[대학원 생명과학과 금요세미나 안내]
연사 : 손기훈 교수(고려대학교 의학과)
연제 : Impact of circadian nuclear receptor REV-ERBα on mood regulation
일시 : 2016년 6월 3일 (금) 오후 4시
장소 : 하나과학관 A동 109호
초청교수 : 조용철 교수
Abstract
Most physiology and behavior in mammal exhibit daily oscillations generated by an internal time-keeping system composed of interacting circadian clock proteins. The hierarchically organized circadian timing system, with a master clock in the hypothalamic suprachiasmatic nucleus (SCN) and subsidiary clocks in extra-SCN brain regions as well as peripheral organs, mediates periodicities in physiological outputs by controlling cell type-specific sets of clock-controlled genes. Circadian rhythmicity in mood regulation has been well recognized although the underlying molecular mechanisms still remain under debate. For example, disrupted circadian rhythm is frequently observed among patients with mood disorders involving the midbrain dopamine (DA) dysfunction. Furthermore, accumulating evidence strongly suggests that molecular components of the circadian timing system have a central role in mood control. We have recently demonstrated that the circadian nuclear receptor REV-ERBα, which constitutes a stabilizing feedback loop of the circadian clockwork, is heavily involved in the regulation of central DAergic system as well as mood-related behaviors. Abrogation of the Rev-erbα (Nr1d1) gene or pharmacological inhibition of REV-ERBα activity in the ventral midbrain induced mania-like phenotypes characterized by decreased depression- and anxiety-like behaviors. Subsequent transcriptome analyses revealed that key biological processes involved in neurotransmitter biosynthesis and transmission, synaptic plasticity and several intracellular signaling pathways are well organized under the control of the circadian timing system. In conclusion, our findings demonstrate that REV-ERBα links the molecular circadian clock with the mood-controlling neurotransmitter systems in the ventral midbrain, thereby having an impact on regulation and dysregulation of mood.