Copper in the suprachiasmatic circadian clock: A possible link between multiple circadian oscillators.

摘要: The mammalian circadian clock in the suprachiasmatic nucleus (SCN) is very robust, able to coordinate our daily physiological and behavioral rhythms with exquisite accuracy. Simultaneously, SCN highly sensitive environmental timing cues such as solar cycle. This duality of resiliency sensitivity may be sustained part by a complex intertwining three cellular oscillators: transcription/translation, metabolic/redox, membrane excitability. We suggest here that one links connecting these oscillators forged from copper (Cu). Cellular Cu levels are regulated brain peripherally, affects metabolism, redox state, cell signaling, transcription. have shown both chelation application induce nighttime phase shifts vitro treatments affect glutamate, N-methyl-D-aspartate receptor, associated signaling processes differently. More recently we found induces mitogen-activated protein kinase-dependent shifts, while mechanisms which removal remain unclear. Lastly, two transporters expressed SCN, (ATP7A) exhibits day/night rhythm. Our results homeostasis tightly changes serve time cue for clock. discuss findings light existing literature current models multiple coupled SCN.