title: Brain intraventricular injection of amyloid-β in zebrafish embryo impairs cognition and increases tau phosphorylation, effects reversed by lithium.
abstract: Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no effective treatment and commonly diagnosed only on late stages. Amyloid-β (Aβ) accumulation and exacerbated tau phosphorylation are molecular hallmarks of AD implicated in cognitive deficits and synaptic and neuronal loss. The Aβ and tau connection is beginning to be elucidated and attributed to interaction with different components of common signaling pathways. Recent evidences suggest that non-fibrillary Aβ forms bind to membrane receptors and modulate GSK-3β activity, which in turn phosphorylates the microtubule-associated tau protein leading to axonal disruption and toxic accumulation. Available AD animal models, ranging from rodent to invertebrates, significantly contributed to our current knowledge, but complementary platforms for mechanistic and candidate drug screenings remain critical for the identification of early stage biomarkers and potential disease-modifying therapies. Here we show that Aβ1-42 injection in the hindbrain ventricle of 24 hpf zebrafish embryos results in specific cognitive deficits and increased tau phosphorylation in GSK-3β target residues at 5dpf larvae. These effects are reversed by lithium incubation and not accompanied by apoptotic markers. We believe this may represent a straightforward platform useful to identification of cellular and molecular mechanisms of early stage AD-like symptoms and the effects of neuroactive molecules in pharmacological screenings.
authors.affiliation: ZebLab & Laboratório de Biologia e Desenvolvimento do Sistema Nervoso, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Laura Roesler
authors.initials: LR
authors.lastname: Nery
authors.affiliation: ZebLab & Laboratório de Biologia e Desenvolvimento do Sistema Nervoso, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Natalia Silva
authors.initials: NS
authors.lastname: Eltz
authors.affiliation: ZebLab & Laboratório de Biologia e Desenvolvimento do Sistema Nervoso, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Hackman
authors.affiliation: ZebLab & Laboratório de Biologia e Desenvolvimento do Sistema Nervoso, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Raphaela
authors.initials: R
authors.lastname: Fonseca
authors.affiliation: ZebLab & Laboratório de Neuroquímica e Psicofarmacologia, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Stefani
authors.initials: S
authors.lastname: Altenhofen
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Heydi Noriega
authors.initials: HN
authors.lastname: Guerra
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Vanessa Morais
authors.initials: VM
authors.lastname: Freitas
authors.affiliation: ZebLab & Laboratório de Neuroquímica e Psicofarmacologia, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
authors.affiliation: ZebLab & Laboratório de Biologia e Desenvolvimento do Sistema Nervoso, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Monica Ryff Moreira Roca
authors.initials: MR
authors.lastname: Vianna
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007276:Injections, Intraventricular; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D029961:Zebrafish Proteins; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D008094:Lithium; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3