A Comprehensive Overview of the Neural Mechanisms of Light Therapy.

Light is a powerful environmental factor influencing diverse brain functions. Clinical evidence supports the beneficial effect of light therapy on several diseases, including depression, cognitive dysfunction, chronic pain, and sleep disorders. However, the precise mechanisms underlying the effects of light therapy are still not well understood. In this review, we critically evaluate current clinical evidence showing the beneficial effects of light therapy on diseases. In addition, we introduce the research progress regarding the neural circuit mechanisms underlying the modulatory effects of light on brain functions, including mood, memory, pain perception, sleep, circadian rhythm, brain development, and metabolism.

A visual circuit related to the habenula mediates the prevention of cocaine relapse by bright light treatment.

Despite significant advancements in our understanding of addiction at the neurobiological level, a highly effective extinction procedure for preventing relapse remains elusive. In this study, we report that bright light treatment (BLT) administered during cocaine withdrawal with extinction training prevents cocaine-driven reinstatement by acting through the thalamic-habenular pathway. We found that during cocaine withdrawal, the lateral habenula (LHb) was recruited, and inhibition of the LHb via BLT prevented cocaine-driven reinstatement. We also demonstrated that the effects of BLT were mediated by activating LHb-projecting neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL) or by inhibiting postsynaptic LHb neurons. Furthermore, BLT was found to improve aversive emotional states induced by drug withdrawal. Our findings suggest that BLT administered during the cocaine withdrawal may be a promising strategy for achieving drug abstinence.

Efficacy of light therapy for a college student sample with non-seasonal subthreshold depression: An RCT study.

BACKGROUND: Light therapy has been successfully used to treat seasonal and non-seasonal depression, but there is limited evidence for its efficacy in subthreshold depression. This study examines the efficacy of light therapy for symptoms of depression and anxiety in non-seasonal subthreshold depression. METHODS: College students with non-seasonal subthreshold depression were recruited. The participants were randomly allocated to one of the three conditions: high- (LT-5000 lux) and low-intensity (LT-500 lux) light therapy conditions and a waiting-list control condition (WLC). The primary outcome was Hamilton Depression Rating Scale (HAMD), and secondary outcomes were Beck Depression Inventory-II (BDI-II) and state anxiety inventory (SAI), which were assessed at baseline (Week 0), during the trial (Week 4), and after completion of the light therapy (Week 8). RESULTS: A total of 142 participants completed the trial. The LT-5000 (effect size [d] = 1.56, 95% CI: 1.15 to 1.98) and LT-500 conditions (d = 0.84, 95% CI: 0.43 to 1.26) were significantly superior to the WLC condition. For the LT-5000, LT-500, and WLC conditions by the end of the 8-week trial, a response on the HAMD was achieved by 70.0%, 42.0% and 19.0% of the participants, and remission was achieved by 76.0%, 54.0%, and 19.0%, respectively. LIMITATIONS: The subjects were not followed up regularly after completion of the trial. CONCLUSION: Light therapy, both at high- and low-intensity, was efficacious in the treatment of college students with non-seasonal subthreshold depression. High-intensity light therapy was superior to low-intensity light therapy by the end of an 8-week trial.

Pro-inflammatory cytokines serve as communicating molecules between the liver and brain for hepatic encephalopathy pathogenesis and Lycium barbarum polysaccharides protection.

ETHNOPHARMACOLOGICAL RELEVANCE: Gogi berry is a traditional food supplement and medical herbal which has been widely used in Eastern Asian countries. Lycium barbarum polysaccharides (LBP) are the major active components of Gogi berry and have been proved to possess a lot of biological activities. AIM OF THE STUDY: We aimed to delineate the protective effect and mechanism of LBP on hepatic encephalopathy (HE). MATERIALS AND METHODS: We investigated the protective mechanism of LBP in a thioacetamide (TAA, intraperitoneally injected, 400 mg/kg) induced acute HE mice model. Key phenotypes of clinical HE were phenocopied in the mice model, including high mortality, severe hepatic histology injury, increased hepatic oxidative stress, apoptosis, enhanced circulating levels of pro-inflammatory cytokines and ammonia, suppressed tryptophan hydroxylase activity, and deficits in locomotor activity. RESULTS: The pathological alterations were effectively ameliorated by the oral administration with LBP (5 mg/kg, oral gavage, everyday), which were mediated by regulating MAPK pathways in both the liver and brain. Knockout of pro-inflammatory cytokines TNF-α or IL-6 effectively ameliorated impaired mice locomotor activity and MAPK activation in the brain. In an in vitro TNF-α-, IL-6-, or ammonia-induced microglia damaged cell model, cell injuries were evidently protected by the co-administration with LBP (50 µg/ml). CONCLUSION: LBP ameliorated the hepatic/brain injuries and impaired locomotor activities in a HE mice model. Pro-inflammatory cytokines may serve as communicating molecules linking the liver and brain for the HE pathogenesis, partly through MAPK regulation.

