Effect And Underlying Mechanism Of Specifically Down Regulating Per2 In Olfactory Bulb On Rat Depression-like Behaviors

Many studies have shown that the abnormality of circadian rhythm playing an important role in the development of depression.The research on the neurobiological mechanism of the causal relationship between circadian rhythm disturbances and depression attracts a lot of attention.Many studies have reported that activity of central neurons in some brain regions associate with depression and these neurons activity have the characteristics of circadian rhythm,involved in the regulation of the body’s circadian rhythms.However,we know little about the circadian rhythm of these brain regions and circadian rhythm mechanism in the pathogenesis of depression? Thus,understanding the role of these brain regions in the pathogenesis of depression from the perspective of circadian rhythm will provide a new explanation for the pathogenesis of depression.Removed the olfactory bulb(OB)can envoke the depressive symptoms in rodent animals.And also OB neuronal activity shows the circadian oscillation,which is independent of the circadain rhythms of suprachiasmatic nucleus.Base on the role of OB in both pathogenesis of depression and regulation of circadian rhythm,we speculate that OB may play an important regulatory role in the change of circadian rhythms in depressed rats.Thus,we will discuss the changes of OB circadian genes and the role of OB circadian genes in the pathogenesis of depression.We firstly establish the depression rat model by clomipramine(CLI)treatment.Then we observed the changes of circadian genes and the neurotransmitters in the depression model rats.We then change OB circadian gene expression in depression model rats and observe the depressed behaviors after the circadian genes changing.The experiment results showed that the expression of Per2 gene in the OB was significantly increased at ZT14,indicating that there was a rhythm disorder in OB within the depression.Knocking down Per2 significantly reversed the depressive behavior in depression model rats,such as alleviating the anhedonia behavior,olfactory dysfunction and social dysfunction of depressed rats.This result indicating that the Per2 gene in OB is important in the pathogenesis of depression.The Per2 gene of OB in rats plays an important role in the pathogenesis of depression in rats.Knocking down the Per2 expression in OB can reverse the depressive symptoms by increasing dopamine receptor expression and decreasing dopamine metabolism.