404 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 592 DP - 2015 Apr 10 TI - Sex differences in depression-like behavior after nerve injury are associated with differential changes in brain-derived neurotrophic factor levels in mice subjected to early life stress. PG - 32-6 LID - S0304-3940(15)00168-8 [pii] LID - 10.1016/j.neulet.2015.02.053 [doi] AB - We recently demonstrated that exposure to early life stress exacerbates nerve injury-induced thermal and mechanical hypersensitivity in adult male and female mice. Accumulating evidence suggests that chronic pain causes emotional dysfunction, such as anxiety and depression. In the present study, we investigated the impact of early life stress on depression-like behavior after nerve injury in mice. In addition, we examined the expression of brain-derived neurotrophic factor (BDNF), which is known to be involved in the pathogenesis of depression. Early life stress was induced by maternal separation between 2 and 3 weeks of age combined with social isolation after weaning (MSSI). At 9 weeks of age, the sciatic nerve was partially ligated to elicit neuropathic pain. Depression-like behavior was evaluated using the forced swim test at 12 weeks of age. Tissue samples from different regions of the brain were collected at the end of maternal separation (3 weeks of age) or after the forced swim test (12 weeks of age). At 12 weeks of age, immobility time in the forced swim test was increased only in MSSI-stressed female mice with nerve injury. BDNF expression was increased in male, but not female, MSSI-stressed mice at 3 weeks of age. However, MSSI stress did not impact BDNF expression in male or female mice at 12 weeks of age. Our findings suggest that exposure to early life stress exacerbates emotional dysfunction induced by neuropathic pain in a sex-dependent manner. Changes in BDNF expression after early life stress may be associated with neuropathic pain-induced depression-like behavior in adulthood. Furthermore, sex differences in BDNF expression after exposure to early life stress may contribute to sex-specific susceptibility to neuropathic pain-induced emotional dysfunction. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Nishinaka, Takashi AU - Nishinaka T AD - Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan. FAU - Kinoshita, Megumi AU - Kinoshita M AD - Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan. FAU - Nakamoto, Kazuo AU - Nakamoto K AD - Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan. FAU - Tokuyama, Shogo AU - Tokuyama S AD - Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan. Electronic address: stoku@pharm.kobegakuin.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150225 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Brain/*metabolism MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Depression/etiology/metabolism/*psychology MH - Female MH - Male MH - Maternal Deprivation MH - Mice MH - Sciatic Nerve/*injuries MH - Sex Factors MH - Social Isolation MH - Stress, Psychological/*complications OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - Depression OT - Early-life stress OT - Neuropathic pain OT - Sex difference EDAT- 2015/03/01 06:00 MHDA- 2015/07/16 06:00 CRDT- 2015/03/01 06:00 PHST- 2015/01/13 00:00 [received] PHST- 2015/02/06 00:00 [revised] PHST- 2015/02/21 00:00 [accepted] PHST- 2015/03/01 06:00 [entrez] PHST- 2015/03/01 06:00 [pubmed] PHST- 2015/07/16 06:00 [medline] AID - S0304-3940(15)00168-8 [pii] AID - 10.1016/j.neulet.2015.02.053 [doi] PST - ppublish SO - Neurosci Lett. 2015 Apr 10;592:32-6. doi: 10.1016/j.neulet.2015.02.053. Epub 2015 Feb 25.