IL4/STAT6 Signaling Activates Neural Stem Cell Proliferation and Neurogenesis upon Amyloid-β42 Aggregation in Adult Zebrafish Brain

Research output: Contribution to journalResearch articleContributedpeer-review



Human brains are prone to neurodegeneration, given that endogenous neural stem/progenitor cells (NSPCs) fail to support neurogenesis. To investigate the molecular programs potentially mediating neurodegeneration-induced NSPC plasticity in regenerating organisms, we generated an Amyloid-β42 (Aβ42)-dependent neurotoxic model in adult zebrafish brain through cerebroventricular microinjection of cell-penetrating Aβ42 derivatives. Aβ42 deposits in neurons and causes phenotypes reminiscent of amyloid pathophysiology: apoptosis, microglial activation, synaptic degeneration, and learning deficits. Aβ42 also induces NSPC proliferation and enhanced neurogenesis. Interleukin-4 (IL4) is activated primarily in neurons and microglia/macrophages in response to Aβ42 and is sufficient to increase NSPC proliferation and neurogenesis via STAT6 phosphorylation through the IL4 receptor in NSPCs. Our results reveal a crosstalk between neurons and immune cells mediated by IL4/STAT6 signaling, which induces NSPC plasticity in zebrafish brains.


Original languageEnglish
Pages (from-to)941-948
Number of pages8
JournalCell Reports
Issue number4
Publication statusPublished - 18 Oct 2016

External IDs

Scopus 84994807615
PubMed 27760324
ORCID /0000-0001-5624-1717/work/142238994
ORCID /0000-0002-6669-4995/work/142251821



  • Aging/pathology, Amyloid beta-Peptides/metabolism, Animals, Brain/metabolism, Cell Plasticity, Cell Proliferation, Interleukin-4/metabolism, Microglia, Nerve Degeneration/pathology, Neural Stem Cells/cytology, Neurogenesis, Neurons, Peptide Fragments/metabolism, Phenotype, Protein Aggregates, STAT6 Transcription Factor/metabolism, Signal Transduction, Zebrafish/metabolism