| Background and Objective:Depression is a disease characterized by anhedonia,low mood,and pessimism.According to the World Health Organization,there are currently 350 million people suffering from depression worldwide.However,the largest clinical study of antidepressants to date suggests that only 67% of patients who use 4 antidepressants consecutively have a clinical cure rate.Non-drug treatment has become an important methods.In recent years,many studies have shown that light therapy can effectively improve depressive symptoms,and has the advantages of quick onset,few side effects,and convenient operation.There are various types of light sources used clinically.Different lighting parameter combinations have different therapeutic effects on depression.Due to the low illumination of narrow-band blue light(455-500nm)and its more obvious role in regulating biological rhythms,research on blue light has gradually increased in recent years.Therefore,this study uses blue light sources with different parameters to explore the differences in the effects of phototherapy on depression.Lateral habenular(lateral habenular,LHb),Hippocampus(Hippocampus,Hip),medial prefrontal cortex(medial prefrontal cortex,mPFC)and other brain regions play an important role in the occurrence of depression,and also play an important role in the antidepressant effect of light therapy.However,the specific effects of blue light with different parameters on these brain areas are still unknown.Therefore,the purpose of this study is to explore whether blue light can prevent the occurrence of depression and whether it can treat depressionlike phenotypes;to determine the optimal number of days of light,the optimal length of daily light and the optimal frequency of light,so as to screen out the antidepressant effect Optimum blue light illumination parameters;explore the potential neural mechanism of blue light illumination improving depression from different levels such as behavior,tissue,and cell.Methods:In this study,male C57/BL mice were used as the research object,using corticosterone injection combined with chronic restraint depression model(Corticosterone-Chronic Restraint Stress,Cort-Crs),through behavioral experiments immunofluorescence staining,in vivo calcium imaging and other methods to explore the effects and possibilities of different blue light phototherapy programs(lighting days,daily light duration,light frequency)on depression-like behaviors of depressed mice Mechanism.Results:1.The preventive effect of different light parameters on the occurrence of depression-like phenotype in mice.1.1 Effects of different photoperiods on the occurrence of depression-like behavior in mice:Use 40 Hz,3h blue light illumination mode per day.After modeling,the body weight of the Cort-Crs group decreased significantly(p< 0.0001);after blue light irradiation,the weight of the Light-2w(p< 0.01),Light-3w,and Light-4w groups all increased significantly(p< 0.001).In the sugar water preference experiment,the sugar water preference value of the Cort-Crs group was significantly lower than that of the Con group(p<0.05);the sugar water preference value of the Light-3w group was significantly higher than that of the Cort-Crs group(p< 0.05);in the tail suspension test,compared with the Con group,the immobility time of the Cort-Crs group was significantly increased(p<0.01).There was a significant difference(p< 0.01)in the reduction of immobility time between the Light-3w group and the Light-4w group.From the above results,the best period for blue light phototherapy to prevent the occurrence of depression-like phenotype in mice is 3 weeks.1.2.Effects of different daily light durations on the occurrence of depression-like behaviors in mice:Use a 40 Hz,blue light exposure pattern for 3 weeks.After modeling,the body weight of the Cort-Crs group decreased significantly(p< 0.0001).The body weight of Light-2h group,Light-3h group and Light-4h group all increased,but there was no statistical difference(p> 0.05).In the sugar water preference experiment,the sugar water preference value of the Cort-Crs group decreased significantly(p< 0.05);the sugar water preference value of the Light-3h group and Light-4h group increased significantly(p<0.05).In the tail suspension test,the immobility time of the Cort-Crs group was significantly increased(p< 0.05);the immobility time of the three light groups were all significantly decreased(p< 0.05).From the above results,the best daily light duration for blue light phototherapy to prevent depression-like phenotype in mice is 3 hours.1.3 Effects of different frequencies of light on the occurrence of depression-like behaviors in mice:A light pattern of 40 Hz,3 week,3 hours of blue light exposure per day was used.After modeling,the body weight of the Cort-Crs group decreased significantly(p< 0.001).Light-0Hz,Light-8Hz,and Light-40 Hz light groups all increased body weight,but there was no statistical difference(p> 0.05).In the sugar water preference experiment,the sugar water preference value of the Cort-Crs group decreased significantly(p<0.05);the sugar water preference value of the Light-0Hz group and the Light-40 Hz group increased significantly(p<0.05).In the tail suspension test,the immobility time of the Cort-Crs group was significantly increased(p<0.05);the immobility time of the three light groups were all significantly decreased(p<0.01).In summary,using a narrow-spectrum blue light source,a light cycle of 3 weeks,a daily light duration of 3 hours,and a light frequency of 8 Hz or 40 Hz has the best preventive effect on the occurrence of depression-like phenotypes in mice.2.The therapeutic effect of different light parameters on Cort-Crs depression model mice:Use 40 Hz blue light with an optimal photoperiod of 3 weeks and a daily photoperiod of 3 hours.After modeling,the body weight of the mice in the Cort-Crs group was significantly lower than that in the Con group(p<0.05).The body weight of the blue light group increased significantly(p<0.05);in the sugar water preference experiment,the sugar water preference value of the Cort-Crs group decreased significantly(p<0.05);the sugar water preference value of the Light-8Hz group increased significantly(p<0.05).In the forced swimming test,the immobility time of the mice in the Cort-Crs group was significantly prolonged(p<0.05);the immobility time of the Light-8Hz group and the Light-40 Hz group was significantly reduced(p<0.05).To sum up,by comparing the treatment differences of different light parameters,it is found that the best light frequency is 8Hz or 40 Hz.3.Immunofluorescence staining results:In the phototherapy experiment,compared with the Con group,the expression of cFos in LHb,Hip,Pir,PFC,and brain regions related to depression in the Cort-Crs group was significantly increased,and the expression of c-Fos in these brain regions was significantly increased after phototherapy.In the light prevention depression experiment,compared with the Con group,the expression of c-Fos in the LHb and BNST brain regions of the Cort-Crs group increased significantly,but the c-Fos expression There was no significant difference in expression.4.In vivo calcium imaging results:The results of in vivo calcium imaging showed that the activity of neurons in the LHb brain area significantly increased when the mice received negative stimulation;however,when the mice were irradiated with 40 Hz blue light while receiving negative stimulation,the activity of neurons in the LHb brain area decreased significantly.Conclusion:The above experiments prove that blue light irradiation has certain effects on the occurrence,development and treatment of depression.Among them,the light source parameter selection is 8Hz or 40 Hz,3 hours a day,and the total intervention period is 3weeks.The prevention/treatment effect is the best.The mechanism of blue light phototherapy to relieve depressive symptoms may be related to the regulation of abnormal activity of neurons in important depression-related brain regions such as LHb,Hip,and PFC. |
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