Alterations in glutamatergic signaling contribute to the decline of circadian photoentrainment in aged mice
| Autor: | Lynsey A Atkinson, Gurprit S. Lall, David R. Bonsall, Penny C. Molyneux, Mary E. Harrington, Stephany M. Biello |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Agonist Aging N-Methylaspartate Light medicine.drug_class Biology Chronobiology Disorders Eye Article RS 03 medical and health sciences Glutamatergic 0302 clinical medicine medicine Animals Visual Pathways Circadian rhythm Receptor Suprachiasmatic nucleus musculoskeletal neural and ocular physiology General Neuroscience Glutamate receptor Circadian Rhythm Mice Inbred C57BL 030104 developmental biology nervous system NMDA receptor Suprachiasmatic Nucleus Neurology (clinical) Geriatrics and Gerontology Entrainment (chronobiology) Neuroscience 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
| Zdroj: | Neurobiology of Aging. 66:75-84 |
| ISSN: | 0197-4580 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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