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000285161 037__ $$aDZNE-2026-00183
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000285161 1001_ $$00000-0001-6947-2514$$aWare, Kierra$$b0
000285161 245__ $$aInhibition of TGF-β signaling in microglia stimulates hippocampal adult neurogenesis and reduces anxiety-like behavior in adult mice.
000285161 260__ $$a[London]$$bSpringer Nature$$c2026
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000285161 520__ $$aAdult neurogenesis in the subgranular zone (SGZ) has been implicated in cognitive and affective functions. The role of neuroinflammation and reactive microglia in SGZ neurogenesis is not well understood. TGF-β signaling is critical to maintaining microglia homeostasis in the adult brain. To investigate the role of microglia in SGZ neurogenesis, using microglia-specific inducible knockout (iKO) mice for TGF-β1 ligand or receptor (Alk5 or Tgfbr2), here we show that TGF-β-deficient microglia increase adult neurogenesis in the SGZ, accompanied by altered anxiety-like behavior in KO mice. Single-cell RNAseq (ScRNAseq) analysis shows decreased PTEN signaling, and immunohistochemistry shows increased mTOR activity in DCX+ newly born neuroblasts at the SGZ in iKO mice. Inhibition of mTOR signaling by rapamycin reverses the heightened SGZ neurogenesis in iKO mice. This study reveals the role of microglia in regulating hippocampal adult neurogenesis via the PTEN-mTOR pathway and its potential implications for behavioral and affective functions.
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000285161 650_7 $$0EC 3.1.3.67$$2NLM Chemicals$$aPTEN Phosphohydrolase
000285161 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aTOR Serine-Threonine Kinases
000285161 650_7 $$0EC 2.7.1.1$$2NLM Chemicals$$amTOR protein, mouse
000285161 650_7 $$2NLM Chemicals$$aDoublecortin Protein
000285161 650_7 $$0EC 3.1.3.67$$2NLM Chemicals$$aPten protein, mouse
000285161 650_7 $$2NLM Chemicals$$aDcx protein, mouse
000285161 650_7 $$0EC 2.7.11.30$$2NLM Chemicals$$aReceptor, Transforming Growth Factor-beta Type II
000285161 650_7 $$0EC 2.7.11.30$$2NLM Chemicals$$aReceptor, Transforming Growth Factor-beta Type I
000285161 650_7 $$0EC 2.7.11.30$$2NLM Chemicals$$aTgfbr2 protein, mouse
000285161 650_7 $$2NLM Chemicals$$aTransforming Growth Factor beta
000285161 650_7 $$0W36ZG6FT64$$2NLM Chemicals$$aSirolimus
000285161 650_7 $$0EC 2.7.11.30$$2NLM Chemicals$$aTgfbr1 protein, mouse
000285161 650_7 $$2NLM Chemicals$$aTransforming Growth Factor beta1
000285161 650_2 $$2MeSH$$aAnimals
000285161 650_2 $$2MeSH$$aMicroglia: metabolism
000285161 650_2 $$2MeSH$$aMicroglia: drug effects
000285161 650_2 $$2MeSH$$aNeurogenesis: physiology
000285161 650_2 $$2MeSH$$aNeurogenesis: drug effects
000285161 650_2 $$2MeSH$$aNeurogenesis: genetics
000285161 650_2 $$2MeSH$$aAnxiety: metabolism
000285161 650_2 $$2MeSH$$aAnxiety: genetics
000285161 650_2 $$2MeSH$$aPTEN Phosphohydrolase: metabolism
000285161 650_2 $$2MeSH$$aHippocampus: metabolism
000285161 650_2 $$2MeSH$$aHippocampus: cytology
000285161 650_2 $$2MeSH$$aSignal Transduction: drug effects
000285161 650_2 $$2MeSH$$aMice, Knockout
000285161 650_2 $$2MeSH$$aTOR Serine-Threonine Kinases: metabolism
000285161 650_2 $$2MeSH$$aMice
000285161 650_2 $$2MeSH$$aDoublecortin Protein
000285161 650_2 $$2MeSH$$aReceptor, Transforming Growth Factor-beta Type II: genetics
000285161 650_2 $$2MeSH$$aReceptor, Transforming Growth Factor-beta Type II: metabolism
000285161 650_2 $$2MeSH$$aReceptor, Transforming Growth Factor-beta Type I: genetics
000285161 650_2 $$2MeSH$$aReceptor, Transforming Growth Factor-beta Type I: metabolism
000285161 650_2 $$2MeSH$$aMale
000285161 650_2 $$2MeSH$$aTransforming Growth Factor beta: metabolism
000285161 650_2 $$2MeSH$$aBehavior, Animal
000285161 650_2 $$2MeSH$$aMice, Inbred C57BL
000285161 650_2 $$2MeSH$$aSirolimus: pharmacology
000285161 650_2 $$2MeSH$$aTransforming Growth Factor beta1: metabolism
000285161 650_2 $$2MeSH$$aTransforming Growth Factor beta1: genetics
000285161 7001_ $$00000-0002-0943-9955$$aPeter, Joshua$$b1
000285161 7001_ $$aYazell, Jake$$b2
000285161 7001_ $$00000-0003-0822-2911$$aThapa, Christina$$b3
000285161 7001_ $$00000-0001-5508-6671$$aTaranov, Aleksandr$$b4
000285161 7001_ $$aBedolla, Alicia$$b5
000285161 7001_ $$aDistel, Claire$$b6
000285161 7001_ $$aLammich, Sven$$b7
000285161 7001_ $$0P:(DE-2719)2812867$$aFeederle, Regina$$b8
000285161 7001_ $$0P:(DE-2719)2810605$$aSülzen, Alice$$b9
000285161 7001_ $$00000-0002-0840-1437$$aLiddelow, Shane$$b10
000285161 7001_ $$00000-0002-5864-5093$$aRoskin, Krishna$$b11
000285161 7001_ $$00000-0002-7939-5505$$aLuo, Yu$$b12
000285161 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-026-68885-4$$gVol. 17, no. 1, p. 1440$$n1$$p1440$$tNature Communications$$v17$$x2041-1723$$y2026
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