GABA Neurotransmitters Regulate Anoxia Stress Of C. Elegans By Excitatory Receptor EXP-1

Stroke is a very common cerebrovascular disease,which is divided into ischemic and hemorrhagic.The vast majority of stroke patients are ischemic stroke,that is,cerebral ischemia.Many researches focus on this disease.In the early stage of the project,a feasible model of anoxia and starvation of C.elegans was established to simulate cerebral ischemia,and some reverse genetic screening was carried out.After screening all neurotransmitter mutants,we found that GABA neurotransmitter had a protective effect on the anoxia of C.elegans.In addition to the phenotype of hypoxic survival,it was also confirmed by changes in ATP levels that C.elegans had more severe hypoxia injury after loss GABA.This project aim to explore the protective mechanism of GABA neurotransmitter in anoxia.Through neuron specific rescue and exogenous GABA addition experiments,we find that this protective effect is exercised by 7 GABAergic neurons in the head and tail,and independ on 19 D type motor neurons,so our project focus on 7 GABAergic neurons in head and tail.We will continue to identify the special neurons that work in the anoxia of C.elegans according to some results.In order to determine which GABA receptor is activated to alleviates the anoxia injury,four GABA receptors were screened.Then found the EXP-1 loss function mutant showed the same hypoxia sensitive phenotype with the GABA loss mutant unc-25(e156).It is verified by experiments that the hypoxia sensitive phenotype of exp-1(sa6)is caused by GABA's inability to perform its excitatory function.GABA usually performs its inhibitory function,while in our project,the hypoxia protection of GABA was completed by excitatory receptors.In order to find the related signaling of GBAB in anoxia,we analyzed the transcriptome sequencing data.It was found that the expression of fatty acid metabolism related genes in unc-25(e156)after hypoxia was significantly different from that the wild type after anoxia,indicating the hypoxia protection effect of GABA in C.elegans was related to the fatty acid metabolism.