Effects of prolonged wakefulness on c-fos and AP1 activity in young and old rats

Recent studies have demonstrated that the immediate-early gene c-fos is ind uced in neuronal populations responsible for specific sleep-wake states. Th e induction of this gene may be functionally relevant to sleep homeostasis since without the gene mice (c-fos null) take longer to fall asleep and hav e a selective reduction in slow-wave sleep. This suggests that a build-up o f c-fos during wakefulness increases the drive to sleep and lack of c-fos i s associated with reduced sleep. Sleep also has an effect on c-Fos serving to eliminate the protein rapidly. Waxing and waning of transcription factor s such as c-Fos may influence slow, oscillating events such as sleep and wa kefulness. To further examine what role c-Fos may play in regulating sleep, the present study examined the effects of prolonged wakefulness on c-Fos a nd AP-1 activity in young (3.5 months old) and old (21.5 months old) Spragu e-Dawley rats. Previously we found that old rats slept less even after prol onged wakefulness, and other investigators have found that aging is also as sociated with a decline in c-Fos. In the present study. we reasoned that pr olonged wakefulness would also fail to increase c-Fos in old versus young r ats. The baseline levels of c-Fos and AP-1 activity were not different betw een young and old rats. However. in response to 6 or 12 h of prolonged wake fulness, old rats demonstrated significantly less c-Fos and AP-1 activity c ompared to young rats. These findings suggest that in old rats the mechanis m responsible for c-Fos induction in response to wakefulness is deficient. Such a decline at the molecular level could contribute to the decline in sl eep that typically occurs with age. (C) 2001 Elsevier Science B.V. Ail righ ts reserved.