Characterizing cerebellin-short, a novel circadian peptide, in the rat suprachiasmatic nucleus

Circadian;Rat;Suprachiasmatic Nucleus: SCN;peptide;Mass Spectrometry Imaging;Long Term Potentiation

Chu, James L.

关键词: Circadian;    Rat;    Suprachiasmatic Nucleus: SCN;    peptide;    Mass Spectrometry Imaging;    Long Term Potentiation;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/101126/CHU-DISSERTATION-2018.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Circadian rhythms in mammals, such as metabolism, hormone release, and the sleep/wake cycle, are orchestrated by the suprachiasmatic nucleus (SCN) located in the hypothalamus. Mass spectrometry peptidomics of the SCN identified the small peptide cerebellin-short (SGSAKBSAIRSTN) consisting of 15 amino acids, which is released from the SCN in circadian fashion. Cerebellin-short is the C-terminus truncated form of the 16 amino acid cerebellin peptide highly enriched in the cerebellum. The distribution of cerebellin-short in the SCN and the functional implications of its circadian release, however, are unknown. Here we showed that the precursor of cerebellin-short, Cbln1, is expressed in the SCN with daily oscillations in mRNA level. The level of Cbln1 process intermediate also oscillates around the day. Immunofluorescence revealed that a portion of both AVP- and VIP- positive cells in the SCN are also positive for cerebellin-short. Cbln1 on the other hand localized immediately dorsal to the SCN along the 3rd ventricle. Cbln1 also showed strong localization to the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the median eminence. No Cbln1 or process intermediate were observed in GFAP-positive astrocytes. Crude synaptosome fractionations of the SCN revealed that the processing intermediate, but not Cbln1, is enriched at the synapse. Exogenous application of cerebellin-short at midday and early night phase advance the spontaneous firing rhythm of SCN neurons. These results suggest that Cbln1 is actively processed into cerebellin-short at the synapses throughout the SCN, and is likely involved in the intrinsic circadian time keeping mechanism.