ZFIN ID: ZDB-PUB-161025-31
IL4/STAT6 Signaling Activates Neural Stem Cell Proliferation and Neurogenesis upon Amyloid-β42 Aggregation in Adult Zebrafish Brain
Bhattarai, P., Thomas, A.K., Cosacak, M.I., Papadimitriou, C., Mashkaryan, V., Froc, C., Reinhardt, S., Kurth, T., Dahl, A., Zhang, Y., Kizil, C.
Date: 2016
Source: Cell Reports   17: 941-948 (Journal)
Registered Authors: Bhattarai, Prabesh, Cosacak, Mehmet Ilyas, Froc, Cynthia, Kizil, Caghan, Papadimitriou, Christos
Keywords: Alzheimer’s disease, Amyloid-β42, STAT6, inflammation, interlukin-4, neural stem cell, neuro-immune crosstalk, neurodegeneration, regeneration, zebrafish
Microarrays: GEO:GSE74326
MeSH Terms:
  • Aging/pathology
  • Amyloid beta-Peptides/metabolism*
  • Animals
  • Brain/metabolism*
  • Brain/pathology
  • 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
PubMed: 27760324 Full text @ Cell Rep.
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.