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

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.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Biello SM,Bonsall DR,Atkinson LA,Molyneux PC,Harrington ME,Lall GS

doi

10.1016/j.neurobiolaging.2018.02.013

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

75-84

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(18)30056-3

journal_volume

66

pub_type

杂志文章

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