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

Biello, Stephany M., Bonsall, David R., Atkinson, Lynsey A., Molyneux, Penny, Harrington, Mary, Lall, Gurprit S. (2018) Alterations in glutamatergic signalling contribute to the decline of circadian photoentrainment in aged mice. Neurobiology of Aging, 66 . pp. 75-84. ISSN 0197- 4580. (doi:10.1016/j.neurobiolaging.2018.02.013)

Abstract

Robust physiological circadian rhythms form an integral part of wellbeing. 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 behavioural 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 behavioural phase-resetting by light. We show that this change was through alterations in NMDA signalling 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 behavioural resetting. These results can help target treatments that aim to improve both physiological and behavioural circadian entrainment in aged populations.

Item Type: Article
DOI/Identification number: 10.1016/j.neurobiolaging.2018.02.013
Uncontrolled keywords: Aging, Circadian rhythm, NMDA, NR2B, Glutamate
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Gurprit Lall
Date Deposited: 15 Feb 2018 12:14 UTC
Last Modified: 29 May 2019 20:16 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/66030 (The current URI for this page, for reference purposes)
Lall, Gurprit S.: https://orcid.org/0000-0003-3725-4795
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