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夜间昏暗灯光对C57BL/6J小鼠脊髓损伤后恢复的影响。

Effects of dim light at night in C57BL/6J mice on recovery after spinal cord injury.

作者信息

Aldrich John C, Scheinfeld Ashley R, Lee Sydney E, Dusenbery Kalina J, Mahach Kathryn M, Van de Veire Brigid C, Fonken Laura K, Gaudet Andrew D

机构信息

Department of Psychology, College of Liberal Arts, The University of Texas at Austin.

Department of Neurology, Dell Medical School, The University of Texas at Austin.

出版信息

bioRxiv. 2024 Jan 9:2023.09.15.557980. doi: 10.1101/2023.09.15.557980.

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.

摘要

脊髓损伤(SCI)可导致长期的运动功能障碍、疼痛和情绪障碍。SCI后的炎症会加剧解剖和功能损伤,引发继发性损伤。SCI后一个有前景的治疗靶点是调控昼夜节律系统,该系统可根据一天中的不同时间优化生物学功能和行为,包括神经免疫反应和与情绪相关的行为。SCI后的昼夜节律紊乱可能因医院环境的干扰而加剧,医院环境通常包括夜间昏暗灯光(dLAN)。在此,我们假设,与饲养在昼夜分明环境(LD)中的小鼠相比,遭受SCI后置于dLAN环境中的小鼠会表现出更严重的运动功能障碍、疼痛样行为和焦虑抑郁样症状。C57BL/6J小鼠接受假手术或中度T9挫伤性SCI,然后永久性置于LD或dLAN环境中。SCI后的dLAN并未加重运动功能障碍;相反,SCI-dLAN小鼠在最后一个时间点的旷场运动表现出轻微改善。虽然dLAN未改变SCI诱导的热痛觉过敏,但与SCI-LD小鼠相比,SCI-dLAN小鼠在SCI后13天出现机械性异常性疼痛增加。使用蔗糖偏好试验(抑郁样)和旷场试验(焦虑样)时,SCI-LD和SCI-dLAN小鼠的结果相似。在术后21天,与SCI-LD小鼠相比,SCI-dLAN小鼠对新奇幼鼠的偏好降低,这意味着dLAN与SCI相结合可能会使这种与情绪相关的行为恶化。最后,SCI-LD和SCI-dLAN小鼠之间的损伤大小相似。因此,SCI后将C57BL/6J小鼠新置于dLAN环境中对运动、疼痛样和情绪相关行为有适度影响。未来的研究应考虑是否可以改善临床相关的昼夜节律干扰因素,单独或联合使用,以提高SCI后的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c7b/10786475/60e2fb442d17/nihpp-2023.09.15.557980v2-f0001.jpg

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