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A cytosine\u20105 RNA methyltransferase,\n                    <jats:italic>NSUN5<\/jats:italic>\n                    , is one of the deleted genes, which has been linked to cognitive deficits in WBS patients. However, the relation of NSUN5 to anxiety disorders and underlying mechanisms remain unknown. Here, we report that NSUN5 deficiency triggers anxiety\u2010like behaviors without hypersociality in both adult male and female mice. NSUN5 exhibits specific expression in oligodendrocyte precursor cells (OPCs) within the basolateral amygdala (BLA), which is one of the main brain regions linked to anxiety. In addition, NSUN5 deficiency in mice leads to reduced OPCs proliferation accompanied with microglial activation. Mechanistically, we revealed that the specific decline in secretion of OPCs\u2010derived fibroblast growth factor 2 (FGF2) resulted in microglial activation and exacerbated the levels of TNF\u03b1 and IL\u20101\u03b2 cytokines in NSUN5\u2010deficient mice. Field excitatory postsynaptic potentials (fEPSPs) slopes at external capsule BLA synapse were increased in NSUN5\u2010deficient mice. Moreover, an increase in paired\u2010pulse inhibition and an impairment of long\u2010term depression (LTD) induction were observed in NSUN5\u2010deficient mice, which could be rescued either by intra\u2010BLA injection of recombinant mouse FGF2 (rmFGF2) or by pharmacological suppression of microglial activation with minocycline. Furthermore, the anxiety\u2010like behaviors in NSUN5\u2010deficient mice were also relieved by rmFGF2 or minocycline treatments. Taken together, our study unveils a previously unknown effect of NSUN5 on anxiety disorders and a role of NSUN5 in regulating OPCs\u2010microglia interaction and synaptic plasticity of BLA.\n                  <\/jats:p>","DOI":"10.1096\/fj.202600754r","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:33:19Z","timestamp":1777447999000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>NSUN5<\/scp>\n                    Deficiency Drives Anxiety\u2010Like Behaviors in Mice via Increased Microglial Activation and Impaired\n                    <scp>LTD<\/scp>\n                    Induction in the Basolateral Amygdala"],"prefix":"10.1096","volume":"40","author":[{"given":"Kailing","family":"He","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences Nanjing Normal University  Nanjing 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