Mechanism Of Inositol Hexaphosphate Kinase 1 (IP6K1) In Neurodevelopment And Synaptic Conduction

Background/Aims: The morphology and development of neurons mainly involve the growth branches of neuronal dendrites and axons,as well as the formation and reorganization of synapses.The formation and reorganization of synapses require the interaction between presynaptic and postsynaptic neurons.Neuron maturation is a complex process that requires the interaction of multiple factors,including gene expression,neurotrophin,synaptic signaling pathway,etc.Neurons are susceptible to gene and environmental influences during development,and neural dysplasia may lead to nervous system disease,such as autism.The maturation of neurons is an important link in the development of the nervous system,and it is crucial for the normal functioning of the nervous system.Inositol hexakisphosphate kinase 1(IP6K1)is an intracellular signaling regulatory factor that participates in various physiological and pathological processes,including cell proliferation,apoptosis,and metabolic regulation.Recent studies have found that IP6K1 also plays an important role in neurons,including synaptic formation and plasticity regulation,neuronal development and protection,and participation in nervous system disease.Therefore,this study explores the role and possible mechanisms of IP6K1 in neuronal development.This research is of great significance for understanding the pathogenesis of nervous system disease and developing relevant treatment methods.Materials: Immunofluorescence detection of localization and expression of IP6K1 in neurons;Western blot detects the expression of IP6K1 in mouse brain and rat neurons during development;Immunofluorescence detection of neuronal dendritic number,dendritic length,and axon length using IP6K1 active inhibitor[N2-(m-(trifluoromethyl)benzyl)N6-(p-nitrobenzyl)purine][N2-(m-trifluorobenzyl),TNP];Immunofluorescence detects synaptic density in neurons.A primary neuronal model of lentiviral transfected rats was established,simulating in vitro knockdown IP6K1 expression,immunofluorescence and Western blot to detect the expression levels of IP6K1 downstream pathways GSK3β and AMPK.Results: The experimental results showed that the expression of IP6K1 in neurons increased with age(P<0.05 or P<0.01).Inhibition of IP6K1 activity,the number and length of dendrites increase during neuronal development(P<0.05 or P<0.01);Increased axon length during neuronal development(P<0.05 or P<0.01);Increased synaptic density in neurons(P<0.05 or P<0.01).By knocking down IP6K1,the number of dendrites of neurons increases(P<0.01);Neuronal axon length increases(P<0.01).While inhibiting the expression of IP6K1,the GSK3β signaling pathway was inhibited(P<0.05)and the AMPK pathway was activated(P<0.05).Conclusion: IP6K1 is expressed in neurons,its expression increases with age,after inhibiting IP6K1,neuronal axondrite synapses will overgrow leading to autism,IP6K1 knockdown prevents dendritic axon overgrowth by inhibiting GSK3β signaling pathway and activating AMPK signaling pathway,IP6K1 physiologically inhibits synaptic axon dendritic overgrowth for normal neuronal development and is very important.