Dagnino-Subiabre Alexies, Orellana Juan A, Carmona-Fontaine Carlos, Montiel Juan, Díaz-Velíz Gabriela, Serón-Ferré María, Wyneken Ursula, Concha Miguel L, Aboitiz Francisco
Department of Psychiatry and Center for Medical Research, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
J Neurochem. 2006 Jun;97(5):1279-87. doi: 10.1111/j.1471-4159.2006.03787.x. Epub 2006 Mar 15.
Chronic stress affects brain areas involved in learning and emotional responses. Although most studies have concentrated on the effect of stress on limbic-related brain structures, in this study we investigated whether chronic stress might induce impairments in diencephalic structures associated with limbic components of the stress response. Specifically, we analyzed the effect of chronic immobilization stress on the expression of sympathetic markers in the rat epithalamic pineal gland by immunohistochemistry and western blot, whereas the plasma melatonin concentration was determined by radioimmunoassay. We found that chronic stress decreased the expression of three sympathetic markers in the pineal gland, tyrosine hydroxylase, the p75 neurotrophin receptor and alpha-tubulin, while the same treatment did not affect the expression of the non-specific sympathetic markers Erk1 and Erk2, and glyceraldehyde-3-phosphate dehydrogenase. Furthermore, these results were correlated with a significant increase in plasma melatonin concentration in stressed rats when compared with control animals. Our findings indicate that stress may impair pineal sympathetic inputs, leading to an abnormal melatonin release that may contribute to environmental maladaptation. In addition, we propose that the pineal gland is a target of glucocorticoid damage during stress.
慢性应激会影响参与学习和情绪反应的脑区。尽管大多数研究集中在应激对边缘系统相关脑结构的影响，但在本研究中，我们调查了慢性应激是否可能导致与应激反应边缘成分相关的间脑结构受损。具体而言，我们通过免疫组织化学和蛋白质印迹分析了慢性束缚应激对大鼠松果体上交感神经标志物表达的影响，同时通过放射免疫分析法测定血浆褪黑素浓度。我们发现，慢性应激降低了松果体中三种交感神经标志物酪氨酸羟化酶、p75神经营养因子受体和α-微管蛋白的表达，而相同处理并未影响非特异性交感神经标志物细胞外信号调节激酶1（Erk1）、细胞外信号调节激酶2（Erk2）和甘油醛-3-磷酸脱氢酶的表达。此外，与对照动物相比，这些结果与应激大鼠血浆褪黑素浓度的显著升高相关。我们的研究结果表明，应激可能损害松果体的交感神经输入，导致褪黑素释放异常，这可能导致对环境适应不良。此外，我们提出，在应激期间松果体是糖皮质激素损伤的靶点。
