Enriched environments influence depression-related behavior in adult mice and the survival of newborn cells in their hippocampi
Enriched environments influence depression-related behavior in adult mice and the survival of newborn cells in their hippocampi
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DOI：
10.1016/j.bbr.2007.02.036
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发表时间：
2007-06-04
影响因子：
2.7
通讯作者：
Kunugi, Hiroshi
中科院分区：
文献类型：
--
作者：
Hattori, Satoko;Hashimoto, Ryota;Kunugi, Hiroshi
重度抑郁症是一种非常普遍的精神障碍，环境因素与其病理生理学密切相关。临床研究表明，压力或抑郁会导致海马体萎缩和细胞丢失。对抑郁症动物模型的研究表明，成年海马体神经发生的减少可能导致这种结构变化和这些动物的行为。另一方面，服用抗抑郁药或电惊厥可以诱导海马神经发生的增加，这表明神经发生的增加可能与抑郁症的治疗有关。因此，丰富的环境（EE）也能增强神经发生，预计对抑郁相关行为具有治疗作用。为了研究成年小鼠 EE 对这些行为的影响，我们对在 EE 中饲养五周的成年小鼠进行了行为测试。在旷场测试中，EE 小鼠的行走距离减少，在中心停留的时间增加。 EE 小鼠的惊吓反应比对照小鼠小。 EE 小鼠在强迫游泳测试中也表现出不动时间减少。 EE 小鼠的不动时间大约是用三环类抗抑郁药丙咪嗪治疗的小鼠的一半。在我们的实验条件下，通过 5-溴-2'-脱氧尿苷 (BrdU) 标记的免疫组织化学观察到 EE 小鼠新生细胞存活率增加。 BrdU 和成熟神经元标记 NeuN 的双重染色显示，大多数存活细胞是神经元。我们的结果表明，EE 可以增强新生神经元的存活率，对行为绝望和适应新环境显示出有益的作用。 (c) 2007 Elsevier B.V. 保留所有权利。
Major depression is a highly prevalent mental disorder and environmental factors have been strongly implicated in its pathophysiology. Clinical studies have demonstrated that stress or depression can lead to atrophy and cell loss in the hippocampus. Studies of animal models of depression have suggested that reduced neurogenesis in the adult hippocampus might contribute to such structural changes and to the behavior of these animals. On the other hand, increased hippocampal neurogenesis can be induced by the administration of antidepressants or electroconvulsive seizure, suggesting that increased neurogenesis might be related to the treatment of depression. Thus, an enriched environment (EE), which also enhances neurogenesis, is expected to have therapeutic effects on depression-related behaviors. To investigate the effects of an EE during adulthood on these behaviors, we subjected adult mice housed in an EE for five weeks to behavioral tests. In an open field test, EE mice exhibited a decrease in the distance traveled and an increase in the amount of time spent in the center. The startle response was smaller in EE mice than in control mice. EE mice also showed reduced immobility time in a forced swim test. The immobility time in EE mice was approximately half that observed in mice treated with a tricyclic antidepressant, imipramine. In our experimental condition, increased survival of newborn cells was observed in EE mice by 5 -bromo-2'-deoxyuri dine (BrdU)-labeled immunohistochemistry. Double-staining of BrdU and a mature neuron marker, NeuN, revealed that the majority of surviving cells were neurons. Our results suggest that EE, which enhanced the survival of newborn neurons, shows beneficial effects on behavioral despair and habituation to a novel environment. (c) 2007 Elsevier B.V. All rights reserved.