Chamas Firas M, Underwood Mark D, Arango Victoria, Serova Lidia, Kassir Suham A, Mann John J, Sabban Esther L
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
Biol Psychiatry. 2004 Feb 1;55(3):278-83. doi: 10.1016/s0006-3223(03)00788-1.
Stress triggers adaptive and maladaptive changes in the central nervous system, including activation of the hypothalamic-pituitary-adrenal axis, and can trigger mood disorders and posttraumatic stress disorder. We examined the effect of immobilization stress (IMO) on gene expression of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, and the role of cortisol in that response.
Regular and adrenalectomized Sprague-Dawley rats were exposed to various repetitions of IMO. Tryptophan hydroxylase messenger ribonucleic acid (mRNA) was determined by competitive reverse transcriptase polymerase chain reaction, and TPH protein was examined by immunoblot and immunocytochemistry.
Elevation of TPH mRNA by IMO was tissue-specific and dose-dependent. A single IMO elicited a threefold rise in TPH mRNA in median raphe nucleus (MRN), but repeated (3x) IMOs were needed for similar response in dorsal raphe nucleus (DRN). Repeated daily IMO, up to 7 days, triggered a robust induction (6-10-fold) in TPH mRNA, accompanied by corresponding rise in TPH protein levels in raphe nuclei but not in the pineal gland. The rise in TPH immunoreactivity was widespread throughout the DRN and MRN. Bilateral adrenalectomy did not prevent the IMO-triggered increase in TPH immunoreactive protein in the raphe nuclei.
This study reveals adrenal glucocorticoid-independent induction of TPH gene expression in raphe nuclei in response to immobilization stress.
应激会引发中枢神经系统的适应性和适应不良性变化，包括下丘脑-垂体-肾上腺轴的激活，并可引发情绪障碍和创伤后应激障碍。我们研究了制动应激（IMO）对色氨酸羟化酶（TPH）基因表达的影响，TPH是血清素生物合成中的限速酶，以及皮质醇在该反应中的作用。
将正常和肾上腺切除的Sprague-Dawley大鼠暴露于不同次数的IMO。通过竞争性逆转录聚合酶链反应测定色氨酸羟化酶信使核糖核酸（mRNA），并通过免疫印迹和免疫细胞化学检测TPH蛋白。
IMO引起的TPH mRNA升高具有组织特异性和剂量依赖性。单次IMO使中缝正中核（MRN）中的TPH mRNA升高三倍，但背侧中缝核（DRN）需要重复（3次）IMO才能产生类似反应。每天重复IMO，持续7天，会引发TPH mRNA的强烈诱导（6-10倍），同时中缝核中TPH蛋白水平相应升高，但松果体中没有。TPH免疫反应性的升高在整个DRN和MRN中广泛存在。双侧肾上腺切除术并不能阻止IMO引发的中缝核中TPH免疫反应性蛋白的增加。
本研究揭示了在制动应激反应中，中缝核中TPH基因表达的诱导不依赖肾上腺糖皮质激素。
