Hattori Satoko, Hashimoto Ryota, Miyakawa Tsuyoshi, Yamanaka Hajime, Maeno Hiroshi, Wada Keiji, Kunugi Hiroshi
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
Behav Brain Res. 2007 Jun 4;180(1):69-76. doi: 10.1016/j.bbr.2007.02.036. Epub 2007 Feb 28.
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'-deoxyuridine (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.
重度抑郁症是一种高度流行的精神障碍，环境因素在其病理生理学中起着重要作用。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，成年海马体中神经发生减少可能导致这种结构变化以及这些动物的行为改变。另一方面，给予抗抑郁药或电惊厥发作可诱导海马体神经发生增加，这表明神经发生增加可能与抑郁症的治疗有关。因此，丰富环境（EE），它也能增强神经发生，有望对与抑郁相关的行为产生治疗作用。为了研究成年期丰富环境对这些行为的影响，我们将成年小鼠置于丰富环境中饲养五周后进行行为测试。在旷场试验中，丰富环境组小鼠的行进距离减少，在中央区域停留的时间增加。丰富环境组小鼠的惊吓反应比对照组小鼠小。在强迫游泳试验中，丰富环境组小鼠的不动时间也减少。丰富环境组小鼠的不动时间约为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）标记免疫组织化学观察到丰富环境组小鼠新生细胞的存活率增加。BrdU与成熟神经元标记物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，丰富环境可提高新生神经元的存活率，对行为绝望和对新环境的适应具有有益影响。
