Date Published: December 1, 2010
Publisher: Public Library of Science
Author(s): Erin M. Gibson, Connie Wang, Stephanie Tjho, Neera Khattar, Lance J. Kriegsfeld, Shin Yamazaki. http://doi.org/10.1371/journal.pone.0015267
Abstract: Circadian disruptions through frequent transmeridian travel, rotating shift work, and poor sleep hygiene are associated with an array of physical and mental health maladies, including marked deficits in human cognitive function. Despite anecdotal and correlational reports suggesting a negative impact of circadian disruptions on brain function, this possibility has not been experimentally examined.
In the present study, we investigated whether experimental ‘jet lag’ (i.e., phase advances of the light∶dark cycle) negatively impacts learning and memory and whether any deficits observed are associated with reductions in hippocampal cell proliferation and neurogenesis. Because insults to circadian timing alter circulating glucocorticoid and sex steroid concentrations, both of which influence neurogenesis and learning/memory, we assessed the contribution of these endocrine factors to any observed alterations. Circadian disruption resulted in pronounced deficits in learning and memory paralleled by marked reductions in hippocampal cell proliferation and neurogenesis. Significantly, deficits in hippocampal-dependent learning and memory were not only seen during the period of the circadian disruption, but also persisted well after the cessation of jet lag, suggesting long-lasting negative consequences on brain function.
Together, these findings support the view that circadian disruptions suppress hippocampal neurogenesis via a glucocorticoid-independent mechanism, imposing pronounced and persistent impairments on learning and memory.
Partial Text: Frequent transmeridian travel, rotating shift work schedules, and irregular sleep patterns result in an incongruence between the endogenous circadian timing system and the external environment , , , . This loss of synchrony is associated with a number of clinical pathologies, including a higher incidence of cancer , , diabetes , hypertension and cardiovascular disease , , reduced fertility and fecundity , , and an exacerbation in a number of pre-existing psychological pathologies ,  relative to individuals with consistent schedules. Most relevant to the present series of studies, several lines of investigation using human and animal models suggest a pronounced influence of circadian timekeeping on learning and memory , , , .
The present findings show, for the first time, that circadian disruptions lead to marked suppression of hippocampal cell proliferation and neurogenesis, associated with notable deficits in learning and memory. Adrenalectomy abolished the effects of jet lag on cell proliferation, suggesting that circadian disruptions impact this measure, in part, via HPA axis activation. In contrast, the pronounced suppression of neurogenesis is independent of jet lag-induced alterations in circulating glucocorticoid and sex steroid concentrations. Jet-lagged animals exhibited ∼24-hr rhythms, not synchronized with external time, suggesting that the observed deficits result from a desynchrony between internal physiology and external time, not from gross disruptions in internal rhythmicity. Additionally, the duration and amplitude of the activity/rest cycle was not impacted by the treatment, suggesting that the results are not a consequence of sleep deprivation as has been shown previously , . Together, these results underscore the importance of circadian entrainment in maintaining optimal neural and cognitive functioning.