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      Epigenetic Mechanisms Underlying Adult Post Stroke Neurogenesis

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          Abstract

          Stroke remains the leading cause of adult disability. Post-stroke neurogenesis contributes to functional recovery. As an intrinsic neurorestorative process, it is important to elucidate the molecular mechanism underlying stroke-induced neurogenesis and to develop therapies designed specifically to augment neurogenesis. Epigenetic mechanisms include DNA methylation, histone modification and its mediation by microRNAs and long-non-coding RNAs. In this review, we highlight how epigenetic factors including DNA methylation, histone modification, microRNAs and long-non-coding RNAs mediate stroke-induced neurogenesis including neural stem cell self-renewal and cell fate determination. We also summarize therapies targeting these mechanisms in the treatment of stroke.

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          Neuronal replacement from endogenous precursors in the adult brain after stroke.

          Andreas Arvidsson, Tove Collin, Deniz Kirik … (2002)
          In the adult brain, new neurons are continuously generated in the subventricular zone and dentate gyrus, but it is unknown whether these neurons can replace those lost following damage or disease. Here we show that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the severely damaged area of the striatum, where they express markers of developing and mature, striatal medium-sized spiny neurons. Thus, stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion. Here we show that the adult brain has the capacity for self-repair after insults causing extensive neuronal death. If the new neurons are functional and their formation can be stimulated, a novel therapeutic strategy might be developed for stroke in humans.
          Article 0 comments Cited 609 times – based on 0 reviews     Review now
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            Exosome Mediated Delivery of miR-124 Promotes Neurogenesis after Ischemia

            Jialei Yang, Xiufen Zhang, Xiangjie Chen … (2017)
            The intrinsic ability of neurogenesis after stroke has been proven weak, which results in insufficient repair of injury in the nerve system. Recent studies suggest multiple microRNAs (miRNAs) are involved in the neuroremodeling process. Targeted miRNAs delivery for amplification of neurogenesis is promising in promoting the prognosis after ischemia. Here, we showed that modified exosomes, with rabies virus glycoprotein (RVG) fused to exosomal protein lysosome-associated membrane glycoprotein 2b (Lamp2b), could efficiently deliver miR-124 to the infarct site. Systemic administration of RVG-exosomes loaded with miR-124 promoted cortical neural progenitors to obtain neuronal identity and protect against ischemic injury by robust cortical neurogenesis. Our study suggests that RVG-exosomes can be utilized therapeutically for the targeted delivery of gene drugs to the brain, thus having great potential for clinical applications.
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              Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone.

              M B Luskin (1993)
              The subventricular zone of the postnatal forebrain produces mainly glia, although it supports limited neurogenesis. To determine whether the subventricular zone is positionally specified, the phenotype and destination of the progeny of subventricular zone cells along the anterior-posterior axis of the lateral ventricles were analyzed. A retroviral lineage tracer containing the E. coli reporter gene lacZ was injected into different parts of the subventricular zone of neonatal rat pups, and at various times thereafter, the expression of beta-galactosidase was detected histochemically or immunohistochemically in the descendants of infected cells. A discrete region of the anterior part of the subventricular zone (SVZa) generated an immense number of neurons that differentiated into granule cells and periglomerular cells of the olfactory bulb-the two major types of interneurons. Thus, the SVZa appears to constitute a specialized source of neuronal progenitor cells. To reach the olfactory bulb, neurons arising in the SVZa migrate several millimeters along a highly restricted route. Guidance cues must be involved to prohibit widespread dispersion of these migrating neurons.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 27 August 2020
                Publication date Collection: September 2020
                Volume: 21
                Issue: 17
                Electronic Location Identifier: 6179
                Affiliations
                [1 ]Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA; bfan1@ 123456hfhs.org (B.F.); mchopp1@ 123456hfhs.org (M.C.); zzhang1@ 123456hfhs.org (Z.Z.)
                [2 ]Department of Physics, Oakland University, Rochester, MI 48309, USA
                Author notes
                [* ]Correspondence: xliu2@ 123456hfhs.org ; Tel.: +1-313-916-5995
                Author information
                https://orcid.org/0000-0003-2414-321X
                https://orcid.org/0000-0001-8077-8039
                Article
                Publisher ID: ijms-21-06179
                DOI: 10.3390/ijms21176179
                PMC ID: 7504398
                PubMed ID: 32867041
                SO-VID: 9c0c9132-3bf5-43a0-8dd5-83995d514108
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 23 July 2020
                Date accepted : 25 August 2020
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: stroke,epigenetics,micrornas,histone deacetylation,adult neurogenesis,long non-coding rna
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: stroke, epigenetics, micrornas, histone deacetylation, adult neurogenesis, long non-coding rna

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