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

Jiqing Xu; Fred De Winter; Catherine Farrokhi; Edward Rockenstein; Michael Mante; Anthony Adame; Jonathan Cook; Xin Jin; Eliezer Masliah; Kuo Fen Lee

doi:10.1038/srep31692

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

Jiqing Xu, Fred De Winter, Catherine Farrokhi, Edward Rockenstein, Michael Mante, Anthony Adame, Jonathan Cook, Xin Jin, Eliezer Masliah, Kuo Fen Lee^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

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.

Original language	English
Article number	31692
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep31692
State	Published - 25 Aug 2016
Externally published	Yes

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title = "Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer's disease model",

abstract = "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.",

author = "Jiqing Xu and \{De Winter\}, Fred and Catherine Farrokhi and Edward Rockenstein and Michael Mante and Anthony Adame and Jonathan Cook and Xin Jin and Eliezer Masliah and Lee, \{Kuo Fen\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2016.",

year = "2016",

month = aug,

day = "25",

doi = "10.1038/srep31692",

language = "英语",

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T1 - Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer's disease model

AU - Xu, Jiqing

AU - De Winter, Fred

AU - Farrokhi, Catherine

AU - Rockenstein, Edward

AU - Mante, Michael

AU - Adame, Anthony

AU - Cook, Jonathan

AU - Jin, Xin

AU - Masliah, Eliezer

AU - Lee, Kuo Fen

PY - 2016/8/25

Y1 - 2016/8/25

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84983792828

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DO - 10.1038/srep31692

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AN - SCOPUS:84983792828

SN - 2045-2322

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 31692

ER -

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

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