C57BL/6J mice exposed to dim light-at-night following a T9 contusion spinal cord injury exhibit modest improvements in locomotor recovery accompanied by increased behaviors related to depression and mechanical neuropathic pain
DOI:10.34945/F5N30H
DATASET CITATION
Aldrich J. C., Scheinfeld A. R., Lee S. E., Mahach K. M., Van de Veire B. C., Fonken L. K., Gaudet A. D. (2023) C57BL/6J mice exposed to dim light-at-night following a T9 contusion spinal cord injury exhibit modest improvements in locomotor recovery accompanied by increased behaviors related to depression and mechanical neuropathic pain. Open Data Commons for Spinal Cord Injury. ODC-SCI:956 http://doi.org/10.34945/F5N30H
ABSTRACT
STUDY PURPOSE: Nighttime disturbances are a common feature of extended hospital stays and likely lead to circadian disruption which, in turn, may exacerbate neuroinflammatory conditions. This study aimed to assess the effects of circadian disruption via exposure to dim light-at-night (dLAN) on locomotor recovery, tissue sparing, neuropathic pain sensitivity, and mood-related behaviors in mice following a T9 contusion spinal cord injury (SCI).
DATA COLLECTED: A more detailed methodology is available in the preprint: https://doi.org/10.1101/2023.09.15.557980. Briefly, male and female C57BL/6J mice were subjected to either moderate (65 kdyn) T9 contusion SCI or sham surgeries and subsequently housed under standard light-dark conditions (LD; 12 h light at 150 lux; 12 hr dark) or dLAN conditions (12 h light at 150 lux; 12 h dim light at 15 lux). The Basso mouse scale (BMS) was used to evaluate locomotor recovery at various timepoints from 1 to 35 days post-operation (dpo).
Heat hyperalgesia and mechanical allodynia were assessed using the Hargreaves test and the simplified up-down (SUDO) von Frey method, respectively, at 6 or 7 dpo and weekly thereafter. In both tests, left and right hindpaw scores are averaged together and for Hargreaves each hindpaw was tested three times.
Anxiety- and depressive-like behaviors were evaluated using the juvenile social exploration (JSE) test, sucrose preference test (SPT), and open-field test (OFT). JSE and OFT were performed prior to surgery and at 21 dpo while SPT was performed prior to surgery and at 14 and 29 dpo. For OFT and JSE, mouse behavior was tracked via Ethovision in an open area for 10 min followed by the introduction of a same-sex novel juvenile stimulus mouse (?4 weeks old) for 5 min. Distance traveled and percent time in the center 1/3rd of the arena for the first 5 min was recorded for OFT, while the amount of time spent interacting (e.g. sniffing, grooming, chasing, and fighting) with the juvenile was manually scored. For SPT, mice—housed alone or in sex-matched pairs, as noted in the dataset—were presented overnight with the choice of water or a 2% sucrose solution. Bottles containing water or sucrose were weighed before and after the test to determine the average amount consumed per mouse—i.e. in cases where two mice were housed together, the amount consumed was divided by two.
Finally, neuroprotection was assessed in 35 dpo spinal cord cryosections by measuring the lesion area and total cross-sectional area—based on anti-GFAP immunofluorescence staining of the astrocytic border—at 0.2 mm intervals surrounding the injury epicenter. Percent tissue sparing was calculated thusly: (total area – lesion area) / total area * 100%.
CONCLUSIONS: Subjecting C57BL/6J mice to SCI and housing them in dLAN had minimal effects on locomotor and pain-related outcomes. SCI mice exposed to dLAN displayed slightly improved locomotor function at 28 dpo—and no other timepoint—with an average BMS score of 6.25 vs. 5.05 for LD housed animals. Post-SCI dLAN exposure resulted in worsened mechanical hypersensitivity at 13 dpo—filament threshold 6.5 dLAN vs. 7.75 LD—and no difference in heat hypersensitivity. The impact of dLAN on mood-related behaviors in SCI mice was overall limited . No significant differences were observed in the sucrose preference and open-field tests between the two housing conditions—however, interestingly, SCI-dLAN mice exhibited a ~23% reduction in time spent on juvenile social exploration compared to SCI-LD mice, suggesting a potential increase in depressive-like behavior. Finally, consistent with the mild locomotor effect, we saw no difference in tissue sparing or lesion size in 35 dpo spinal cord sections. Overall, our findings indicate that C57BL/6J mice exposed to dim light-at-night following spinal cord injury displayed modest effects on locomotor recovery, pain-like responses, and mood-related behaviors. These results emphasize the need for future investigations to delve deeper into the impact of circadian disruption on post-injury outcomes, exploring a range of manipulations such as sleep fragmentation, stress, and varying lighting conditions, either individually or in combination, to better simulate more complex clinical scenarios.
KEYWORDS
Spinal Cord Injury; circadian rhythm; neuropathic pain; anxiety; depression; neuroinflammation; neuroprotection
PROVENANCE / ORIGINATING PUBLICATIONS
RELEVANT LINKS
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DATASET INFO
Contact: Gaudet Andrew (andrew.gaudet@utexas.edu)
Lab: Gaudet Lab | University of Texas at Austin
ODC-SCI Accession:956
Records in Dataset: 642
Fields per Record: 37
Last updated: 2023-10-17
Date published: 2023-10-17
Downloads: 4
Files: 2
LICENSE
Creative Commons Attribution License (CC-BY 4.0)
FUNDING AND ACKNOWLEDGEMENTS
University of Texas at Austin start-up funds (ADG), Wings for Life Foundation (ADG), TIRR Foundation Mission Connect (ADG), National Institute Of Neurological Disorders And Stroke of the National Institutes of Health R01NS131806 (ADG)
CONTRIBUTORS
- Aldrich, John C. [ORCID:0000-0002-4885-924X]
- 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
- Scheinfeld, Ashley R. [ORCID:0000-0002-5233-6142]
- 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
- Lee, Sydney E. [ORCID:0000-0002-1078-0149]
- 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
- Mahach, Kathryn M. [ORCID:0000-0002-5437-3764]
- 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
- Van de Veire, Brigid C. [ORCID:0009-0000-2439-3329]
- 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
- Fonken, Laura K. [ORCID:0000-0002-4705-9822]
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin
- Gaudet, Andrew D. [ORCID:0000-0001-8828-1553]
- 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
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