A Research On PrP-like Shadoo Regulate Depression Mechanism

Depressive disorder is a commonly occurring, debilitating, and life threateningpsychiatric disorder, always characterized by a pervasive low mood, loss of interest orpleasure in daily activities and suicidal tendencies.As the World Health Organization (WHO) statisticsed, depression is the world’smost common mental disorder and a leading cause of disability. Approximately350million people worldwide suffer from depression, resulting in decreased quality of lifeand major economic loss. Depression is serious public health problem with a life timeprevalent of about15%-20%，and it’s become more and more. In China, about55million people is suffering in depression, which is about8%of the totalpopulation.According to the World Health Organization (WHO), by the year2030,depression will result in more years of life lost to disability than other illness.Shadoo protein screened by Genomics approach is similar to prion protein（PrP）.Its encoding gene is Sprn. We has found that mice has typical symptoms of depressionwhen Sprn gene is knocked out. Shadoo protein has the nerve protective effect similarto prion protein. It can take part in regulating a variety of neural physiological andbiochemical process, and it plays an important part in regulating the nervous systemfunction. This paper takes Sprn gene knockout mice as models comparing withwild-type to study the regulation effect of Shadoo protein.This experiment mainly includes four parts:1）Build Sprn knockout mice strain,and screen Sprn knockout double chromosome homozygous mice;2)Useneurobehavioral to test the depression and despair of Sprn knockout micet;3）Observe and count the density of the CA1area neurons and the cerebral cortexneurons of Sprn knockout mice by using Golgi staining method to ensure the effect ofShadoo protein on neuron damage and the regenerative capacity;4）Examine thechanges of protein expression in brain by using2-DE method. Ensure the changes ofprotein and detect the neurotransmitter related to depression, the gene of neurotransmitter receptor and protein expression by using RT-PCR and Western blot.Conclusion:1) Successful build Sprn knockout mice stain, and screen out Sprnknockout double-chromosome homozygotes mice for research use.2) We have verified the deficiency of Shadoo protein lead mice to significantdepressive and desperation behavior with neuroethology test.3）The neuron density in hippocampus CA1and cerebral cortex of Sprn knockoutmic shows clear reducing compared with Wild-type mice, the deletion of Shadooresults in neuron damage and regeneration capacity declined.4) And we have detected multiple mRNA expression with RT-PCR whose gene isrelated to depression research, the mRNA expression of5-HT、DA、NE、BDNF、IL-6、5-HT-receptor-1A and DA-receptor-1decreases, but other5-HT-receptor subtype andother DA-receptor subtype didn’t show exchange in RT-PCR. The5-HT-receptor-1Aexpression reduced compared to Wild-type mice in Western blot, but DA-transporterexpression didn’t show obvious change.