title: IL4/STAT6 Signaling Activates Neural Stem Cell Proliferation and Neurogenesis upon Amyloid-β42 Aggregation in Adult Zebrafish Brain.
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.
authors.affiliation: 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.
authors.forename: Prabesh
authors.initials: P
authors.lastname: Bhattarai
authors.affiliation: B CUBE, Center for Molecular Bioengineering, TU Dresden, Arnoldstrasse 18, 01307, Dresden, Germany.
authors.forename: Alvin Kuriakose
authors.initials: AK
authors.lastname: Thomas
authors.affiliation: 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.
authors.forename: Mehmet Ilyas
authors.initials: MI
authors.lastname: Cosacak
authors.affiliation: 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.
authors.forename: Christos
authors.initials: C
authors.lastname: Papadimitriou
authors.affiliation: 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.
authors.forename: Violeta
authors.initials: V
authors.lastname: Mashkaryan
authors.affiliation: Neuroscience Paris-Saclay Institute, AMATrace Platform, UMR 9197, CNRS, Avenue de la Terrasse, 91190 Gif-sur-Yvette, France.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Froc
authors.affiliation: 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.
authors.forename: Susanne
authors.initials: S
authors.lastname: Reinhardt
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kurth
authors.affiliation: 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.
authors.forename: Andreas
authors.initials: A
authors.lastname: Dahl
authors.affiliation: B CUBE, Center for Molecular Bioengineering, TU Dresden, Arnoldstrasse 18, 01307, Dresden, Germany.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Caghan
authors.initials: C
authors.lastname: Kizil
mesh_terms: D000375:Aging / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D000066670:Cell Plasticity; D049109:Cell Proliferation; D015847:Interleukin-4 / Q000378:metabolism*; D017628:Microglia; D009410:Nerve Degeneration / Q000473:pathology; D058953:Neural Stem Cells / Q000166:cytology; D055495:Neurogenesis; D009474:Neurons; D010446:Peptide Fragments / Q000378:metabolism*; D010641:Phenotype; D066329:Protein Aggregates; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D066329:Protein Aggregates; D050800:STAT6 Transcription Factor; C075222:amyloid beta-protein (1-42); D015847:Interleukin-4
keywords: Alzheimer’s disease; Amyloid-β42; STAT6; inflammation; interlukin-4; neural stem cell; neuro-immune crosstalk; neurodegeneration; regeneration; zebrafish