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Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model

Several lines of evidence suggest that neuregulin 1 (NRG1) signaling may influence cognitive function and neuropathology in Alzheimer’s disease (AD). To test this possibility, full-length type I or type III NRG1 was overexpressed via lentiviral vectors in the hippocampus of line 41 AD mouse. Both ty...

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Autores principales: Xu, Jiqing, de Winter, Fred, Farrokhi, Catherine, Rockenstein, Edward, Mante, Michael, Adame, Anthony, Cook, Jonathan, Jin, Xin, Masliah, Eliezer, Lee, Kuo-Fen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997345/
https://www.ncbi.nlm.nih.gov/pubmed/27558862
http://dx.doi.org/10.1038/srep31692
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author Xu, Jiqing
de Winter, Fred
Farrokhi, Catherine
Rockenstein, Edward
Mante, Michael
Adame, Anthony
Cook, Jonathan
Jin, Xin
Masliah, Eliezer
Lee, Kuo-Fen
author_facet Xu, Jiqing
de Winter, Fred
Farrokhi, Catherine
Rockenstein, Edward
Mante, Michael
Adame, Anthony
Cook, Jonathan
Jin, Xin
Masliah, Eliezer
Lee, Kuo-Fen
author_sort Xu, Jiqing
collection PubMed
description Several lines of evidence suggest that neuregulin 1 (NRG1) signaling may influence cognitive function and neuropathology in Alzheimer’s disease (AD). To test this possibility, full-length type I or type III NRG1 was overexpressed via lentiviral vectors in the hippocampus of line 41 AD mouse. Both type I and type III NRG1 improves deficits in the Morris water-maze behavioral task. Neuropathology was also significantly ameliorated. Decreased expression of the neuronal marker MAP2 and synaptic markers PSD95 and synaptophysin in AD mice was significantly reversed. Levels of Aβ peptides and plaques were markedly reduced. Furthermore, we showed that soluble ectodomains of both type I and type III NRG1 significantly increased expression of Aβ-degrading enzyme neprilysin (NEP) in primary neuronal cultures. Consistent with this finding, immunoreactivity of NEP was increased in the hippocampus of AD mice. These results suggest that NRG1 provides beneficial effects in candidate neuropathologic substrates of AD and, therefore, is a potential target for the treatment of AD.
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spelling pubmed-49973452016-09-01 Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model Xu, Jiqing de Winter, Fred Farrokhi, Catherine Rockenstein, Edward Mante, Michael Adame, Anthony Cook, Jonathan Jin, Xin Masliah, Eliezer Lee, Kuo-Fen Sci Rep Article Several lines of evidence suggest that neuregulin 1 (NRG1) signaling may influence cognitive function and neuropathology in Alzheimer’s disease (AD). To test this possibility, full-length type I or type III NRG1 was overexpressed via lentiviral vectors in the hippocampus of line 41 AD mouse. Both type I and type III NRG1 improves deficits in the Morris water-maze behavioral task. Neuropathology was also significantly ameliorated. Decreased expression of the neuronal marker MAP2 and synaptic markers PSD95 and synaptophysin in AD mice was significantly reversed. Levels of Aβ peptides and plaques were markedly reduced. Furthermore, we showed that soluble ectodomains of both type I and type III NRG1 significantly increased expression of Aβ-degrading enzyme neprilysin (NEP) in primary neuronal cultures. Consistent with this finding, immunoreactivity of NEP was increased in the hippocampus of AD mice. These results suggest that NRG1 provides beneficial effects in candidate neuropathologic substrates of AD and, therefore, is a potential target for the treatment of AD. Nature Publishing Group 2016-08-25 /pmc/articles/PMC4997345/ /pubmed/27558862 http://dx.doi.org/10.1038/srep31692 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Xu, Jiqing
de Winter, Fred
Farrokhi, Catherine
Rockenstein, Edward
Mante, Michael
Adame, Anthony
Cook, Jonathan
Jin, Xin
Masliah, Eliezer
Lee, Kuo-Fen
Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model
title Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model
title_full Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model
title_fullStr Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model
title_full_unstemmed Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model
title_short Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model
title_sort neuregulin 1 improves cognitive deficits and neuropathology in an alzheimer’s disease model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997345/
https://www.ncbi.nlm.nih.gov/pubmed/27558862
http://dx.doi.org/10.1038/srep31692
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