No 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.

Abstract:The field of chronobiology has vastly expanded over the past few decades, bringing together research from the fields of circadian rhythms and sleep. The importance of the environmental day-night cycle on our health is becoming increasingly evident as we evolve into a 24-hour society. Reducing or changing sleep times against our natural instincts to rest at night has a detrimental impact on our well-being. The mammalian circadian clock, termed "the suprachiasmatic nucleus", is responsible for synchronizing our behavioral and physiological outputs to the environment. It utilizes light transcoded by specialized retinal photoreceptors as its cue to set internal rhythms to be in phase with the light-dark cycle. Misalignment of these outputs results in symptoms such as altered/disturbed sleep patterns, changes in mood, and physical and mental exhaustion -symptoms shared by many affective clinical disorders. Key links to circadian abnormalities have been found in a number of disorders, such as seasonal affective disorder, nonseasonal depression, and bipolar affective disorder. Furthermore, therapies developed through chronobiological research have been shown to be beneficial in the treatment of these conditions. In this article, we discuss the impact of circadian research on the management of affective disorders, giving evidence of how a misaligned circadian system may be a contributor to the symptoms of depression and how moderating circadian rhythms with light therapy benefits patients.