title: Aging-like circadian disturbances in folate-deficient mice.
abstract: The elderly population shows various circadian disturbances, including dampened amplitude of rhythmicity and decreased responsiveness to light. The common poor folate status in the elderly might account for these aging-related circadian disturbances. To test this hypothesis, we investigated whether folate deficiency in mice affects circadian oscillations of the master clock in the suprachiasmatic nuclei, and the shifting responses to light. Mice fed a diet without folate for 6 weeks displayed markedly reduced (4.5-fold) erythrocyte folate concentration and increased (2.3-fold) homocysteinemia compared with control mice. Folate deficiency decreased the circadian amplitude of vasopressin and the clock protein PERIOD 2 (PER2) in the master clock, slowed the rate of re-entrainment of behavioral rhythms after delayed light-dark cycle and reduced light-induced phase-delays, without detectable morphologic changes in the retina, such as the number of melanopsinergic ganglion cells, that might have impaired photodetection. In conclusion, folate deficiency and consecutive hyperhomocysteinemia led to dampened PER2 and vasopressin oscillations in the master clock and reduced responsiveness to photic resetting, which constitute hallmarks of aging effects on circadian rhythmicity.
authors.affiliation: Department of Neurobiology of Rhythms, Institute of Cellular and Integrative Neurosciences, CNRS UPR3212 associated with University of Strasbourg, Strasbourg, France. challet@inci-cnrs.unistra.fr
authors.forename: Etienne
authors.initials: E
authors.lastname: Challet
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dumont
authors.forename: Madah K M
authors.initials: MK
authors.lastname: Mehdi
authors.forename: Caroline
authors.initials: C
authors.lastname: Allemann
authors.forename: Tiffanie
authors.initials: T
authors.lastname: Bousser
authors.forename: Sylviane
authors.initials: S
authors.lastname: Gourmelen
authors.forename: Dominique
authors.initials: D
authors.lastname: Sage-Ciocca
authors.forename: David
authors.initials: D
authors.lastname: Hicks
authors.forename: Paul
authors.initials: P
authors.lastname: Pévet
authors.forename: Bruno
authors.initials: B
authors.lastname: Claustrat
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D005494:Folic Acid Deficiency / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D056950:Period Circadian Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism
chemical_list: C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D014667:Vasopressins