Brain intraventricular injection of amyloid-β in zebrafish embryo impairs cognition and increases tau phosphorylation, effects reversed by lithium.

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 l...

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Autores principales: Laura Roesler Nery, Natalia Silva Eltz, Cristiana Hackman, Raphaela Fonseca, Stefani Altenhofen, Heydi Noriega Guerra, Vanessa Morais Freitas, Carla Denise Bonan, Monica Ryff Moreira Roca Vianna
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Publicado: Public Library of Science (PLoS) 2014
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spelling oai:doaj.org-article:2937cbe091024d56a6e05c6625d6754b2021-11-25T06:01:56ZBrain intraventricular injection of amyloid-β in zebrafish embryo impairs cognition and increases tau phosphorylation, effects reversed by lithium.1932-620310.1371/journal.pone.0105862https://doaj.org/article/2937cbe091024d56a6e05c6625d6754b2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25187954/?tool=EBIhttps://doaj.org/toc/1932-6203Alzheimer'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.Laura Roesler NeryNatalia Silva EltzCristiana HackmanRaphaela FonsecaStefani AltenhofenHeydi Noriega GuerraVanessa Morais FreitasCarla Denise BonanMonica Ryff Moreira Roca ViannaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e105862 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Laura Roesler Nery
Natalia Silva Eltz
Cristiana Hackman
Raphaela Fonseca
Stefani Altenhofen
Heydi Noriega Guerra
Vanessa Morais Freitas
Carla Denise Bonan
Monica Ryff Moreira Roca Vianna
Brain intraventricular injection of amyloid-β in zebrafish embryo impairs cognition and increases tau phosphorylation, effects reversed by lithium.
description 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.
format article
author Laura Roesler Nery
Natalia Silva Eltz
Cristiana Hackman
Raphaela Fonseca
Stefani Altenhofen
Heydi Noriega Guerra
Vanessa Morais Freitas
Carla Denise Bonan
Monica Ryff Moreira Roca Vianna
author_facet Laura Roesler Nery
Natalia Silva Eltz
Cristiana Hackman
Raphaela Fonseca
Stefani Altenhofen
Heydi Noriega Guerra
Vanessa Morais Freitas
Carla Denise Bonan
Monica Ryff Moreira Roca Vianna
author_sort Laura Roesler Nery
title Brain intraventricular injection of amyloid-β in zebrafish embryo impairs cognition and increases tau phosphorylation, effects reversed by lithium.
title_short Brain intraventricular injection of amyloid-β in zebrafish embryo impairs cognition and increases tau phosphorylation, effects reversed by lithium.
title_full Brain intraventricular injection of amyloid-β in zebrafish embryo impairs cognition and increases tau phosphorylation, effects reversed by lithium.
title_fullStr Brain intraventricular injection of amyloid-β in zebrafish embryo impairs cognition and increases tau phosphorylation, effects reversed by lithium.
title_full_unstemmed Brain intraventricular injection of amyloid-β in zebrafish embryo impairs cognition and increases tau phosphorylation, effects reversed by lithium.
title_sort brain intraventricular injection of amyloid-β in zebrafish embryo impairs cognition and increases tau phosphorylation, effects reversed by lithium.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/2937cbe091024d56a6e05c6625d6754b
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