Home > In process > Inhibition of TGF-β signaling in microglia stimulates hippocampal adult neurogenesis and reduces anxiety-like behavior in adult mice. > print

001     285161
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024 7 _ |a 10.1038/s41467-026-68885-4
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037 _ _ |a DZNE-2026-00183
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Ware, Kierra
|0 0000-0001-6947-2514
|b 0
245 _ _ |a Inhibition of TGF-β signaling in microglia stimulates hippocampal adult neurogenesis and reduces anxiety-like behavior in adult mice.
260 _ _ |a [London]
|c 2026
|b Springer Nature
336 7 _ |a article
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520 _ _ |a Adult 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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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a PTEN Phosphohydrolase
|0 EC 3.1.3.67
|2 NLM Chemicals
650 _ 7 |a TOR Serine-Threonine Kinases
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 7 |a mTOR protein, mouse
|0 EC 2.7.1.1
|2 NLM Chemicals
650 _ 7 |a Doublecortin Protein
|2 NLM Chemicals
650 _ 7 |a Pten protein, mouse
|0 EC 3.1.3.67
|2 NLM Chemicals
650 _ 7 |a Dcx protein, mouse
|2 NLM Chemicals
650 _ 7 |a Receptor, Transforming Growth Factor-beta Type II
|0 EC 2.7.11.30
|2 NLM Chemicals
650 _ 7 |a Receptor, Transforming Growth Factor-beta Type I
|0 EC 2.7.11.30
|2 NLM Chemicals
650 _ 7 |a Tgfbr2 protein, mouse
|0 EC 2.7.11.30
|2 NLM Chemicals
650 _ 7 |a Transforming Growth Factor beta
|2 NLM Chemicals
650 _ 7 |a Sirolimus
|0 W36ZG6FT64
|2 NLM Chemicals
650 _ 7 |a Tgfbr1 protein, mouse
|0 EC 2.7.11.30
|2 NLM Chemicals
650 _ 7 |a Transforming Growth Factor beta1
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Microglia: drug effects
|2 MeSH
650 _ 2 |a Neurogenesis: physiology
|2 MeSH
650 _ 2 |a Neurogenesis: drug effects
|2 MeSH
650 _ 2 |a Neurogenesis: genetics
|2 MeSH
650 _ 2 |a Anxiety: metabolism
|2 MeSH
650 _ 2 |a Anxiety: genetics
|2 MeSH
650 _ 2 |a PTEN Phosphohydrolase: metabolism
|2 MeSH
650 _ 2 |a Hippocampus: metabolism
|2 MeSH
650 _ 2 |a Hippocampus: cytology
|2 MeSH
650 _ 2 |a Signal Transduction: drug effects
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a TOR Serine-Threonine Kinases: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Doublecortin Protein
|2 MeSH
650 _ 2 |a Receptor, Transforming Growth Factor-beta Type II: genetics
|2 MeSH
650 _ 2 |a Receptor, Transforming Growth Factor-beta Type II: metabolism
|2 MeSH
650 _ 2 |a Receptor, Transforming Growth Factor-beta Type I: genetics
|2 MeSH
650 _ 2 |a Receptor, Transforming Growth Factor-beta Type I: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Transforming Growth Factor beta: metabolism
|2 MeSH
650 _ 2 |a Behavior, Animal
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Sirolimus: pharmacology
|2 MeSH
650 _ 2 |a Transforming Growth Factor beta1: metabolism
|2 MeSH
650 _ 2 |a Transforming Growth Factor beta1: genetics
|2 MeSH
700 1 _ |a Peter, Joshua
|0 0000-0002-0943-9955
|b 1
700 1 _ |a Yazell, Jake
|b 2
700 1 _ |a Thapa, Christina
|0 0000-0003-0822-2911
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700 1 _ |a Taranov, Aleksandr
|0 0000-0001-5508-6671
|b 4
700 1 _ |a Bedolla, Alicia
|b 5
700 1 _ |a Distel, Claire
|b 6
700 1 _ |a Lammich, Sven
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700 1 _ |a Feederle, Regina
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700 1 _ |a Sülzen, Alice
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700 1 _ |a Liddelow, Shane
|0 0000-0002-0840-1437
|b 10
700 1 _ |a Roskin, Krishna
|0 0000-0002-5864-5093
|b 11
700 1 _ |a Luo, Yu
|0 0000-0002-7939-5505
|b 12
773 _ _ |a 10.1038/s41467-026-68885-4
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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