Light deprivation damages monoamine neurons and produces a depressive behavioral phenotype in rats
Light deprivation damages monoamine neurons and produces a depressive behavioral phenotype in rats
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DOI：
10.1073/pnas.0703615105
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发表时间：
2008-03-25
影响因子：
11.1
通讯作者：
Aston-Jones, G.
中科院分区：
文献类型：
--
作者：
Gonzalez, M. M. C.;Aston-Jones, G.
光是调节情绪的重要环境因素。在光照有限的高纬度地区，季节性情感障碍的发生率很高，明亮的光线疗法是一种成功的抗抑郁治疗方法。我们最近发现，大鼠保持在恒定的黑暗（DD）6周的解剖和行为特征类似于抑郁症患者，包括昼夜睡眠-觉醒节律失调和去甲肾上腺素（NA）蓝斑（LC）系统的损害。在这里，我们分析了神经系统的细胞活力与抑郁症的病理生理后DD，包括NA-LC，多巴胺能中缝核和腹侧被盖区神经元，并评估了光剥夺大鼠的抑郁行为。我们发现增加细胞凋亡的三个胺能系统分析时，与动物保持6周，在12：12光暗条件下。NA-LC神经元中观察到最多的凋亡，与皮质NA终扣数量的显著减少相关。在行为上，DD诱导抑郁样的条件下，通过增加不动强迫游泳试验（FST）。DD似乎没有压力（对肾上腺或体重没有影响），但可能对随后的压力源有敏感反应（FST期间粪便数量增加）。我们还发现，抗抑郁药地昔帕明减少了光剥夺对神经和行为的影响。这些发现表明，DD诱导单胺脑系统的神经损伤，这种损伤与抑郁行为表型有关。我们的研究结果表明了一种机制，即长时间有限的光照强度可能会对情绪产生负面影响。
Light is an important environmental factor for regulation of mood. There is a high frequency of seasonal affective disorder in high latitudes where light exposure is limited, and bright light therapy is a successful antidepressant treatment. We recently showed that rats kept for 6 weeks in constant darkness (DD) have anatomical and behavioral features similar to depressed patients, including dysregulation of circadian sleep-waking rhythms and impairment of the noradrenergic (NA)-locus coeruleus (LC) system. Here, we analyzed the cell viability of neural systems related to the pathophysiology of depression after DD, including NA-LC, serotoninergic-raphe nuclei and dopaminergic-ventral tegmental area neurons, and evaluated the depressive behavioral profile of light-deprived rats. We found increased apoptosis in the three aminergic systems analyzed when compared with animals maintained for 6 weeks in 12:12 light-dark conditions. The most apoptosis was observed in NA-LC neurons, associated with a significant decrease in the number of cortical NA boutons. Behaviorally, DD induced a depression-like condition as measured by increased immobility in a forced swim test (FST). DD did not appear to be stressful (no effect on adrenal or body weights) but may have sensitized responses to subsequent stressors (increased fecal number during the FST). We also found that the antidepressant desipramine decreases these neural and behavioral effects of light deprivation. These findings indicate that DD induces neural damage in monoamine brain systems and this damage is associated with a depressive behavioral phenotype. Our results suggest a mechanism whereby prolonged limited light intensity could negatively impact mood.