Disrupted Sleep Homeostasis and Altered Expressions of Clock Genes in Rats with Chronic Lead Exposure.

Sleep disturbance is one of the neurobehavioral complications of lead neurotoxicity. The present study evaluated the impacts of chronic lead exposure on alteration of the sleep-wake cycle in association with changes of clock gene expression in the hypothalamus. Sprague-Dawley rats with chronic lead exposure consumed drinking water that contained 250 ppm of lead acetate for five weeks. Electroencephalography and electromyography were recorded for scoring the architecture of the sleep-wake cycle in animals. At six Zeitgeber time (ZT) points (ZT2, ZT6, ZT10, ZT14, ZT18, and ZT22), three clock genes, including , , and , were analyzed. The rats with chronic lead exposure showed decreased slow wave sleep and increased wakefulness in the whole light period (ZT1 to ZT12) and the early dark period (ZT13 to ZT15) that was followed with a rebound of rapid-eye-movement sleep at the end of the dark period (ZT22 to ZT24). The disturbance of the sleep-wake cycle was associated with changes in clock gene expression that was characterized by the upregulation of and and the feedback repression of . We concluded that chronic lead exposure has a negative impact on the sleep-wake cycle in rats that predominantly disrupts sleep homeostasis. The disruption of sleep homeostasis was associated with a toxic effect of lead on the clock gene expression in the hypothalamus.