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Stress-induced neuroepigenetic programming gains growing more and more interest in the studies of the etiology of posttraumatic stress disorder (PTSD). However, seldom attention is focused on DNA demethylation in fear memory generalization, which is the core characteristic of PTSD. Here, we show that ten-eleven translocation protein 3 (TET3), the most abundant DNA demethylation enzyme of the TET family in neurons, senses environmental stress and bridges neuroplasticity with behavioral adaptation during fear generalization. Foot shock strength dependently induces fear generalization and TET3 expression in nucleus accumbens (NAc) in mice. Inhibition of DNA demethylation by infusing demethyltransferase inhibitors or AAV-Tet3-shRNA virus in NAc enhances the fear generalization and anxiety-like behavior. Furthermore, TET3 knockdown impairs the dendritic spine density, PSD length, and thickness of neurons, decreases DNA hydroxymethylation (5hmC), reduces the expression of synaptic plasticity-related genes including Homer1, Cdkn1a, Cdh8, Vamp8, Reln, Bdnf, while surprisingly increases immune-related genes Stat1, B2m, H2-Q7, H2-M2, C3, Cd68 shown by RNA-seq. Notably, knockdown of TET3 in NAc activates microglia and CD39-P2Y12R signaling pathway, and inhibition of CD39 reverses the effects of TET3 knockdown on the fear memory generalization and anxiety. Overexpression of TET3 by Crispr-dSaCas9 virus delivery to activate endogenous Tet3 in NAc increases dendritic spine density of neurons in NAc and reverses fear memory generalization and anxiety-like behavior in mice. These results suggest that TET3 modulates fear generalization and anxiety via regulating synaptic plasticity and CD39 signaling pathway.

Irritable Bowel Syndrome (IBS) is a physiological intestinal illness that is commonly accompanied with abdominal pain and changes in stool shape. Fecal Microbiota Transplantation (FMT) is a novel cure in intestinal diseases and an effective way to repopulate the gut flora. Paper will provide a comprehensive introduction to FMT and IBS, as well as a review of several studies on the value of FMT for IBS. It can be found in the studies that after short-term FMT treatment, patients' IBS-related symptoms were significantly improved, and only a few patients had minor intestinal problems such as diarrhea and constipation, and no serious intestinal disease. However, the effect of long-term treatment has not been further demonstrated, the IBS-related symptoms may recur in some patients, and the safety of long-term treatment has not been confirmed by experiments., this research examines the factors influencing FMT and the treatment's safety, as well as the potential clinical application of FMT for IBS. This will be an important topic for some time in the future, but it is certain that FMT will become one of the important treatment methods for IBS.