Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV.
Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV.
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DOI：
10.1038/tp.2016.160
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发表时间：
2016-09-20
影响因子：
6.8
通讯作者：
Sakata K
中科院分区：
文献类型：
--
作者：
Jha S;Dong BE;Xue Y;Delotterie DF;Vail MG;Sakata K
启动子IV驱动的脑源性神经营养因子(BDNF)表达减少与应激和严重抑郁症有关。我们之前曾报道，缺陷启动子IV(KIV)导致幼年成年小鼠的抑郁样行为，丰富环境治疗(EET)比抗抑郁药更有效地逆转这种行为。启动子IV-BDNF缺乏和EET对生命阶段的影响尚不清楚。由于早期生命发育(ED)涉及动态的表观遗传过程，我们假设ED期间的EET将提供最大的抗抑郁作用，由于增强的、持久的BDNF诱导，这种作用将在以后的生命中持续存在。我们通过测定三个生命阶段的EET效应来验证这一假说：ED(0-2个月)、年轻人(2-4个月)和老年人(12-14个月)。与野生型小鼠相比，所有生命阶段的KIV小鼠在旷场和尾部悬吊试验中表现出抑郁样行为。两个月的EET减少了ED和年轻成年小鼠的抑郁样行为，但不减少老年成年小鼠的抑郁样行为，其中以ED KIV小鼠的效果最大。这一作用仅在ED小鼠停止EET后持续1个月。在ED小鼠中，EET诱导的BDNF蛋白在海马区和额叶皮质中也是最大的，并且在EET停止后仅在ED KIV小鼠的海马区持续存在。没有观察到性别差异的影响。结果表明，启动子IV缺陷会导致抑郁样行为，无论年龄和性别，ED期间的EET对启动子IV-BDNF缺乏的个体特别有益，而老年人可能需要额外的治疗。
Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0–2 months), young adult (2–4 months), and old adult (12–14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults.
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影响因子：
10.6
作者：
Autry, Anita E.;Adachi, Megumi;Cheng, Pengfei;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
3
作者：
Cutuli D;Caporali P;Gelfo F;Angelucci F;Laricchiuta D;Foti F;De Bartolo P;Bisicchia E;Molinari M;Farioli Vecchioli S;Petrosini L
通讯作者：
Petrosini L
影响因子：
2.7
作者：
Duman, Catharine H.;Schlesinger, Lee;Terwilliger, Rosemarie;Russell, David S.;Newton, Samuel S.;Duman, Ronald S.
通讯作者：
Duman, Ronald S.
影响因子：
4.2
作者：
Adlard, PA;Perreau, VM;Cotman, CW
通讯作者：
Cotman, CW
影响因子：
2.7
作者：
Chourbaji, S;Zacher, C;Gass, P
通讯作者：
Gass, P