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Functional Peptidomics: Stimulus- and Time-of-Day-Specific Peptide Release in the Mammalian Circadian Clock
ACS Chemical Neuroscience ( IF 5 ) Pub Date : 2018-06-14 00:00:00 , DOI: 10.1021/acschemneuro.8b00089
Norman Atkins , Shifang Ren , Nathan Hatcher , Penny W. Burgoon , Jennifer W. Mitchell , Jonathan V. Sweedler , Martha U. Gillette

Daily oscillations of brain and body states are under complex temporal modulation by environmental light and the hypothalamic suprachiasmatic nucleus (SCN), the master circadian clock. To better understand mediators of differential temporal modulation, we characterize neuropeptide releasate profiles by nonselective capture of secreted neuropeptides in an optic nerve horizontal SCN brain slice model. Releasates are collected following electrophysiological stimulation of the optic nerve/retinohypothalamic tract under conditions that alter the phase of the SCN activity state. Secreted neuropeptides are identified by intact mass via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). We found time-of-day-specific suites of peptides released downstream of optic nerve stimulation. Peptide release was modified differentially with respect to time-of-day by stimulus parameters and by inhibitors of glutamatergic or PACAPergic neurotransmission. The results suggest that SCN physiology is modulated by differential peptide release of both known and unexpected peptides that communicate time-of-day-specific photic signals via previously unreported neuropeptide signatures.

中文翻译:

功能性肽组学:哺乳动物昼夜节律时钟中刺激和一天中特定时间的肽释放。

脑和身体状态的每日振荡受环境光和下丘脑超生物钟(SCN)(昼夜节律生物钟)的复杂时间调节。为了更好地理解时差调节的介体,我们通过视神经水平SCN脑切片模型中分泌神经肽的非选择性捕获来表征神经肽释放谱。在视神经/视网膜下丘脑束的电生理刺激之后,在改变SCN活动状态阶段的条件下收集释放物。通过基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF MS)通过完整质量鉴定分泌的神经肽。我们发现一天特定时间的一组肽在视神经刺激的下游释放。通过刺激参数和谷氨酸能或PACAP能神经传递抑制剂,相对于一天中的时间差异地改变了肽的释放。结果表明,SCN生理受到已知和意想不到的肽的差异肽释放的调节,这些肽通过先前未报告的神经肽信号传递特定时间的光信号。
更新日期:2018-06-14
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