PUBLICATION

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

Authors
Bhattarai, P., Thomas, A.K., Cosacak, M.I., Papadimitriou, C., Mashkaryan, V., Froc, C., Reinhardt, S., Kurth, T., Dahl, A., Zhang, Y., Kizil, C.
ID
ZDB-PUB-161025-31
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
Datasets
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.
Abstract
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes