Effects of bright light therapy on neuroinflammatory and neuroplasticity markers in a diurnal rodent model of Seasonal Affective Disorder.

BACKGROUND: Bright light therapy (BLT) is widely used for treating Seasonal Affective Disorder (SAD). However, the neural mechanisms underlying the therapeutic effects of BLT remain largely unexplored. The present study used a diurnal rodent (Nile grass rats; Arvicanthis niloticus) to test the hypothesis that the therapeutic effects of BLT could be, in part, due to reduced neuroinflammation and/or enhanced neuroplasticity. Our previous research has demonstrated that compared to grass rats housed in a summer-like daytime bright light condition (1000 lux), those housed in a winter-like daytime dim light condition (50 lux) showed increased depression- and anxiety-like behaviours, as well as impaired sociosexual behaviours and spatial memory, similar to what is observed in patients suffering from SAD. MATERIALS AND METHODS: In the present study, male and female grass rats were housed under the winter-like dim daytime light condition (lights on 600-1800 hr, 50 lux). The experimental groups received daily 1-h early morning BLT from 0600-0700 using full-spectrum light (10,000 lux), while the control groups received narrowband red light (λmax, 780 nm). Following 4 weeks of treatment, the expression of several neuroinflammatory or plasticity markers was examined in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and the CA1 of the dorsal hippocampus. RESULTS: For the neuroinflammatory markers, BLT reduced TNF-α in the BLA of females, and upregulated CD11b in the mPFC and IL6 in the BLA in males. For the neuroplasticity markers, BLT downregulated BDNF in the CA1 and TrkB in all three brain regions in females but upregulated BDNF in the BLA and CA1 in males. CONCLUSIONS: These results indicate that the therapeutic effects of BLT on sleep, mood, and cognition may be attributed in part to mechanisms involving neuroinflammation and neuroplasticity in corticolimbic brain regions. Moreover, these effects appear to vary between sexes.

Effects of light therapy on sleep/wakefulness, daily rhythms, and the central orexin system in a diurnal rodent model of seasonal affective disorder.

BACKGROUND: Bright light therapy (BLT) is the first-line treatment for seasonal affective disorder. However, the neural mechanisms underlying BLT are unclear. To begin filling this gap, the present study examined the impact of BLT on sleep/wakefulness, daily rhythms, and the wakefulness-promoting orexin/hypocretin system in a diurnal rodent, Nile grass rats (Arvicanthis niloticus). METHODS: Male and female grass rats were housed under a 12:12 h light/dark cycle with dim light (50 lx) during the day. The experimental group received daily 1-h early morning BLT (full-spectrum white light, 10,000 lx), while the control group received narrowband red light for 4 weeks. Sleep/wakefulness and in-cage locomotor activity were monitored, followed by examination of hypothalamic prepro-orexin and orexin receptors OX1R and OX2R expression in corticolimbic brain regions. RESULTS: The BLT group had higher wakefulness during light treatment, better nighttime sleep quality, and improved daily rhythm entrainment compared to controls. The impact of BLT on the orexin system was sex- and brain region-specific, with males showing higher OX1R and OX2R in the CA1, while females showed higher prepro-orexin but lower OX1R and OX2R in the BLA, compared to same-sex controls. LIMITATIONS: The present study focused on the orexin system in a limited number of brain regions at a single time point. Sex wasn't a statistical factor, as male and female cohorts were run independently. CONCLUSIONS: The diurnal grass rats show similar behavioral responses to BLT as humans, thus could be a good model for further elucidating the neural mechanisms underlying the therapeutic effects of BLT.

Daytime Light Deficiency Leads to Sex- and Brain Region-Specific Neuroinflammatory Responses in a Diurnal Rodent.

Seasonal changes in peripheral inflammation are well documented in both humans and animal models, but seasonal changes in neuroinflammation, especially the impact of seasonal lighting environment on neuroinflammation remain unclear. To address this question, the present study examined the effects of environmental lighting conditions on neuroinflammation in a diurnal rodent model, Nile grass rats (Arvicanthis niloticus). Male and female grass rats were housed in either bright (brLD) or dim (dimLD) light during the day to simulate a summer or winter light condition, respectively. After 4 weeks, microglia markers Iba-1 and CD11b, as well as pro-inflammatory cytokines TNF-α and IL-6, were examined in the anterior cingulate cortex (ACC), basolateral amygdala (BLA), and dorsal hippocampus (dHipp). The results revealed that winter-like dim light during the day leads to indicators of increased neuroinflammation in a brain site- and sex-specific manner. Specifically, relatively few changes in the neuroinflammatory markers were observed in the ACC, while numerous changes were found in the BLA and dHipp. In the BLA, winter-like dimLD resulted in hyper-ramified microglia morphology and increased expression of the pro-inflammatory cytokine IL-6, but only in males. In the dHipp, dimLD led to a higher number and hyper-ramified morphology of microglia as well as increased expression of CD11b and TNF-α, but only in females. Neuroinflammatory state is thus influenced by environmental light, differently in males and females, and could play a role in sex differences in the prevalence and symptoms of psychiatric or neurological disorders that are influenced by season or other environmental light conditions. Diurnal Nile grass rats were housed under bright or dim light during the day for 4 weeks, simulating seasonal fluctuations in daytime lighting environment. Dim light housing resulted in hyper-ramified morphology of microglia (scale bar, 15 µm) and altered expression of pro-inflammatory cytokines (TNF-α) in a sex- and brain region-specific manner.