The Study Of GABA Neurotransmitters In The Regulation Of Anoxia In Caenorhabditis Elegans

Cerebral stroke is the leading cause of disability and death among adulthood over 60 years of age in the world,while the mechanism underlying neuronal death and dysfunction remains poorly understood.There are several models of animals used to simulate stroke currently,one of them is Caenorhabditis elegans(C.elegans)that has respond mechanism upon environment of oxygen concentration fluctuation,and its regulatory genes may be homologous to humans.It has the advantages of easy cultivation and operation has become a good model for studying the response and regulation mechanism of stroke.There are many equipments that are utilized to treat C.elegans with different oxygen concentration.Some molecular pathways that are conserved in humans that involved in hypoxia and anoxia regulation have been discovered in C.elegans.The C.elegans nervous system plays an important role in its survival and development.It resopns and adapts the change of oxygen concentration through the action of a series of sensory neurons and neural circuits.It is indicated that the C.elegans 's nervous system participates in the regulation of behavior and physiological activities under fluctuations of oxygen concentration.Neurotransmitters in C.elegans are important chemicals in the transmission of information in the nervous system,and participate in the regulation of physiological activities such as behavior and lifespan of nematodes.The regulation of the C.elegans 's nervous system and neurotransmitters in their anoxia remains to be studied.In this paper,We constructed a anoxic device to study the regulation and molecular mechanism of nervous system and neurotransmitter on its anoxia survival in C.elegans.We found that the wild type entered the suspended state and caused tissue damage after anoxia treatment in a self-made anoxic device.And the survival decreased with the prolongation of anoxia time.Treated by 99.99% nitrogen,20? for 72 hours followed by recovery for 24 hours,the survival of wild-type animals was about 60%.We tested the survival of some mutants of which genes encoding different types of neurotransmitters,found that the gamma-aminobutyric acid(GABA)synthesis-related mutant unc-25(e156)was hypersensitive to anoxia.We found that GABA neurotransmitter are involved in the anoxia survival of C.elegans through endogenous rescue.And through the specific rescue,we found GABA neurotransmitter plays a role in regulating anoxia survival in RMEs,AVL,DVB,RIS neurons rather than D-type motor neurons.We sequenced the transcriptome and found that anoxia affects the level of gene expression in C.elegans,and the unc-25 mutate affects the expression of genes under anoxia in C.elegans.We also found that the C.elegans anoxia-sensitive signaling pathway caused by GABA mutate in unc-25 mutation may be related to hyl-2 signaling pathway.We established a C.elegans anoxia model and found that GABA neurotransmitter was involved in the anoxia regulation in C.elegans,and providing information for the study of neural damage and its regulatory mechanisms caused by stroke.