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開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Mifepistone improves a dysfunction of hypothalamus-pituitary-adrenal axis in SART-stressed mice

  • P3-184
  • 船上 仁範 / Yoshinori Funakami:1 宮本 朋佳 / Tomoyoshi Miyamoto:1 阪井 邦正 / Kunimasa Sakasi:1 植芝 慧子 / Keiko Ueshiba:1 西坂 香名子 / Kanako Nishisaka:1 和田 哲幸 / Tetsuyuki Wada:1 市田 成志 / Seiji Ichida:1 
  • 1:近畿大学 / Division of Biochemistry, Faculty of Pharmacy, Kinki University 

It has been known that chronic stress is related to the onset of mental, circulatory and digestive diseases. Especially, glucocorticoids play an important role in a function of the hypothalamic-pituitary-adrenal (HPA) axis and stress-related mental disease. However, the mechanism by which cause an activation of the HPA axis in chronic stress response is still unknown. The specific alternation of rhythm in temperature (SART)-stressed animal which shows various chronic stress symptoms is considered a model for autonomic imbalance. The aim of this study was to investigate the neural activity of paraventricular hypothalamic nucleus (PVN) and a function of HPA axis via glucocorticoids receptor (GR) in the SART-stressed mice. Male ddY mice were orally administered GR antagonist, mifepristone (20mg/kg/day) during the SART stress loading as follows. Mice were transferred between 24°C room's cage and 4°C room's cage hourly from 9:00 to 16:00 and housed in a cage at 4°C from l6:00 to 09:00 the following morning. This procedure was repeated for 8 days up to 11:30 on the final day. After the mice were given a cold exposure for an hour, each mice was intracardially perfused with saline followed by 4% paraformaldehyde in PBS under isoflurane anesthesia. Removed brains were treated for immunohistochemistry to count c-Fos (an indicator of neuronal activity) positive cells in the PVN. The corticosterone (CORT) level in serum was measured by EIA. The CORT level and the amount of c-Fos expression were significantly increased by acute cold stress in mice. However, these parameters were unchanged in SART-stressed mice. In SART-stressed mice, mifepristone increased the amount of c-Fos expression in PVN and the serum CORT levels. In summary, stress response to acute cold stress was supressed in SART-stressed mice. It was considered that this abnormal response was related to autonomic imbalance and chronic stress symptoms, because mifepristone improved the decreased serum CORT level and neuronal activity of PVN which is the starting point in the HPA axis. These results suggest the possibility that the SART stress supressed the function of the HPA axis via GR receptor in the PVN.

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