Our new paper has been accepted for publication at Experimental Neurology! Congrats to co-first authors Dr. John Aldrich and Ashley Scheinfeld, and the rest of our team. In this manuscript, we sought to determine whether dim light-at-night (dLAN) after spinal cord injury (SCI) alters locomotor recovery, pain- or mood-related behaviors, or neuroprotection.
Our new manuscript is available at Experimental Neurology; the article is accessible on BioRxiv; and its dataset is on Open Data Commons repository.
Our prior work established that SCI disrupts the circadian system, including glucocorticoid rhythms, core temperature and activity rhythms, and rhythms of clock and inflammatory gene RNA in the spinal cord and liver. Others revealed that clinically relevant environmental circadian disruptors – such as dLAN – can exacerbate secondary damage and recovery in neurological conditions, such as global ischemia.
In our manuscript, we hypothesized that dLAN initiated after SCI would worsen functional and anatomical deficits. Adult female and male mice were subjected to SCI (or sham surgery), then placed back in light-dark (LD) cycles or newly placed in dLAN (12 h light; 12 h dim 15 lux light). This was designed to mimic the hospital setting, which often has unnaturally high nighttime light levels.
Fig. 1. Effects of dim light-at-night (dLAN) after SCI on locomotor recovery (Basso Mouse Scale; a), mechanical pain symptoms (von Frey test; b), and juvenile exploration (mood-related behavior; c). SCI-dLAN (vs. SCI-LD) mice showed improved BMS at 28 dpo, worsened mechanical hypersensitivity at 13 dpo, and worse anxiety- and/or depressive-like behavior at 21 dpo. p<0.05: red cross = sham vs. SCI; hourglass = effect of time; lightbulb = LD vs. dLAN.
Our results showed that dLAN had modest effects on behavioral outcomes. Locomotor recovery was assessed using the open-field Basso Mouse Scale (BMS). dLAN had little effect on locomotor recovery after SCI, except at the final timepoint, when SCI-dLAN mice had increased function compared to SCI-LD mice (Fig. 1a above). Lesion size and neuroprotection were not significantly different between SCI-LD compared to SCI-dLAN mice. Neuropathic pain-like behavior was assessed using the Hargreaves test (heat) and the von Frey test (mechanical). Whereas dLAN did not modulate sensitivity to heat (not shown), SCI-dLAN mice showed worsened mechanical hypersensitivity at 13 dpo only compared to SCI-LD mice (Fig. 1b). Mood-related behaviors were assessed using the sucrose preference test, open field test, and juvenile social exploration. dLAN had no significant effect on sucrose anhedonia or open field behavior (not shown). Interestingly, SCI-dLAN mice had decreased juvenile social exploration at 21 dpo compared to SCI-LD mice (Fig. 1c), suggestive of worsened anxiety- and/or depressive-like behavior.
Overall, our data suggest that dLAN has mixed effects on behavioral recovery after SCI - compared to SCI-LD mice, SCI-dLAN mice had slightly improved locomotor recovery at 28 dpo, worsened mechanical hypersensitivity at 13 dpo, and heightened anxiety-like behavior at 21 dpo. Future studies should explore whether SCI recovery is impaired by other clinically relevant circadian disruptors – e.g., LAN in a melatonin-expressing strain, sleep deprivation, or combining disruptors. Ultimately, studying circadian disruption after SCI in mice will help define whether improving circadian hygiene in acute clinical care could benefit SCI recovery.