Activin A Improves White Matter Injury in Neonatal Rats via Noggin/bmp4/id2 Signaling release_mpgznbi2qvdlzc224nin3b7uyq

Abstract

<jats:title>Abstract</jats:title> BackgroundActivin 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). MethodsAct A was injected into the lateral ventricle of a hypoxia-ischemia induced WMI rat model. Hematoxylin &amp; 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. ResultsAct 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. ConclusionsAct A improves WMI in neonatal rats via Noggin/BMP4/Id2 signalling.
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