Abstract # 3188 Spinal cord injury perturbs circadian rhythms

Abstract

Spinal cord injury (SCI) can disrupt many physiological functions. The circadian system helps maintain homeostasis throughout the body by regulating daily rhythms in physiology and behavior. Circadian rhythms likely exist in all cell throughout the body, yet whether SCI alters daily rhythms remains under-studied. Here, we hypothesized that SCI in rats would disrupt several prominent circadian outputs including glucocorticoids, core temperature, activity, and circadian/inflammatory gene expression. Female and male rats received clinically relevant thoracic (T-) 8 moderate-to-severe contusion SCI (or laminectomy sham surgery). Circadian measures – including rhythms of plasma corticosterone, body temperature and activity (using small implanted transmitters), plasma glucose, and gene expression – were studied before and after surgery. First, we found that SCI disrupted intraspinal and peripheral rhythms of clock and inflammatory gene expression. Circadian rhythms in peripheral cells are entrained by “oscillatory factors”, including glucocorticoids, body temperature, and activity. SCI increased and disrupted rhythms of the major rodent glucocorticoid, corticosterone. Pre-surgery and sham rats displayed expected rhythms in activity and body temperature, whereas SCI rats had blunted daily rhythms in activity and body temperature. In parallel, SCI increased plasma glucose and liver expression of glucose metabolism genes. Our data show that moderate SCI in rats causes wide-ranging circadian dysfunction that is severe at acute time points and gradually recovers. Normalizing post-SCI circadian rhythms could enhance recovery of homeostasis and quality-of-life.