Signaling by growth/differentiation factor 5 through the bone morphogenetic protein receptor type IB protects neurons against kainic acid-induced neurodegeneration
Copyright © 2017 Elsevier B.V. All rights reserved..
Growth/differentiation factor-5 (GDF-5), a member of the transforming growth factor-beta (TGF-β) superfamily, has been shown to protect rat dopaminergic neurons against insult both in embryonic neuronal culture and in Parkinson's disease models. However, whether GDF-5 exerts neuroprotective effects in hippocampal neurons is unclear. Here, we show that both mRNA levels and protein levels of GDF-5 are decreased in the mouse hippocampus upon kainic acid (KA) treatment. KA induced dramatic neuronal loss specifically in the cornu ammonis 1 (CA1) and CA3 areas of the mouse hippocampus, while intracerebral infusion of GDF-5 prevented this neuronal loss. The neuroprotective effects of GDF-5 were recapitulated by constitutively active bone morphogenetic protein type IB receptor (BMPRIB-CA) and could be blocked by BMPRI kinase inhibitor LDN-193189. Furthermore, the neuroprotective effects of GDF-5 were mediated through the prevention of apoptosis, which was indicated by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining and reduced cleaved caspase 3 expression level. Thus, we conclude that GDF-5 protects hippocampal neurons against KA-induced neurodegeneration by signaling through BMPRIB, suggesting a therapeutic potential for GDF-5 in neurodegenerative diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:651 |
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| Enthalten in: |
Neuroscience letters - 651(2017) vom: 09. Juni, Seite 36-42 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Yuanzheng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.03.2018 Date Revised 05.09.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.neulet.2017.04.055 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM271438649 |
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| 520 | |a Growth/differentiation factor-5 (GDF-5), a member of the transforming growth factor-beta (TGF-β) superfamily, has been shown to protect rat dopaminergic neurons against insult both in embryonic neuronal culture and in Parkinson's disease models. However, whether GDF-5 exerts neuroprotective effects in hippocampal neurons is unclear. Here, we show that both mRNA levels and protein levels of GDF-5 are decreased in the mouse hippocampus upon kainic acid (KA) treatment. KA induced dramatic neuronal loss specifically in the cornu ammonis 1 (CA1) and CA3 areas of the mouse hippocampus, while intracerebral infusion of GDF-5 prevented this neuronal loss. The neuroprotective effects of GDF-5 were recapitulated by constitutively active bone morphogenetic protein type IB receptor (BMPRIB-CA) and could be blocked by BMPRI kinase inhibitor LDN-193189. Furthermore, the neuroprotective effects of GDF-5 were mediated through the prevention of apoptosis, which was indicated by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining and reduced cleaved caspase 3 expression level. Thus, we conclude that GDF-5 protects hippocampal neurons against KA-induced neurodegeneration by signaling through BMPRIB, suggesting a therapeutic potential for GDF-5 in neurodegenerative diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Bone morphogenetic protein type IB receptor | |
| 650 | 4 | |a Growth/differentiation factor-5 | |
| 650 | 4 | |a Hippocampal neuron | |
| 650 | 4 | |a Kainic acid | |
| 650 | 4 | |a Neurodegenerative disease | |
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| 650 | 7 | |a Neuroprotective Agents |2 NLM | |
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| 650 | 7 | |a Bone Morphogenetic Protein Receptors, Type I |2 NLM | |
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| 700 | 1 | |a Zhang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hengfang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jianping |e verfasserin |4 aut | |
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