The Effects Of Sphingomyelin On Mouse Behavior,Metabolism And Neurotransmitter

ATP13A2 encoded by the gene of ATP13A2 is a lysosome transmembrane transporter which belongs to P5 B subfamily.ATP13A2 mutation often causes the early stage Parkinson's Disease(PD)and Kufor-Rakeb syndrome which will lead to motor disability,self-control disorder and dopaminergic neuronfunction loss.However,it's still unclear of the function and substrates of ATP13A2.Some evidences show that ATP13A2 may be involved in metal ion transportation,mitochondrion function and lysosome-autophage.In addition,the clinical studies show that the deficiency of ATP13A2 could enhance neuronal ceroid lipofuscinosis in brain,which indicate that ATP13A2 deficiency might entrain dyshomeostasis of trace metals and lipids moieties between the sides of lysosomal membrane.Depending on our former study,we found that the deficiency of ATP13A2 in mouse shows movement disorder,compulsive-control disorder and an increasement of sphingomyelin.We suppose that ATP13A2 might be a transporter of sphingomyelin and the deficiency of ATP13A2 may lead to the increasement of sphingomyelin.So it might have an influence on the level of neurotransmitter in brain,the abnormal behavior might be the consequence of those events.In this study,we will focus on the effects of sphingomyelin on neurotransmitter level in SH-SY5 Y cell as well as on mouse behavior,metabolism and the level of neurotransmitter after sphingomyelin brain injection.Our results indicate that sphingomyelin brain injection really have an influence on mouse behavior of grooming and drinking,as well as dopamine level in hypothalamus and striatum corpora.