Different programs of gene expression are associated with different phases of the 24h and sleep-wake cycles

The Fos and Jun proteins are encoded by proto-oncogenes acting as immediate early genes in that they are rapidly induced by different kinds of stimuli in the nervous system. These two proteins bind to DNA regulating gene transcription, and thus determining the specificity of the neuronal response to the applied stimulation. We investigated whether the expression of these genes undergoes a variation during 24h in the absence of exogenous stimulation. Male Wistar adult (200 gr. body weight) rats, kept under a 12h/12h light-dark cycle, were sacrificed every 4h starting at 0700. The expression of c-fos, c-jun and jun B mRNAs was studied in six different brain areas by means of Northern blot hybridization, c-fos expression was also studied with in situ hybridization and immunohistochemistry. In basal conditions c-fos expression displayed a highly significant spontaneous oscillation, with the highest level during the darkness hours and the lowest during the light hours. Parallel levels of jun B expression were found in the cortex and striatum, whereas c-jun mRNA remained constantly high throughout 24 h. The periodicity of c-fos and jun B oscillation persisted also when the animals were exposed for 6 days to constant (24h/24h) light or darkness. Such oscillation could instead be inverted by manipulating the rest-activity cycle, i.e. keeping the animals awake during the light hours and allowing them to sleep during the dark hours. We then verified whether the expression of fos and jun could be correlated with states of wakefulness (W) and sleep (S), monitored with EEG recording under behavioral control.(ABSTRACT TRUNCATED AT 250 WORDS)