Selective regional blockade of junB gene expression in the hamster suprachiasmatic nucleus by a tyrosine kinase inhibitor

The hypothalamic suprachiasmatic nucleus (SCN) functions as a circadian pac emaker regulating a variety of physiological and behavioral rhythms in mamm als. Retinal illumination evokes expression of several immediate-early gene s, including junB, in the ventral SCN early in the subjective night and thr oughout the SCN later in the subjective night, junB mRNA and protein are al so expressed spontaneously around subjective dawn in nocturnal rodents, but only in the dorsal SCN. We examined the biochemical signaling mechanisms u nderlying both spontaneous and light-evoked expression of junB mRNA in the SCN of Syrian hamsters. Hamsters were injected (i.p.) before subjective daw n with vehicle or with either tyrphostin or genistein, inhibitors of protei n tyrosine kinase, and maintained in the dark for 30 min. They were then ex posed to a light pulse or kept in darkness for another 30 min. In situ hybr idization studies demonstrated that tyrphostin pretreatment (12 or 24 mg/kg ) reduced both spontaneous and light-evoked expression of junB mRNA only in the dorsal, and not the ventral, portion of the SCN. Conversely, genistein had little effect on either spontaneous or light-evoked expression of junB mRNA in any part of the SCN. These results indicate that a protein tyrosin e kinase sensitive to tyrphostin but not to genistein is involved in the tr ansduction pathways leading to expression of junB mRNA selectively in the d orsal SCN, independently of circadian phase and independently of the involv ement of light. (C) 2000 Published by Elsevier Science B.V. All rights rese rved.