The Possible Role of c-fos Protein in Hypothalamus in Sleep Disturbance in Chronic Uremic Rats

Abstract

Sleep disturbance is very common in patients with chronic renal failure, but its mechanism is not clear. The activity of c-fos protein (FOS) in ventrolateral preoptic neurons (VLPO) is associated with the sleep pattern. The purpose of this study was to evaluate the relationship between sleep disturbance and the expression of FOS in VLPO of chronic uremic rats. Chronic uremia was induced by the 5/6 nephrectomized model. The movements of the rats were measured with infrared monitoring during the daytime (8.00–20.00) and nighttime (20.00–8.00). Rats were killed at 10.00 or 16.00 h for the daytime (uremic rats 7, control 8) and at 22.00 h for the nighttime (uremic rats 7, control 9). The expression of FOS in VLPO was examined with the immunohistochemical method. The number of recorded daytime movements in uremic rats was significantly higher than in control rats (458 ± 185 vs. 222 ± 41, p < 0.001), but the number of recorded nighttime movements in uremic rats was lower than in control rats (949 ± 430 vs. 1,618 ± 261, p < 0.001). In the daytime, the number of FOS immunoreactive cells in uremic rats was lower than in control rats (18.4 ± 5.3 vs. 42.8 ± 6.3, p < 0.001), but there was no difference between two groups in the nighttime (10.8 ± 8.4 vs. 12.5 ± 5.1, p = 0.62). There was a strong negative correlation between the number of recorded movements and the number of FOS immunoreactive cells in VLPO (r = –0.700, p < 0.001). This finding suggests that sleep disturbances in chronic uremic rats might be related to the decreased expression of FOS in VLPO.