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Cell Rep. 2016 Oct 18;17(4):941-948. doi: 10.1016/j.celrep.2016.09.075.

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

Author information

1
German Centre for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association, Arnoldstrasse 18, 01307 Dresden, Germany; DFG-Center for Regenerative Therapies Dresden (CRTD), Cluster of Excellence, TU Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
2
B CUBE, Center for Molecular Bioengineering, TU Dresden, Arnoldstrasse 18, 01307, Dresden, Germany.
3
Neuroscience Paris-Saclay Institute, AMATrace Platform, UMR 9197, CNRS, Avenue de la Terrasse, 91190 Gif-sur-Yvette, France.
4
DFG-Center for Regenerative Therapies Dresden (CRTD), Cluster of Excellence, TU Dresden, Fetscherstrasse 105, 01307 Dresden, Germany; Biotechnology Center (BIOTEC), TU Dresden, Tatzberg 47, 01307 Dresden, Germany.
5
German Centre for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association, Arnoldstrasse 18, 01307 Dresden, Germany; DFG-Center for Regenerative Therapies Dresden (CRTD), Cluster of Excellence, TU Dresden, Fetscherstrasse 105, 01307 Dresden, Germany. Electronic address: caghan.kizil@dzne.de.

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.

KEYWORDS:

Alzheimer’s disease; Amyloid-β42; STAT6; inflammation; interlukin-4; neural stem cell; neuro-immune crosstalk; neurodegeneration; regeneration; zebrafish

PMID:
27760324
DOI:
10.1016/j.celrep.2016.09.075
[Indexed for MEDLINE]
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