TY  - JOUR
AU  - Ware, Kierra
AU  - Peter, Joshua
AU  - Yazell, Jake
AU  - Thapa, Christina
AU  - Taranov, Aleksandr
AU  - Bedolla, Alicia
AU  - Distel, Claire
AU  - Lammich, Sven
AU  - Feederle, Regina
AU  - Sülzen, Alice
AU  - Liddelow, Shane
AU  - Roskin, Krishna
AU  - Luo, Yu
TI  - Inhibition of TGF-β signaling in microglia stimulates hippocampal adult neurogenesis and reduces anxiety-like behavior in adult mice.
JO  - Nature Communications
VL  - 17
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2026-00183
SP  - 1440
PY  - 2026
AB  - 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.
KW  - Animals
KW  - Microglia: metabolism
KW  - Microglia: drug effects
KW  - Neurogenesis: physiology
KW  - Neurogenesis: drug effects
KW  - Neurogenesis: genetics
KW  - Anxiety: metabolism
KW  - Anxiety: genetics
KW  - PTEN Phosphohydrolase: metabolism
KW  - Hippocampus: metabolism
KW  - Hippocampus: cytology
KW  - Signal Transduction: drug effects
KW  - Mice, Knockout
KW  - TOR Serine-Threonine Kinases: metabolism
KW  - Mice
KW  - Doublecortin Protein
KW  - Receptor, Transforming Growth Factor-beta Type II: genetics
KW  - Receptor, Transforming Growth Factor-beta Type II: metabolism
KW  - Receptor, Transforming Growth Factor-beta Type I: genetics
KW  - Receptor, Transforming Growth Factor-beta Type I: metabolism
KW  - Male
KW  - Transforming Growth Factor beta: metabolism
KW  - Behavior, Animal
KW  - Mice, Inbred C57BL
KW  - Sirolimus: pharmacology
KW  - Transforming Growth Factor beta1: metabolism
KW  - Transforming Growth Factor beta1: genetics
KW  - PTEN Phosphohydrolase (NLM Chemicals)
KW  - TOR Serine-Threonine Kinases (NLM Chemicals)
KW  - mTOR protein, mouse (NLM Chemicals)
KW  - Doublecortin Protein (NLM Chemicals)
KW  - Pten protein, mouse (NLM Chemicals)
KW  - Dcx protein, mouse (NLM Chemicals)
KW  - Receptor, Transforming Growth Factor-beta Type II (NLM Chemicals)
KW  - Receptor, Transforming Growth Factor-beta Type I (NLM Chemicals)
KW  - Tgfbr2 protein, mouse (NLM Chemicals)
KW  - Transforming Growth Factor beta (NLM Chemicals)
KW  - Sirolimus (NLM Chemicals)
KW  - Tgfbr1 protein, mouse (NLM Chemicals)
KW  - Transforming Growth Factor beta1 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41663429
C2  - pmc:PMC12886940
DO  - DOI:10.1038/s41467-026-68885-4
UR  - https://pub.dzne.de/record/285161
ER  -