The effect of corticosterone/MR signaling on exercise-induced neurogenesis in dentate area

• Main Authors: Ya-ting Chang, 張雅婷
• Other Authors: Yu-min Kuo
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/88746591969946568279

碩士 === 國立成功大學 === 細胞生物及解剖學研究所 === 95 === Adult mammalian neurogenesis has been well accepted in two brain areas: subventricular zone (SVZ) and subgranular zone (SGZ) of hippocampal dentate area. Physical exercise is known to enhance neurogenesis, although the underlying mechanism remains unclear. Glucocorticoids (corticosterone in rodent), secreted by adrenal cortex, is known to influence neurogenesis. As serum corticosterone is affected by physical exercise, an involvement of corticosterone in exercise-induced neurogenesis is hypothesized. The treadmill running (TR) paradigm was adopted to accurately define the intensity and duration of exercise. The result showed that 5 weeks TR increased transiently serum corticosterone levels; whereas the level of hippocampal mineralcorticoid receptor (MR), one of two corticosterone receptors, was down-regulated. The concentration of the other corticosterone receptor, glucocorticoid receptor (GR), remained unaltered. Accordingly, the TR-induced neurogenesis in dentate area were evaluated at two different settings: (1) transient elevation of corticosterone and (2) down-regulation of MR. The result indicated that single intraperitoneal (i.p.) corticosterone injection of 4mg/kg gave a serum corticosterone concentration resembling the TR-induced corticosterone elevation. Therefore, the effect of transient elevation of corticosterone on the neuronal progenitor proliferation in dentate area was investigated in mice that received daily corticosterone (4mg/kg, i.p.) injection for three weeks. The results indicated that such treatment did not change the number of neuronal progenitor in dentate area. Nor did the expression levels of hippocampal BDNF and MR, both were affected by TR, changed. These findings suggested that transient corticosterone elevation did not contribute to the TR-induced proliferation of neuronal progenitors in dentate area. To examine whether the down-regulation of MR is involved in the TR-induced neurogenesis, animals were treated with a selective MR antagonist, spironolactone (100mg/kg/day) for three weeks. The results showed that spironolactone significantly enhanced TR-induced progenitor cell number in the dentate area, while it did not change the level of hippocampal BDNF. Further studies showed that the MR antagonist did not change the number of cell proliferation but increased that of immature neuron. In conclusion, these results suggest that the phenomenon of TR-induced neurogenesis in the dentate area is partially due to the inhibition of corticosterone/MR signaling which subsequently enhances the neuronal differentiation and shows no correlation with the BDNF expression.