{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:24:30Z","timestamp":1772252670221,"version":"3.50.1"},"reference-count":82,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T00:00:00Z","timestamp":1620604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Research Foundation of Korea","award":["2019R1I1A1A01057970"],"award-info":[{"award-number":["2019R1I1A1A01057970"]}]},{"name":"the Ministry of Health &amp; Welfare, Republic of Korea","award":["HI16C1012"],"award-info":[{"award-number":["HI16C1012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>White matter atrophy has been shown to precede the massive loss of striatal GABAergic neurons in Huntington\u2019s disease (HD). This study investigated the effects of in vivo 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+ GABAergic neurons significantly increased in the AAV9-OCT4 group. These results suggest that in situ 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.<\/jats:p>","DOI":"10.3390\/genes12050712","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T12:49:49Z","timestamp":1620650989000},"page":"712","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["In Vivo Expression of Reprogramming Factor OCT4 Ameliorates Myelination Deficits and Induces Striatal Neuroprotection in Huntington\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Ji-Hea","family":"Yu","sequence":"first","affiliation":[{"name":"Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4535-5684","authenticated-orcid":false,"given":"Bae-Geun","family":"Nam","sequence":"additional","affiliation":[{"name":"Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Graduate Program of Nano Science and Technology, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6921-3085","authenticated-orcid":false,"given":"Min-Gi","family":"Kim","sequence":"additional","affiliation":[{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soonil","family":"Pyo","sequence":"additional","affiliation":[{"name":"Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8489-7972","authenticated-orcid":false,"given":"Jung-Hwa","family":"Seo","sequence":"additional","affiliation":[{"name":"Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1429-2684","authenticated-orcid":false,"given":"Sung-Rae","family":"Cho","sequence":"additional","affiliation":[{"name":"Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, Korea"},{"name":"Graduate Program of Nano Science and Technology, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.biopsych.2017.10.019","article-title":"Brain regions showing white matter loss in huntington\u2019s disease are enriched for synaptic and metabolic genes","volume":"83","author":"McColgan","year":"2018","journal-title":"Biol. 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