A Visual Circuit Related to Habenula Underlies the Antidepressive Effects of Light Therapy.

Light plays a pivotal role in the regulation of affective behaviors. However, the precise circuits that mediate the impact of light on depressive-like behaviors are not well understood. Here, we show that light influences depressive-like behaviors through a disynaptic circuit linking the retina and the lateral habenula (LHb). Specifically, M4-type melanopsin-expressing retinal ganglion cells (RGCs) innervate GABA neurons in the thalamic ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which in turn inhibit CaMKIIα neurons in the LHb. Specific activation of vLGN/IGL-projecting RGCs, activation of LHb-projecting vLGN/IGL neurons, or inhibition of postsynaptic LHb neurons is sufficient to decrease the depressive-like behaviors evoked by long-term exposure to aversive stimuli or chronic social defeat stress. Furthermore, we demonstrate that the antidepressive effects of light therapy require activation of the retina-vLGN/IGL-LHb pathway. These results reveal a dedicated retina-vLGN/IGL-LHb circuit that regulates depressive-like behaviors and provide a potential mechanistic explanation for light treatment of depression.

A retinoraphe projection regulates serotonergic activity and looming-evoked defensive behaviour.

Animals promote their survival by avoiding rapidly approaching objects that indicate threats. In mice, looming-evoked defensive responses are triggered by the superior colliculus (SC) which receives direct retinal inputs. However, the specific neural circuits that begin in the retina and mediate this important behaviour remain unclear. Here we identify a subset of retinal ganglion cells (RGCs) that controls mouse looming-evoked defensive responses through axonal collaterals to the dorsal raphe nucleus (DRN) and SC. Looming signals transmitted by DRN-projecting RGCs activate DRN GABAergic neurons that in turn inhibit serotoninergic neurons. Moreover, activation of DRN serotoninergic neurons reduces looming-evoked defensive behaviours. Thus, a dedicated population of RGCs signals rapidly approaching visual threats and their input to the DRN controls a serotonergic self-gating mechanism that regulates innate defensive responses. Our study provides new insights into how the DRN and SC work in concert to extract and translate visual threats into defensive behavioural responses.

Lycium barbarum polysaccharide improves bipolar pulse current-induced microglia cell injury through modulating autophagy.

Blindness and visual impairments are heavy loads for modern society. Visual prosthesis is a promising therapy to treat these diseases. However, electric stimulation (ES)-induced damage of the optic nerve and adjacent cells are problems that must not be overlooked. In the current study, we aimed to investigate the effects of ES on cultured microglia cells and the potential protective mechanisms from a natural compound Lycium barbarum polysaccharide (LBP). Cellular injuries were induced by 9 mA bipolar pulse current in BV-2 cells for 15 min. Treatment with LBP alone or in association with either autophagic inhibitor 3-MA or autophagic agonist rapamycin was preadded for 2 h before the ES challenge. After that, morphological and molecular changes of the cells were measured at 2 h or 6 h postchallenges. We found that ES induced evident morphological and pathological changes of BV-2 cells, including oxidative stress, inflammation, and apoptosis. Pretreatment with LBP significantly attenuated these injuries with enhanced endogenous autophagy. When cellular autophagy was inhibited or enhanced by corresponding drug, the protective properties of LBP were partly inhibited or maintained, respectively. In addition, we demonstrated that ERK and p38 MAPK exerted diversified roles in the protection of LBP against ES-induced cellular damages. In conclusion, LBP improves bipolar pulse current-induced microglia cell injury through modulating autophagy and MAPK pathway.