Disrupted circadian rhythm in rats with nephrectomy-induced chronic kidney disease

Abstract

Aims: Our study investigated the role of circadian rhythm in the pathogenesis of sleep disturbance in patients with chronic kidney disease (CKD) based on an animal model.

Main methods: Sixteen Sprague-Dawley (SD) rats (eight from 5/6 nephrectomized CKD group and eight from control group) were used for electroencephalography (EEG) and electromyography (EMG) recording. Eight rats (four from CKD and four from control group) were sacrificed at six Zeitgeber time (ZT) points and determined the mRNA expression of clock genes, rPer1, rPer2 and rBMAL1b in the hypothalamus.

Key findings: Our results demonstrated that both slow wave sleep (SWS) and rapid eye movement (REM) sleep were significantly increased in the ZT22-24 Zeitgeber time point of the dark period in the CKD rats when compared with those sleep architectures obtained from the control rats. The CKD-induced sleep disruptions were associated with significant upregulations of rPer1 (in ZT2, ZT6 and ZT14) and rPer2 mRNA expression (in ZT2 and ZT14) in the hypothalamus.

Significance: Our study elucidated that the increases of SWS and REM sleep during ZT22-24 of the dark period in the CKD rats might be due to the enhancement of rPer1 and rPer2 clock genes in the hypothalamus, suggesting that disrupted circadian rhythm plays a role in the pathogenesis of sleep disturbance in patients with CKD.