RT Journal Article
SR Electronic
T1 Spinal Cord Injury in Rats Disrupts the Circadian System
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0328-18.2018
DO 10.1523/ENEURO.0328-18.2018
VO 5
IS 6
A1 Andrew D. Gaudet
A1 Laura K. Fonken
A1 Monica T. Ayala
A1 Emily M. Bateman
A1 Wolfgang E. Schleicher
A1 Elana J. Smith
A1 Heather M. D’Angelo
A1 Steven F. Maier
A1 Linda R. Watkins
YR 2018
UL http://www.eneuro.org/content/5/6/ENEURO.0328-18.2018.abstract
AB Spinal cord injury (SCI) perturbs many physiological systems. The circadian system helps maintain homeostasis throughout the body by synchronizing physiological and behavioral functions to predictable daily events. Whether disruption of these coordinated daily rhythms contributes to SCI-associated pathology remains understudied. Here, we hypothesized that SCI in rats would dysregulate several prominent circadian outputs including glucocorticoids, core temperature, activity, neuroinflammation, and circadian gene networks. Female and male Sprague Dawley rats were subjected to clinically relevant thoracic 9 moderate contusion SCI (or laminectomy sham surgery). Diurnal measures—including rhythms of plasma corticosterone (CORT), body temperature, and activity (using small implanted transmitters), and intraspinal circadian and inflammatory gene expression—were studied prior to and after surgery. SCI caused overall increases and disrupted rhythms of the major rodent glucocorticoid, CORT. Presurgery and sham rats displayed expected rhythms in body temperature and activity, whereas rats with SCI had blunted daily rhythms in body temperature and activity. In parallel, SCI disrupted intraspinal rhythms of circadian clock gene expression. Circadian clock genes can act as transcriptional regulators of inflammatory pathways. Indeed, SCI rats also showed dysregulated rhythms in inflammatory gene expression in both the epicenter and distal spinal cord. Our data show that moderate SCI in rats causes wide-ranging diurnal rhythm dysfunction, which is severe at acute time points and gradually recovers over time. Normalizing post-SCI diurnal rhythms could enhance the recovery of homeostasis and quality of life.