Study On The Mechanism Of Tet1 Protein Regulating Astrocyte Function Affecting Learning And Memory In Mice

5-hydroxymethylcytosine(5hm C)modification is a stable epigenetic modification in brain tissue and plays a vital role in the development of brain tissue and the maintenance of the function of brain nerve cells,but there are few studies on the function of 5hm C in astrocytes.We have found that lacking Tet1(Tet methylcytosine dioxygenase 1)protein result in a significant decrease in the level of 5hm C in astrocytes,and the ability of learning and memorization was significantly impaired after Tet1 protein was knocked out in adult astrocytet.Golgi staining of mouse brain slices showed that the conditional knockout of Tet1 protein in adult mice astrocytes had a great influence on the morphology of astrocytes and neurons in the hippocampus CA1 region,and their complexity and dentrites length were significantly reduced.The same phenotype was found in co-culture experiments in vitro.High-throughput sequencing was added to Tet1 KO astrocytes,and the analysis results showed a large number of down-regulated genes enriched in the functions related to the response to external stimuli,and most of them had the Gria1 gene encoding Glu A1 protein.The h Me IP-seq results showed that most of the 5hm C modifications were lost in the Gria1 promoter region.Calcium fluctuation showed that Tet1 KO astrocytes had very weak response to ATP,which could be rescued by overexpressed Glu A1 protein.This result proved that Glu A1 deficiency is the main cause of Tet1 KO astrocyte calcium wave disorder,and will lead to astrocyte and neuron communication disorder,and affect the learning and memorization function of the mice.This study explored the mechanism of Tet1 protein regulating astrocyte function and affecting the learning and memorization ability in mice.