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

点击翻译按钮获取中文摘要

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.