title: Disruption of circadian clocks has ramifications for metabolism, brain, and behavior.
abstract: Circadian (daily) rhythms are present in almost all plants and animals. In mammals, a brain clock located in the hypothalamic suprachiasmatic nucleus maintains synchrony between environmental light/dark cycles and physiology and behavior. Over the past 100 y, especially with the advent of electric lighting, modern society has resulted in a round-the-clock lifestyle, in which natural connections between rest/activity cycles and environmental light/dark cycles have been degraded or even broken. Instances in which rapid changes to sleep patterns are necessary, such as transmeridian air travel, demonstrate negative effects of acute circadian disruption on physiology and behavior. However, the ramifications of chronic disruption of the circadian clock for mental and physical health are not yet fully understood. By housing mice in 20-h light/dark cycles, incongruous with their endogenous ∼24-h circadian period, we were able to model the effects of chronic circadian disruption noninvasively. Housing in these conditions results in accelerated weight gain and obesity, as well as changes in metabolic hormones. In the brain, circadian-disrupted mice exhibit a loss of dendritic length and decreased complexity of neurons in the prelimbic prefrontal cortex, a brain region important in executive function and emotional control. Disrupted animals show decreases in cognitive flexibility and changes in emotionality consistent with the changes seen in neural architecture. How our findings translate to humans living and working in chronic circadian disruption is unknown, but we believe that this model can provide a foundation to understand how environmental disruption of circadian rhythms impacts the brain, behavior, and physiology.
authors.affiliation: Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065, USA. ikaratsore@rockefeller.edu
authors.forename: Ilia N
authors.initials: IN
authors.lastname: Karatsoreos
authors.forename: Sarah
authors.initials: S
authors.lastname: Bhagat
authors.forename: Erik B
authors.initials: EB
authors.lastname: Bloss
authors.forename: John H
authors.initials: JH
authors.lastname: Morrison
authors.forename: Bruce S
authors.initials: BS
authors.lastname: McEwen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001683:Biological Clocks / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001831:Body Temperature / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000502:physiology*; D057906:Circadian Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000502:physiology; D017440:Photoperiod; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology; D015430:Weight Gain / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin