Fos expression in the suprachiasmatic nucleus in rats following high altitude exposure

INTRODUCTION: Disturbances of circadian rhythms occur at high altitude. We examined the suprachiasmatic nucleus (SCN), considered to be the biological clock in mammals that regulates circadian rhythmicity, in adult rats following an exposure to simulated high altitude. METHODS: Male adult Wistar rats weighing 250 g were exposed to an altitude of 8000 m in an altitude chamber, following which they were sacrificed at various time intervals ranging from 45 min to 3 d. Normal rats of similar weight kept outside the chamber were used as controls. Sections of hypothalamus containing the suprachiasmatic nucleus were processed immunohistochemically for expression of Fos, neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS). RESULTS: At 45 min, 4 h, and 24 h following the altitude exposure, a large number of Fos-positive neurons were detected as compared with the control rats in which occasional Fos-positive neurons were observed. Increased expression of nNOS and eNOS was also observed at 45 min and 4 h following the altitude exposure. CONCLUSIONS: It is suggested that the neuronal activation indicated by upregulated expression of Fos and nitric oxide (NO) generated by nNOS may be involved in the disturbed circadian rhythms of the cardiovascular system (e.g., heart rate and BP), hormone secretion, and sleep-wake cycle which occur frequently during sojourns to high altitude. Increased eNOS expression also indicates excess production of NO, which may be involved in vasodialation and increased blood flow to the SCN following the exposure and may also be involved in modulating the circadian rhythms at high altitude.