The Study On GABAergic Synapse Transmission Regulating The Innate Immunity Mechanism In Caenorhabditis Elegans

There is a close relationship between the nervous system and immune system,and the communication between them is important for maintaining normal life.The exchange between neuron and immunity can regulate the innate immune response by releasing neurotransmitters,neuropeptides and hormones.Both nerve cells and immune cells can synthesize and release neurotransmitters,hormones and cytokines,wich becomes the common biological language of the nervous system and the immune system.In recent years,more and more researchers have turned their attention to this topic,the interaction of the neuro-immune system.However,due to the complexity of mammalian brain and the limitation of clinical technology,the research on molecular mechanism at this area is still not deep enough.The Caenorhabditis elegans,as a model organism,has many biological advantages in studying innate immunity and has been accepted by more and more people.PA14 is a kind of conditional pathogens from clinic.We use it to replace the normal food E.coli in laboratory,which constitutes a C.elegans-PA14-host-pathogen model to research the interaction between pathogenic factors and innate immune response.Pathogen infection can activate the corresponding signal transduction pathway in the worm's innate immunity to fight pathogens,identifying and eliminating it.In this paper,a model of C.elegans-PA14-host-pathogen model is established to study the interaction of neuroimmunity.Previous studies have found that the mutant unc-49 has a longer life span than the wild type N2 during PA14 infection.Then,we do the rescue experiment about the expressing of GABAAR/ UNC-49 in body wall muscle and intestinal tissue.Other factors that may affect the longevity in the mutant of GABAAR/UNC-49 deletion are eliminated by PA14-GFP infection and CFU assay.We find that GABAAR/ UNC-49 expressed in muscle tissue could save the mutant unc-49 with an extended phenotype.Using fluorescence labeling technology,juIs1 and krSi2 is marked by GFP and RFP respectively.PA14 infection is able to increase the expression of presynaptic snb-1 and postsynaptic GABAAR.Further study shows that the expression of extracellular matrix protein MADD-4 is also increased after PA14 infection.We also find that the extension life span of the unc-49 mutant in PA14 is dependent on the regulation of DAF-2/DAF-16 pathway partly.The study on innate immunity of the C.elegans is indirectly linked to animals and plants,which can be good for us to understand the nerve complex function of human,animal and plant.It can also provide a new direction for the human nervous system related disease.