Ndufs4 ablation decreases synaptophysin expression in hippocampus

Abstract Altered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, t...

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Autores principales: Subrata Kumar Shil, Yoshiteru Kagawa, Banlanjo Abdulaziz Umaru, Fumika Nanto-Hara, Hirofumi Miyazaki, Yui Yamamoto, Shuhei Kobayashi, Chitose Suzuki, Takaaki Abe, Yuji Owada
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/2f1ecd6aa88a4dd3b49f22c37b7181ca
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spelling oai:doaj.org-article:2f1ecd6aa88a4dd3b49f22c37b7181ca2021-12-02T16:53:10ZNdufs4 ablation decreases synaptophysin expression in hippocampus10.1038/s41598-021-90127-42045-2322https://doaj.org/article/2f1ecd6aa88a4dd3b49f22c37b7181ca2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90127-4https://doaj.org/toc/2045-2322Abstract Altered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.Subrata Kumar ShilYoshiteru KagawaBanlanjo Abdulaziz UmaruFumika Nanto-HaraHirofumi MiyazakiYui YamamotoShuhei KobayashiChitose SuzukiTakaaki AbeYuji OwadaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Subrata Kumar Shil
Yoshiteru Kagawa
Banlanjo Abdulaziz Umaru
Fumika Nanto-Hara
Hirofumi Miyazaki
Yui Yamamoto
Shuhei Kobayashi
Chitose Suzuki
Takaaki Abe
Yuji Owada
Ndufs4 ablation decreases synaptophysin expression in hippocampus
description Abstract Altered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.
format article
author Subrata Kumar Shil
Yoshiteru Kagawa
Banlanjo Abdulaziz Umaru
Fumika Nanto-Hara
Hirofumi Miyazaki
Yui Yamamoto
Shuhei Kobayashi
Chitose Suzuki
Takaaki Abe
Yuji Owada
author_facet Subrata Kumar Shil
Yoshiteru Kagawa
Banlanjo Abdulaziz Umaru
Fumika Nanto-Hara
Hirofumi Miyazaki
Yui Yamamoto
Shuhei Kobayashi
Chitose Suzuki
Takaaki Abe
Yuji Owada
author_sort Subrata Kumar Shil
title Ndufs4 ablation decreases synaptophysin expression in hippocampus
title_short Ndufs4 ablation decreases synaptophysin expression in hippocampus
title_full Ndufs4 ablation decreases synaptophysin expression in hippocampus
title_fullStr Ndufs4 ablation decreases synaptophysin expression in hippocampus
title_full_unstemmed Ndufs4 ablation decreases synaptophysin expression in hippocampus
title_sort ndufs4 ablation decreases synaptophysin expression in hippocampus
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/2f1ecd6aa88a4dd3b49f22c37b7181ca
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