The Relationship between Sleep c-fos Protein in Hypothalamus in Chronic Uremic Rats

Kim, Young Ok; Park, Chul Whee; Song, Ho Chul; Yoon, Sun Ae; Jin, Dong Chan; Kim, Yong Soo; Kim, Suk Young; Choi, Euy Jin; Chang, Yoon Sik; Bang, Byung Kee

Abstract

The activation of c-fos protein (FOS) in ventrol- ateral preoptic neuron (VLPO) induces sleep (Science 271; 216-219, 1996). Although sleep disturbance are very common in patients with chronic renal failure, its mechahanism of sleep disturbance is not clear. The purpose of this study was to evaluate sleep dissturbance and expression of FOS in VLPO of chronic uremic rats. Chronic uremic rats were induced by 5/6 nephrectomized rnodel. After 4 weeks, blood urea nitrogen and serum creatinine in uremic rats (n=14 were higher than in control (n=17) (blood urea nitrogen; 73.6+/-24.8 mg/dl vs. 23.3+/-2.9 mg/dl, P<0.001 serum creatinine', 1.49+/-0.42 mg/dl vs. 0.66+/-0.12 mg/dl, P<0.001). General activity was counted with infrared during day time (08:00-20:00) and night time (20:00-08:00). Rats were killed at 10:00 or 16:00 during day time (uremic rats 7, control 9) and at 22:00 during night time (uremic rats 7, control 7). The expression of FOS in VLPO was examined with immunohistochernical method. The number of day tirne general activity in uremic rats was significantly higher than in control (458+/-185 vs. 222+/-41, P<0.001), and the number of night time general activity in uremic rats was lower than in control (949+/- 430 vs. 1618+/-261, P<0.001). During day time, the number of FOS immunoreactive cell in uremic rats was lower than in control (18.4+/-5.3 vs. 42.8+/-6.3, P<0.001), but there was no difference between 2 groups at night time (10.8+/-8.4 vs 12.5+/-5.1, P=0.62). There was strong negative correlation between the number of activity and the number of FOS immunoreactive cell in control (r= -0.93, P<0.001), but there was no correlation in uremic rats. This study shows that sleep disturbance in chronic uremic rats might be related to decrease of expression of FOS in VLPO.