Biello, Stephany M., Bonsall, David R., Atkinson, Lynsey A., Molyneux, Penny C., Harrington, Mary E. and Lall, Gurprit S. (2018) Alterations in glutamatergic signaling contribute to the decline of circadian photoentrainment in aged mice. Neurobiology of Aging, 66. pp. 75-84. ISSN 0197-4580 (Print), 1558-1497 (Online) (doi:https://doi.org/10.1016/j.neurobiolaging.2018.02.013)

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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 (1e2 months) and old (14e18 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:	Article
Uncontrolled Keywords:	Aging, Circadian rhythm, NMDA, NR2B, Glutamate
Subjects:	R Medicine > RS Pharmacy and materia medica
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > Medway School of Pharmacy
Last Modified:	21 May 2018 08:40
URI:	http://gala.gre.ac.uk/id/eprint/19730

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