Prepro-hypocretin (prepro-orexin) expression is unaffected by short-term sleep deprivation in rats and mice

The hypocretin/orexin ligand-receptor system has recently been implicated i n the sleep disorder narcolepsy. During the dark (active) period, null muta nts of the prepro-orexin (prepro-hypocretin) gene have cataplectic attacks and increased levels of both rapid eye movement (REM) and non-REM (NREM) sl eep. Intracerebroventricular injection of one of the encoded neuropeptides, orexin-A, early in the light period increases wakefulness and reduces REM sleep in the rat, suggesting that this system may be involved in the normal regulation of sleep and wakefulness. To further test this hypothesis, we m easured hypocretin (hcrt) mRNA levels by both Northern hybridization and Ta qman analysis in mouse and rat hypothalamus after short-term (6 h) sleep de privation (SD) and 2-4 hours after recovery from SD. Although our SD proced ures effectively induced a sleep debt and increased c-fos mRNA expression i n the cortex and hypothalamus as described by other investigators, we found that hcrt mRNA levels were not significantly changed in either species eit her after SD or after recovery from SD. if the hcrt system is involved in n ormal regulation of sleep and wakefulness, longer periods of SD may be nece ssary to affect hcrt mRNA levels or changes may occur at the protein rather than mRNA level. Alternatively, this system may also be involved in anothe r function that counterbalances any SD-induced changes in hcrt mRNA levels.