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 imme diate early genes in that they are rapidly induced by different kinds of stimuli in the nervous system. These two proteins bind to DNA regul ating 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 weig ht) rats, kept under a 12h/12h light-dark cycle, were sacrificed every 4h starting at 07(00). The expression of c-fos, c-jun and jun B mRNAs was studied in six different brain areas by means of Northern blot hy bridization, c-fos expression was also studied with in situ hybridizat ion and immunohistochemistry. In basal conditions c-fos expression dis played 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 stri atum, whereas c-jun mRNA remained constantly high throughout 24 h. The periodicity of c-fos and jun B oscillation persisted also when the an imals were exposed for 6 days to constant (24 h/24 h) light or darknes s. 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 wh ether the expression of fos and jun could be correlated with states of wakefulness (W) and sleep (S), monitored with EEG recording under beh avioral control. The results of these experiments demonstrated that c- fos mRNA is high during W and almost absent during S. Similar findings were obtained in the study of jun B expression in the cortex, whereas c-jun expression remained high with no significant variations between S and W. Altogether these data demonstrate that the expression of c-f os and jun B varies during 24h in relation to the S-W cycle. The findi ng that the expression of DNA transcription regulatory factors is asso ciated with behavioral and electrical patterns of S and W may represen t a first step in understanding the molecular events that characterize these two different physiological states.