<i>In Vivo</i> Expression of Reprogramming Factor OCT4 Ameliorates Myelination Deficits and Induces Striatal Neuroprotection in Huntington’s Disease
White matter atrophy has been shown to precede the massive loss of striatal GABAergic neurons in Huntington’s disease (HD). This study investigated the effects of <i>in vivo</i> expression of reprogramming factor octamer-binding transcription factor 4 (OCT4) on neural stem cell (NSC) nic...
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MDPI AG
2021-05-01
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| Online Access: | https://www.mdpi.com/2073-4425/12/5/712 |
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| author | Ji-Hea Yu Bae-Geun Nam Min-Gi Kim Soonil Pyo Jung-Hwa Seo Sung-Rae Cho |
| author_facet | Ji-Hea Yu Bae-Geun Nam Min-Gi Kim Soonil Pyo Jung-Hwa Seo Sung-Rae Cho |
| author_sort | Ji-Hea Yu |
| collection | DOAJ |
| description | White matter atrophy has been shown to precede the massive loss of striatal GABAergic neurons in Huntington’s disease (HD). This study investigated the effects of <i>in vivo</i> expression of reprogramming factor octamer-binding transcription factor 4 (OCT4) on neural stem cell (NSC) niche activation in the subventricular zone (SVZ) and induction of cell fate specific to the microenvironment of HD. R6/2 mice randomly received adeno-associated virus 9 (AAV9)-OCT4, AAV9-Null, or phosphate-buffered saline into both lateral ventricles at 4 weeks of age. The AAV9-OCT4 group displayed significantly improved behavioral performance compared to the control groups. Following AAV9-OCT4 treatment, the number of newly generated NSCs and oligodendrocyte progenitor cells (OPCs) significantly increased in the SVZ, and the expression of OPC-related genes and glial cell-derived neurotrophic factor (GDNF) significantly increased. Further, amelioration of myelination deficits in the corpus callosum was observed through electron microscopy and magnetic resonance imaging, and striatal DARPP32<sup>+</sup> GABAergic neurons significantly increased in the AAV9-OCT4 group. These results suggest that <i>in situ</i> expression of the reprogramming factor OCT4 in the SVZ induces OPC proliferation, thereby attenuating myelination deficits. Particularly, GDNF released by OPCs seems to induce striatal neuroprotection in HD, which explains the behavioral improvement in R6/2 mice overexpressing OCT4. |
| first_indexed | 2024-03-10T11:33:58Z |
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| id | doaj.art-b43f51a92774428fae8aeb8cde063811 |
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| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T11:33:58Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
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| series | Genes |
| spelling | doaj.art-b43f51a92774428fae8aeb8cde0638112023-11-21T19:02:54ZengMDPI AGGenes2073-44252021-05-0112571210.3390/genes12050712<i>In Vivo</i> Expression of Reprogramming Factor OCT4 Ameliorates Myelination Deficits and Induces Striatal Neuroprotection in Huntington’s DiseaseJi-Hea Yu0Bae-Geun Nam1Min-Gi Kim2Soonil Pyo3Jung-Hwa Seo4Sung-Rae Cho5Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, KoreaBrain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, KoreaWhite matter atrophy has been shown to precede the massive loss of striatal GABAergic neurons in Huntington’s disease (HD). This study investigated the effects of <i>in vivo</i> expression of reprogramming factor octamer-binding transcription factor 4 (OCT4) on neural stem cell (NSC) niche activation in the subventricular zone (SVZ) and induction of cell fate specific to the microenvironment of HD. R6/2 mice randomly received adeno-associated virus 9 (AAV9)-OCT4, AAV9-Null, or phosphate-buffered saline into both lateral ventricles at 4 weeks of age. The AAV9-OCT4 group displayed significantly improved behavioral performance compared to the control groups. Following AAV9-OCT4 treatment, the number of newly generated NSCs and oligodendrocyte progenitor cells (OPCs) significantly increased in the SVZ, and the expression of OPC-related genes and glial cell-derived neurotrophic factor (GDNF) significantly increased. Further, amelioration of myelination deficits in the corpus callosum was observed through electron microscopy and magnetic resonance imaging, and striatal DARPP32<sup>+</sup> GABAergic neurons significantly increased in the AAV9-OCT4 group. These results suggest that <i>in situ</i> expression of the reprogramming factor OCT4 in the SVZ induces OPC proliferation, thereby attenuating myelination deficits. Particularly, GDNF released by OPCs seems to induce striatal neuroprotection in HD, which explains the behavioral improvement in R6/2 mice overexpressing OCT4.https://www.mdpi.com/2073-4425/12/5/712Huntington’s diseasereprogrammingoctamer-binding transcription factor 4oligodendrocyte progenitor cells |
| spellingShingle | Ji-Hea Yu Bae-Geun Nam Min-Gi Kim Soonil Pyo Jung-Hwa Seo Sung-Rae Cho <i>In Vivo</i> Expression of Reprogramming Factor OCT4 Ameliorates Myelination Deficits and Induces Striatal Neuroprotection in Huntington’s Disease Genes Huntington’s disease reprogramming octamer-binding transcription factor 4 oligodendrocyte progenitor cells |
| title | <i>In Vivo</i> Expression of Reprogramming Factor OCT4 Ameliorates Myelination Deficits and Induces Striatal Neuroprotection in Huntington’s Disease |
| title_full | <i>In Vivo</i> Expression of Reprogramming Factor OCT4 Ameliorates Myelination Deficits and Induces Striatal Neuroprotection in Huntington’s Disease |
| title_fullStr | <i>In Vivo</i> Expression of Reprogramming Factor OCT4 Ameliorates Myelination Deficits and Induces Striatal Neuroprotection in Huntington’s Disease |
| title_full_unstemmed | <i>In Vivo</i> Expression of Reprogramming Factor OCT4 Ameliorates Myelination Deficits and Induces Striatal Neuroprotection in Huntington’s Disease |
| title_short | <i>In Vivo</i> Expression of Reprogramming Factor OCT4 Ameliorates Myelination Deficits and Induces Striatal Neuroprotection in Huntington’s Disease |
| title_sort | i in vivo i expression of reprogramming factor oct4 ameliorates myelination deficits and induces striatal neuroprotection in huntington s disease |
| topic | Huntington’s disease reprogramming octamer-binding transcription factor 4 oligodendrocyte progenitor cells |
| url | https://www.mdpi.com/2073-4425/12/5/712 |
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