CRF受体对五羟色胺系统的调节作用及早期环境因素的影响

早期环境因素持续影响脑与行为的发展,增加个体成年后应激相关精神疾病患病的易感性.应激反应的中枢启动因子促肾上腺皮质激素释放因子(corticotropin-releasing factor,CRF)通过两种受体CRF1和CRF2调节中缝背核(dorsal raphe nucleus,DRN)-五-羟色胺(serotonin,5-HT)系统,后者已被证实在应激相关情绪疾患发病和治疗过程中发挥重要作用.已知CRF受体以相互影响相互拮抗的方式动态调节DRN-5-HT系统,提示这两种受体相对作用的调节对于协调复杂环境中DRN-5-HT系统的应激反应过程起着关键性作用.早期环境因素和遗传因素交互作用导致CRF受体的分布和反应性持续改变并造成DRN-5-HT系统反应异常,可能是导致应激反应和精神疾病易感性个体差异的重要神经基础.

The Roles of CRF Receptors in the Modulation of Serotoninergic System and the Effects of Early Environmental Factors

Early environmental factors had long-term effects on the development of brain and behaviors, and led to a variety of psychopathological changes. It is well known that the dorsal raphe nucleus (DRN)-serotonin (5-HT) system is implicated in the onset and treatment of stress-related psychiatric disorders. Corticotropin-releasing factor (CRF) modulates activity of this system during stress via activation of two receptors: CRF1 and CRF2. CRF1 and CRF2 mediated inhibition and excitation of the DRN-5-HT system respectively. Therefore, the regulation of the relative contribution of the two CRF receptors to brain CRF pathways may be essential in coordinating 5-HTergic responses to stress. The early environmental factors (e.g. stress) induced long-term even lifetime changes in the distribution and reactivity of CRF receptors, and the DRN-5-HT system response to further stressful stimuli, which might be involved in the individual differences of susceptibility to stress-related psychiatric disorders.