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Background
Activin A (Act A) has been revealed to enhance the differentiation of oligodendrocyte progenitor cells (OPCs) in vitro. Here we aim to elucidate its roles and mechanisms in a rat model of white matter injury (WMI).
Methods
Act A was injected into the lateral ventricle of a hypoxia-ischemia induced WMI rat model. Hematoxylin & eosin staining was used to detect pathological changes. Immunofluorescence staining was used to assess OPC proliferation, migration, apoptosis, and differentiation. Myelin sheath and axon formation were detected via immunofluorescence staining, Western blotting, and electron microscopy. Behavioral assessment of rats was performed with the Morris water maze test.
Results
Act A attenuated the pathological damages, enhanced the formation of myelin sheath and myelinated axons and improved the behavior of WMI rats by promoting OPC proliferation and differentiation. However, Act A showed no significant effects on OPC migration or apoptosis. Interestingly, we found that Act A could enhance Noggin expression, which in turn inhibited the expression of bone morphogenetic protein 4 (BMP4) and inhibitor of DNA binding 2 (Id2). Furthermore, upregulation of Id2 completely abolished the protective effects of Act A in WMI.
Conclusions
Act A improves WMI in neonatal rats via Noggin/BMP4/Id2 signalling.
Keywords
Activin A, Noggin/BMP4/Id2 signalling, myelination, oligodendrocyte progenitor cells, white matter injury
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 08 Jun, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Activin A (Act A) has been revealed to enhance the differentiation of oligodendrocyte progenitor cells (OPCs) in vitro. Here we aim to elucidate its roles and mechanisms in a rat model of white matter injury (WMI).
Methods
Act A was injected into the lateral ventricle of a hypoxia-ischemia induced WMI rat model. Hematoxylin & eosin staining was used to detect pathological changes. Immunofluorescence staining was used to assess OPC proliferation, migration, apoptosis, and differentiation. Myelin sheath and axon formation were detected via immunofluorescence staining, Western blotting, and electron microscopy. Behavioral assessment of rats was performed with the Morris water maze test.
Results
Act A attenuated the pathological damages, enhanced the formation of myelin sheath and myelinated axons and improved the behavior of WMI rats by promoting OPC proliferation and differentiation. However, Act A showed no significant effects on OPC migration or apoptosis. Interestingly, we found that Act A could enhance Noggin expression, which in turn inhibited the expression of bone morphogenetic protein 4 (BMP4) and inhibitor of DNA binding 2 (Id2). Furthermore, upregulation of Id2 completely abolished the protective effects of Act A in WMI.
Conclusions
Act A improves WMI in neonatal rats via Noggin/BMP4/Id2 signalling.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
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