Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 34, Pages 12527-12532Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0804340105
Keywords
little SAAS; neuropeptides; solid-phase extraction; peptidomics; suprachiasmatic nucleus
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Funding
- NHLBI NIH HHS [R01 HL086870] Funding Source: Medline
- NIDA NIH HHS [P30 DA018310, R01 DA 017940, R01 DA017940, P30 DA 018310] Funding Source: Medline
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A significant challenge to understanding dynamic and heterogeneous brain systems lies in the chemical complexity of secreted intercellular messengers that change rapidly with space and time. Two solid-phase extraction collection strategies are presented that relate time and location of peptide release with mass spectrometric characterization. Here, complex suites of peptide-based cell-to-cell signaling molecules are characterized from the mammalian suprachiasmatic nucleus (SCN), site of the master circadian clock. Observed SCN releasates are peptide rich and demonstrate the corelease of established circadian neuropeptides and peptides with unknown roles in circadian rhythms. Additionally, the content of SCN releasate is stimulation specific. Stimulation paradigms reported to alter clock timing, including electrical stimulation of the retinohypothalamic tract, produce releasate mass spectra that are notably different from the spectra of compounds secreted endogenously over the course of the 24-h cycle. In addition to established SCN peptides, we report the presence of proSAAS peptides in releasates. One of these peptides, little SAAS, exhibits robust retinohypothalannic tract-stimulated release from the SCN, and exogenous application of little SAAS induces a phase delay consistent with light-mediated cues regulating circadian timing. These mass spectrometry-based analyses provide a new perspective on peptidergic signaling within the SCN and demonstrate that the integration of secreted compounds with information relating time and location of release generates new insights into intercellular signaling in the brain.
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