The effect of enriched environment across ages: A study of anhedonia and BDNF gene induction.
The effect of enriched environment across ages: A study of anhedonia and BDNF gene induction.
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DOI：
10.1111/gbb.12485
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Sakata K
中科院分区：
文献类型：
--
作者：
Dong BE;Xue Y;Sakata K
丰富环境治疗（EET）是通过诱导脑源性神经营养因子（BDNF）来治疗抑郁症的潜在干预措施。然而，其年龄依赖性仍不清楚。我们最近发现，生命早期发育（ED）期间的 EET 可有效增加探索活动和抗绝望行为，特别是在启动子 IV 驱动的 BDNF 缺陷小鼠（KIV）中，海马和额叶皮层的 BDNF 蛋白诱导最多。在这里，我们通过使用蔗糖偏好测试和 qRT-PCR 进一步确定了 EET 对快感缺乏和启动子特异性 BDNF 转录的影响的年龄依赖性。野生型 (WT) 和 KIV 小鼠在 ED、青年期和老年期（分别为 0-2、2-4 和 12-14 个月）接受两个月的 EET。所有 KIV 组均表现出对蔗糖的偏好降低，无论年龄大小，EET 均能逆转这一现象。 EET 增加了所有年龄和基因型的海马 BDNF mRNA 水平，但仅增加了 ED KIV 和老年 WT 小鼠的额叶皮层 BDNF mRNA 水平。 WT 小鼠海马中启动子 I 和 IV 的转录具有年龄依赖性：分别在 ED 或老年期间更有效地诱导外显子 IV 或 I。几乎所有 9 个启动子的转录在额叶皮层中都是年龄特异性的，主要在 ED KIV 小鼠中观察到。停止使用 EET 后，EET 对两个区域的抗快感缺失和 BDNF 转录的作用仅在 ED KIV 小鼠中持续存在。这些结果表明，EET 在逆转快感缺乏和诱导海马 BDNF 转录方面同样有效，但在 ED 期间诱导额叶皮层 BDNF 转录以及持久抗快感缺乏和 BDNF 作用（特别是在启动子 IV-BDNF 缺乏的情况下）更有效。
Enriched environment treatment (EET) is a potential intervention for depression by inducing brain-derived neurotrophic factor (BDNF). However, its age dependency remains unclear. We recently found that EET during early-life development (ED) was effective in increasing exploratory activity and anti-despair behavior, particularly in promoter IV-driven BDNF deficient mice (KIV), with the largest BDNF protein induction in the hippocampus and frontal cortex. Here, we further determined age dependency of EET effects on anhedonia and promoter-specific BDNF transcription, by using the sucrose preference test and qRT-PCR. Wild-type (WT) and KIV mice received two months of EET during ED, young-adulthood and old-adulthood (0–2, 2–4, and 12–14 months, respectively). All KIV groups showed reduced sucrose preference, which EET equally reversed regardless of age. EET increased hippocampal BDNF mRNA levels for all ages and genotypes, but increased frontal cortex BDNF mRNA levels only in ED KIV and old WT mice. Transcription by promoters I and IV was age-dependent in the hippocampus of WT mice: more effective induction of exon IV or I during ED or old-adulthood, respectively. Transcription by almost all 9 promoters was age-specific in the frontal cortex, mostly observed in ED KIV mice. After discontinuance of EET, the EET effects on anti-anhedonia and BDNF transcription in both regions persisted only in ED KIV mice. These results suggested that EET was equally effective in reversing anhedonia and inducing hippocampal BDNF transcription, but was more effective during ED in inducing frontal cortex BDNF transcription and for lasting anti-anhedonic and BDNF effects particularly in promoter IV-BDNF deficiency.
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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：
3.7
作者：
Inui-Yamamoto C;Yamamoto T;Ueda K;Nakatsuka M;Kumabe S;Inui T;Iwai Y
通讯作者：
Iwai Y
影响因子：
10.6
作者：
Hing, Benjamin;Davidson, Scott;Lear, Marrisa;Breen, Gerome;Quinn, John;McGuffin, Peter;MacKenzie, Alasdair
通讯作者：
MacKenzie, Alasdair
DOI：
10.1523/jneurosci.5057-08.2009
发表时间：
2009-02-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Arai JA;Li S;Hartley DM;Feig LA
通讯作者：
Feig LA
影响因子：
4.2
作者：
Adlard, PA;Perreau, VM;Cotman, CW
通讯作者：
Cotman, CW