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

Prabesh Bhattarai | Zendy; Alvin Kuriakose Thomas | Zendy; Mehmet İlyas Coşacak | Zendy; Christos Papadimitriou | Zendy; Violeta Mashkaryan | Zendy; Cynthia Froc | Zendy; Susanne Reinhardt | Zendy; Thomas Kurth | Zendy; Andreas Dahl | Zendy; Yixin Zhang | Zendy; Çağhan Kızıl | Zendy

Open Access

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

Author(s) -

Prabesh Bhattarai,

Alvin Kuriakose Thomas,

Mehmet İlyas Coşacak,

Christos Papadimitriou,

Violeta Mashkaryan,

Cynthia Froc,

Susanne Reinhardt,

Thomas Kurth,

Andreas Dahl,

Yixin Zhang,

Çağhan Kızıl

Publication year - 2016

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.09.075

Subject(s) - neurogenesis , zebrafish , neurodegeneration , neural stem cell , microbiology and biotechnology , biology , microglia , neuroscience , progenitor cell , stem cell , immunology , inflammation , medicine , biochemistry , disease , gene

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.

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