Journal Article

DZNE-2026-00183

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Inhibition of TGF-β signaling in microglia stimulates hippocampal adult neurogenesis and reduces anxiety-like behavior in adult mice.

Ware, K. ; Peter, J. ; Yazell, J. ; Thapa, C. ; Taranov, A. ; Bedolla, A. ; Distel, C. ; Lammich, S. ; Feederle, R.DZNE* ; Sülzen, A.DZNE* ; Liddelow, S. ; Roskin, K. ; Luo, Y.

2026
Springer Nature [London]

This record in other databases:    

Please use a persistent id in citations: doi:10.1038/s41467-026-68885-4

Abstract: 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.

Keyword(s): Animals (MeSH) ; Microglia: metabolism (MeSH) ; Microglia: drug effects (MeSH) ; Neurogenesis: physiology (MeSH) ; Neurogenesis: drug effects (MeSH) ; Neurogenesis: genetics (MeSH) ; Anxiety: metabolism (MeSH) ; Anxiety: genetics (MeSH) ; PTEN Phosphohydrolase: metabolism (MeSH) ; Hippocampus: metabolism (MeSH) ; Hippocampus: cytology (MeSH) ; Signal Transduction: drug effects (MeSH) ; Mice, Knockout (MeSH) ; TOR Serine-Threonine Kinases: metabolism (MeSH) ; Mice (MeSH) ; Doublecortin Protein (MeSH) ; Receptor, Transforming Growth Factor-beta Type II: genetics (MeSH) ; Receptor, Transforming Growth Factor-beta Type II: metabolism (MeSH) ; Receptor, Transforming Growth Factor-beta Type I: genetics (MeSH) ; Receptor, Transforming Growth Factor-beta Type I: metabolism (MeSH) ; Male (MeSH) ; Transforming Growth Factor beta: metabolism (MeSH) ; Behavior, Animal (MeSH) ; Mice, Inbred C57BL (MeSH) ; Sirolimus: pharmacology (MeSH) ; Transforming Growth Factor beta1: metabolism (MeSH) ; Transforming Growth Factor beta1: genetics (MeSH) ; PTEN Phosphohydrolase ; TOR Serine-Threonine Kinases ; mTOR protein, mouse ; Doublecortin Protein ; Pten protein, mouse ; Dcx protein, mouse ; Receptor, Transforming Growth Factor-beta Type II ; Receptor, Transforming Growth Factor-beta Type I ; Tgfbr2 protein, mouse ; Transforming Growth Factor beta ; Sirolimus ; Tgfbr1 protein, mouse ; Transforming Growth Factor beta1

---

Contributing Institute(s):

1. Antibody Production (AG Feederle)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

---

Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---