Spinal Cord Injury in Rats Disrupts the Circadian System
| Autor: | Linda R. Watkins, Monica T. Ayala, Wolfgang E. Schleicher, Andrew D. Gaudet, Laura K. Fonken, Elana J. Smith, Emily M. Bateman, Heather M. D'Angelo, Steven F. Maier |
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| Rok vydání: | 2018 |
| Předmět: |
Male
medicine.medical_specialty neurotrauma Motor Disorders Circadian clock CLOCK Proteins biological clock Chronobiology Disorders Statistics Nonparametric Rats Sprague-Dawley Rhythm Internal medicine Animals Medicine Circadian rhythm Spinal cord injury diurnal rhythms Spinal Cord Injuries Neuroinflammation Analysis of Variance Sex Characteristics business.industry General Neuroscience Body Weight 3.1 Arrhythmias Cardiac General Medicine New Research medicine.disease Spinal cord spinal cord injury Circadian Rhythm Rats Disease Models Animal medicine.anatomical_structure Endocrinology Gene Expression Regulation circadian rhythms Cytokines Disorders of the Nervous System Female Corticosterone business Locomotion Glucocorticoid Homeostasis medicine.drug |
| Zdroj: | eNeuro |
| ISSN: | 2373-2822 |
| DOI: | 10.1523/eneuro.0328-18.2018 |
| Popis: | Visual Abstract 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. |
| Databáze: | OpenAIRE |
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