Abstract
BackgroundNeuropeptides are critical integrative elements within the central circadian clock in the suprachiasmatic nucleus (SCN), where they mediate both cell-to-cell synchronization and phase adjustments that cause light entrainment. Forward peptidomics identified little SAAS, derived from the proSAAS prohormone, among novel SCN peptides, but its role in the SCN is poorly understood.Methodology/Principal FindingsLittle SAAS localization and co-expression with established SCN neuropeptides were evaluated by immunohistochemistry using highly specific antisera and stereological analysis. Functional context was assessed relative to c-FOS induction in light-stimulated animals and on neuronal circadian rhythms in glutamate-stimulated brain slices. We found that little SAAS-expressing neurons comprise the third most abundant neuropeptidergic class (16.4%) with unusual functional circuit contexts. Little SAAS is localized within the densely retinorecipient central SCN of both rat and mouse, but not the retinohypothalamic tract (RHT). Some little SAAS colocalizes with vasoactive intestinal polypeptide (VIP) or gastrin-releasing peptide (GRP), known mediators of light signals, but not arginine vasopressin (AVP). Nearly 50% of little SAAS neurons express c-FOS in response to light exposure in early night. Blockade of signals that relay light information, via NMDA receptors or VIP- and GRP-cognate receptors, has no effect on phase delays of circadian rhythms induced by little SAAS.Conclusions/SignificanceLittle SAAS relays signals downstream of light/glutamatergic signaling from eye to SCN, and independent of VIP and GRP action. These findings suggest that little SAAS forms a third SCN neuropeptidergic system, processing light information and activating phase-shifts within novel circuits of the central circadian clock.
Highlights
The hypothalamic suprachiasmatic nucleus (SCN) orchestrates daily rhythms in brain and body functions and aligns them with environmental day and night, processes fundamental to health and longevity [1]
Little SAAS localizes to the central SCN of rat and mouse We evaluated brain tissues from rat and mouse by fluorescence immunohistochemistry for known peptide markers while staining for little SAAS immunoreactivity
Little SAAS localization is less apparent in regions marked by vasoactive intestinal polypeptide (VIP) than in the central area marked by gastrinreleasing peptide (GRP) in these mid-SCN sections
Summary
The hypothalamic suprachiasmatic nucleus (SCN) orchestrates daily rhythms in brain and body functions and aligns them with environmental day and night, processes fundamental to health and longevity [1] Functions coordinated by this master circadian clock are diverse: behavioral rhythms of activity and rest, peak performance in memory acquisition, release of pituitary hormones into the portal system, oscillations in autonomic functions, time of stem cell migration from the bone marrow into the blood stream, and even disease vulnerabilities. Because we live in an ever-changing world, the SCN must integrate ambient timing cues and, if necessary, adjust its time-base to re-align brain and body processes These requirements impose exceptional modulatory demands at the input, intra-SCN and output levels on the neurons and circuits that comprise the master clock. Forward peptidomics identified little SAAS, derived from the proSAAS prohormone, among novel SCN peptides, but its role in the SCN is poorly understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
