No evidence of brain cell degeneration after long-term sleep deprivation in rats

Sleep deprivation leads to cognitive impairments in humans and, if sustaine d for 2-3 weeks in rats, it is invariably fatal. It has been suggested that neural activity associated with waking, if it is not interrupted by period s of sleep, may damage brain cells through excitotoxic or oxidative mechani sms and eventually lead to cell death. To determine whether sustained wakin g causes brain cell degeneration, three parallel strategies were used. The presence and extent of DNA fragmentation was analyzed with the TUNEL techni que on brain sections from rats sleep deprived for various periods of time (from 8 h to 14 days) and From their respective controls. Adjacent sections from the same animals were stained with a newly developed fluorochrome (Fl uoro-Jade) specific for degenerating neurons. Finally, total RNA from the c erebral cortex of the same animals was used to determine whether the expres sion of several stress response genes and apoptosis-related genes is modifi ed after sustained waking. In most long-term sleep deprived rats only a few scattered TUNEL positive nuclei (1-3) were found in any given brain sectio n. The overall number, distribution, and morphology of TUNEL positive cells in long-term sleep deprived rats did not differ significantly from yoked c ontrols, shea-term sleep deprived rats, and sleep controls. No evidence of degenerating neurons as detected by Fluoro-Jade was found in any experiment al group. mRNA levels of all the stress response genes and apoptosis-relate d genes tested did not differ between long-term sleep deprived rats and the ir yoked controls. These results argue against the hypothesis that sustaine d waking can significantly damage brain cells through excitotoxic or oxidat ive mechanisms and that massive cell death may explain the fatal consequenc es of sleep deprivation. (C) 1999 Elsevier Science B.V. All rights reserved .