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...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2016-08-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/srep31692 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585731303800832 |
|---|---|
| author | Jiqing Xu Fred de Winter Catherine Farrokhi Edward Rockenstein Michael Mante Anthony Adame Jonathan Cook Xin Jin Eliezer Masliah Kuo-Fen Lee |
| author_facet | Jiqing Xu Fred de Winter Catherine Farrokhi Edward Rockenstein Michael Mante Anthony Adame Jonathan Cook Xin Jin Eliezer Masliah Kuo-Fen Lee |
| author_sort | Jiqing Xu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a997ae6afef24fe08cc6ced631e49c4e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2016-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-a997ae6afef24fe08cc6ced631e49c4e2025-01-26T12:35:24ZengNature PortfolioScientific Reports2045-23222016-08-01611910.1038/srep31692Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease modelJiqing Xu0Fred de Winter1Catherine Farrokhi2Edward Rockenstein3Michael Mante4Anthony Adame5Jonathan Cook6Xin Jin7Eliezer Masliah8Kuo-Fen Lee9Clayton Foundation for Peptide Biology Laboratories, The Salk InstituteClayton Foundation for Peptide Biology Laboratories, The Salk InstituteClayton Foundation for Peptide Biology Laboratories, The Salk InstituteDepartment of Neurosciences, University of California at San DiegoDepartment of Neurosciences, University of California at San DiegoDepartment of Neurosciences, University of California at San DiegoMolecular Neurobiology Laboratories, The Salk InstituteMolecular Neurobiology Laboratories, The Salk InstituteDepartment of Neurosciences, University of California at San DiegoClayton Foundation for Peptide Biology Laboratories, The Salk InstituteAbstract 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.https://doi.org/10.1038/srep31692 |
| spellingShingle | Jiqing Xu Fred de Winter Catherine Farrokhi Edward Rockenstein Michael Mante Anthony Adame Jonathan Cook Xin Jin Eliezer Masliah Kuo-Fen Lee Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/srep31692 |
| work_keys_str_mv | AT jiqingxu neuregulin1improvescognitivedeficitsandneuropathologyinanalzheimersdiseasemodel AT freddewinter neuregulin1improvescognitivedeficitsandneuropathologyinanalzheimersdiseasemodel AT catherinefarrokhi neuregulin1improvescognitivedeficitsandneuropathologyinanalzheimersdiseasemodel AT edwardrockenstein neuregulin1improvescognitivedeficitsandneuropathologyinanalzheimersdiseasemodel AT michaelmante neuregulin1improvescognitivedeficitsandneuropathologyinanalzheimersdiseasemodel AT anthonyadame neuregulin1improvescognitivedeficitsandneuropathologyinanalzheimersdiseasemodel AT jonathancook neuregulin1improvescognitivedeficitsandneuropathologyinanalzheimersdiseasemodel AT xinjin neuregulin1improvescognitivedeficitsandneuropathologyinanalzheimersdiseasemodel AT eliezermasliah neuregulin1improvescognitivedeficitsandneuropathologyinanalzheimersdiseasemodel AT kuofenlee neuregulin1improvescognitivedeficitsandneuropathologyinanalzheimersdiseasemodel |