Elsevier

Neurobiology of Aging

Volume 66, June 2018, Pages 75-84
Neurobiology of Aging

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

https://doi.org/10.1016/j.neurobiolaging.2018.02.013Get rights and content
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open access

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.

Keywords

Aging
Circadian rhythm
NMDA
NR2B
Glutamate

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