| Research Abstract |
Mammalian circadian rhythum is regulated by a pacemaker in the suprachiasmatic nuclei (SCN) of hypothalamus. The SCN containing variety of peptides. Arg-vasopressin (AVP) containing neuron is one of the output neuron of circadian signal from the SCN to the other brain area. For the entraining mechanism of pacemaker, vasoactive intestinal peptide (VIP), gastrin-releasing peptide are considered to be concerned. While the function of these peptides on the AVP release is reciprocal ; i.s.we found that the VIP increased AVP release, while gastrin-releasing peptide decreased AVP release. Photic information is the most important factor for the entrainment, which is conveyed to SCN by glutamate containing neuron. Although the glutamate is higher in SCN during the dark period, glutamate plays dark pulse type phase response curve. Light pulse induces increment of glutamate at the ventrolateral area of SCN.So, we are examining now the mechanism of glutamate release from the SCN using a biosensor, which is continuously measurable and specific to glutamate.
Beside, almost all of the SCN neuron containing GABA for an inhibitory amino-acid. GABA release shows diurnal rhythm that is higher at dark period than in light period. However the function of GABA is not clear yet. Therefore, we examined the effect of GABA on the AVP release using a slice culture system. The direct effect of GABA is not obvious, but the muscimol (GABAa-receptor agonist) increased the AVP level and bicuculline (GABAa antagonist) decreased AVP release, while the GABAb receptor agonist and/or antagonist did not show a significant effect.
In preceding to analyze the pacemaking mechanism from the transcription factor of peptides, we are screening a SCN-specific, mRNA using differential display PCR.Many mRNA from SCN found to be expressed at a constant rate throughout a day. However, a few products appeared only at CT 20-23. We are analyzing the relationship with AP-1 and cAMP levels with them.
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