Alterations in glutamatergic signaling contribute to the decline of circadian photoentrainment in aged mice

Biello, S. M. , Bonsall, D. R., Atkinson, L. A., Molyneux, P. C., Harrington, M. E. and Lall, G. S. (2018) Alterations in glutamatergic signaling contribute to the decline of circadian photoentrainment in aged mice. Neurobiology of Aging, 66, pp. 75-84. (doi: 10.1016/j.neurobiolaging.2018.02.013) (PMID:29547750)

Abstract

Robust physiological circadian rhythms form an integral part of well-being. The aging process has been found to negatively impact systems that drive circadian physiology, typically manifesting as symptoms associated with abnormal/disrupted sleeping patterns. Here, we investigated the age-related decline in light-driven circadian entrainment in male C57BL/6J mice. We compared light-driven resetting of circadian behavioral activity in young (1-2 months) and old (14-18 months) mice and explored alterations in the glutamatergic pathway at the level of the circadian pacemaker, the suprachiasmatic nucleus (SCN). Aged animals showed a significant reduction in sensitivity to behavioral phase resetting by light. We show that this change was through alterations in N-Methyl-D-aspartate (NMDA) signaling at the SCN, where NMDA, a glutamatergic agonist, was less potent in inducing clock resetting. Finally, we show that this shift in NMDA sensitivity was through the reduced SCN expression of this receptor's NR2B subunit. Only in young animals did an NR2B antagonist attenuate behavioral resetting. These results can help target treatments that aim to improve both physiological and behavioral circadian entrainment in aged populations.

• Item Type: Articles
• Additional Information: This work was supported, in part, by funding from the following sources: Royal Society UK (RG100842) to GSL, Research grant award from the University of Kent to DRB and GSL, NIH EARDA (Smith College) and NIH NIA 5P01AG009975-18 both to MEH.
• Keywords: Aging, circadian rhythm, glutamate, NMDA, NR2B.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Biello, Professor Stephany
• Authors: Biello, S. M., Bonsall, D. R., Atkinson, L. A., Molyneux, P. C., Harrington, M. E., and Lall, G. S.
• College/School: College of Science and Engineering > School of Psychology
• Journal Name: Neurobiology of Aging
• Publisher: Elsevier
• ISSN: 0197-4580
• ISSN (Online): 1558-1497
• Published Online: 20 February 2018
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Neurobiology of Aging 66: 75-84
• Publisher Policy: Reproduced under a Creative Commons License