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 induced in neuronal populations responsible for specific sleep-wake states. The 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 have a selective reduction in slow-wave sleep. This suggests that a build-up of c-fos during wakefulness increases the drive to sleep and lack of c-fos is associated with reduced sleep. Sleep also has an effect on c-Fos serving to eliminate the protein rapidly. Waxing and waning of transcription factors such as c-Fos may influence slow, oscillating events such as sleep and wakefulness. To further examine what role c-Fos may play in regulating sleep, the present study examined the effects of prolonged wakefulness on c-Fos and AP-1 activity in young (3.5 months old) and old (21.5 months old) Sprague--Dawley rats. Previously we found that old rats slept less even after prolonged wakefulness, and other investigators have found that aging is also associated with a decline in c-Fos. In the present study, we reasoned that prolonged wakefulness would also fail to increase c-Fos in old versus young rats. The baseline levels of c-Fos and AP-1 activity were not different between young and old rats. However, in response to 6 or 12 h of prolonged wakefulness, old rats demonstrated significantly less c-Fos and AP-1 activity compared to young rats. These findings suggest that in old rats the mechanism responsible for c-Fos induction in response to wakefulness is deficient. Such a decline at the molecular level could contribute to the decline in sleep that typically occurs with age.
Basheer
R
R
VA Medical Center and Harvard Medical School, 1400 VFW Parkway, West Roxbury, MA 02132, USA.
Shiromani
P J
PJ
D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D017781:Genes, Immediate-Early / Q000502:physiology; D006179:Gyrus Cinguli / Q000737:chemistry / Q000378:metabolism; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012895:Sleep, REM / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000378:metabolism*; D014851:Wakefulness / Q000502:physiology*
D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1