The roles and regulatory mechanisms of expression of proto-oncogenes in the nervous system

立即早期基因（IEGs）被各种细胞外刺激物反式激活。这些基因的蛋白质产物是将膜去孔与细胞功能的长期改变联系起来的转录因子。它们被认为在神经可塑性和再生中起重要作用。在本研究中，我们研究了这些IEG在大脑和非神经组织中的表达模式，并揭示了这些IEG的转录在各种类型的细胞中受到差异调节。先前反复制动应力抑制这些IEGs的表达，但NGFI-A在大脑中，包括下丘脑室旁核在响应挑战的压力。我们还发现，血浆糖皮质激素水平升高具有相同的影响，重复性应激对这些IEG的调节。还检测了视皮层中c-fos和NGFI-A对短暂光照的反应。NGFI-A总是在光暴露和神经激活的反应中表达，而c-fos在正常饲养的大鼠中对光暴露没有反应，但只有在黑暗饲养一周后才有反应。这些发现表明，定期重复刺激抑制c-fos的反应性的刺激。我们还观察到在非神经元细胞和组织中的IEGs的表达，并发现固定应激引起心肌细胞、冠状动脉上皮细胞或胃上皮细胞中IEGs的瞬时表达。再生的角膜上皮和骨骼肌细胞也短暂表达这些IEG。IEG的生理相关性将在我们未来的研究中使用基因操纵的胺进行调查。

Immediate early genes (IEGs) are transactivated by various extracellylar stimuli. Protein products of these genes are transcription factors which link membrane deporization to long-term alterations of cellular functions. They are considered to play important roles in the neural plasticity and regeneration. In the present study, we investigated the expression patterns of these IEGs in the brain and in non-neural tissues and revealed that transcription of these IEGs is differentially regulated in various types of cells. Prior repeated immobilization stress suppresses expression of these IEGs but NGFI-A in the brain including the hypothalamic paraventricular nucleus in response to challenge stress. We also found that an elevated plasma glucocorticoid level has the same effects as repetitive stress on the regulation of these IEGs. Expression of c-fos and NGFI-A was also examined in the visual cortex in response to brief light exposure. NGFI-A was always expressed in response to light exposure and neural activation, while c-fos did not respond to light exposure in normally reared rats but responded to it only after dark rearing for one week. These findings suggest that regularly repeated stimuli suppress the responsiveness of c-fos to the stimulus. We also observed expression of IEGs in non-neuronal cells and tissues and found that immobilization stress causes transient expression of IEGs in heart muscle cells, epithelial cells of coronary arteries, or in the epithelial cells of the stomach. Regenerating corneal epithelium and skeletal muscle cells also transiently expressed these IEGs. The physiological relevance of IEGs will be investigated in our future studies using gene-manipulated aminals.