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The Heterogeneity Of Astrocytes NDRG2 In Mouse Disease Models

Posted on:2020-11-01Degree:MasterType:Thesis
Country:ChinaCandidate:C Y BiFull Text:PDF
GTID:2404330578456892Subject:Zoology
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N-myc downstream-regulated gene 2(NDRG2)is a downstream regulatory gene of N-myc,which belongs to the alpha/beta hydrolase superfamily.NDRG2 belongs to the NDRG gene family together with NDRG1,NDRG3,and NDRG4.Studies have shown that NDRG2 is significantly reduced in many human tumor diseases such as colorectal cancer,breast cancer,malignant glioma and liver cancer,suggesting that one of the functions of NDRG2 is to inhibit the occurrence of human tumors.However,studies have now found that NDRG2 plays an important role in the nervous system in addition to inhibiting tumors,especially in certain neurological diseases.For example,NDRG2 promotes the axon and synaptic elongation and formation of neurons in the brain;in addition,NDRG2 is involved in the anti-apoptotic mechanism in the nervous system and neurological diseases such as depression and epilepsy in the rat model of cerebral ischemia.As a new treatment route.Recent studies NDRG2 in mice have shown that NDRG2 is abundantly mainly expressed in the neurogenesis sites of fetal and neonatal mouse brain regions.Furthermore,NDRG2 is expressed in astrocytes together with the astrocyte marker protein GFAP(Glial Fibrillary Acidic Protein),suggesting that it may be involved in the neurogenesis of the central nervous system.But so far,the expression pattern and mechanism of action of NDRG2 in brain disease models are still unclear.In this study,we selected three brain disease models,Huntington's Disease(HD),Traumatic brain injury(TBI),and Lipopolysaccharide(LPS).After the establishment of the three models,1w/2w/3w/4w,real-time PCR was used to detect the m RNA expression level of NDRG2 in hippocampus,cortex and striatum.The results showed that the m RNA level of NDRG2 increased at 1w/2w after HD and TBI modeling,while there was no significant change in the level of1w--4w NDRG2 after LPS modeling.At the same time,we also used NDRG2 and GFAP for immunofluorescence staining.Compared with the control group,the double staining results in the brain disease model showed that the proportion of NDRG2 and GFAP-positive cells in the brain tissue of the mice was significantly increased,and NDRG2 was mainly after brain injury.Expressed in astrocytes,suggesting that it is a stress response gene.Moreover,the average area of NDRG2+/GFAP+ astrocytes on the injured side was significantly larger than the average area of the opposite side of the lesion,indicating that astrocytes were activated in the brain after injury;and the number of NDRG2+/GFAP+ double positive cells in the injured side was significantly higher,this demonstrates that NDRG2 may have an effect on the state of astrocytes in a mouse model of brain injury disease,suggesting that NDRG2 expression may have potential therapeutic effects on certain brain injury diseases.This study initially explored the spatial and temporal expression of NDRG2 in normal and diseased brain tissues,and obtained the general trend of regional and temporal differences in NDRG2 expression in mouse brain disease models,in order to explore NDRG2 in brain disease models in the future.The specific role in the middle provides a good research basis.
Keywords/Search Tags:NDRG2, Huntington's disease, Traumatic brain injury, Lipopolysaccharide, Astrocytes, Central Nervous System, Heterogeneity
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