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

Abstract

The hypothalamic suprachiasmatic nucleus (SCN) functions as a circadian pacemaker regulating a variety of physiological and behavioral rhythms in mammals. Retinal illumination evokes expression of several immediate-early genes, including junB, in the ventral SCN early in the subjective night and throughout the SCN later in the subjective night. junB mRNA and protein are also expressed spontaneously around subjective dawn in nocturnal rodents, but only in the dorsal SCN. We examined the biochemical signaling mechanisms underlying both spontaneous and light-evoked expression of junB mRNA in the SCN of Syrian hamsters. Hamsters were injected (i.p.) before subjective dawn with vehicle or with either tyrphostin or genistein, inhibitors of protein tyrosine kinase, and maintained in the dark for 30 min. They were then exposed to a light pulse or kept in darkness for another 30 min. In situ hybridization 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 tyrosine kinase sensitive to tyrphostin but not to genistein is involved in the transduction pathways leading to expression of junB mRNA selectively in the dorsal SCN, independently of circadian phase and independently of the involvement of light.