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bioRxiv · 10.1101/2023.09.15.557980

Effects of circadian disruption via dim light at night in C57BL6/J mice on recoveryafter spinal cord injury

Aldrich, J. C.·Scheinfeld, A. R.·Lee, S. E.·Mahach, K. M.·Van de Veire, B. C.·Fonken, L. K.·Gaudet, A. D.
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Abstract

Spinal cord injury (SCI) can cause long-lasting locomotor deficits, pain, and mood disorders. Anatomical and functional outcomes are exacerbated by inflammation after SCI, which causes secondary damage. One promising target after SCI is manipulating the circadian system, which optimizes biology and behavior for time of day - including neuroimmune responses and mood- related behaviors. Circadian disruption after SCI is likely worsened by a disruptive hospital environment, which typically includes dim light-at-night (dLAN). Here, we hypothesized that mice subjected to SCI, then placed in dLAN, would exhibit worsened locomotor deficits, pain- like behavior, and anxiety-depressive-like symptoms compared to mice maintained in light days with dark nights (LD). C57BL/6J mice received sham surgery or moderate T9 contusion SCI, then were placed permanently in LD or dLAN. dLAN after SCI did not worsen locomotor deficits; rather, SCI-dLAN mice showed slight improvement in open-field locomotion at the final timepoint. Although dLAN did not alter SCI-induced heat hyperalgesia, SCI-dLAN mice exhibited an increase in mechanical allodynia at 13 days post-SCI compared to SCI-LD mice. SCI-LD and SCI-dLAN mice had similar outcomes using sucrose preference (depressive-like) and open-field (anxiety-like) tests. At 21 dpo, SCI-dLAN mice had reduced preference for a novel juvenile compared to SCI-LD, implying that dLAN combined with SCI may worsen this mood-related behavior. Finally, lesion size was similar between SCI-LD and SCI-dLAN mice. Therefore, newly placing C57BL/6J mice in dLAN after SCI had modest effects on locomotor, pain-like, and mood-related behaviors. Future studies should consider whether clinically-relevant circadian disruptors, alone or in combination, could be ameliorated to enhance outcomes after SCI.

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Aldrich, J. C., Scheinfeld, A. R., Lee, S. E., Mahach, K. M., Van de Veire, B. C., Fonken, L. K., Gaudet, A. D.. 2023-09-16. Effects of circadian disruption via dim light at night in C57BL6/J mice on recoveryafter spinal cord injury. https://doi.org/10.1101/2023.09.15.557980

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