{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:24:03Z","timestamp":1787027043953,"version":"build-2736575974"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018621","name":"Program for Changjiang Scholars and Innovative Research Team in University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013317","name":"Shanxi Provincial Key Research and Development Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013317","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Preterm white matter injury (PWMI) is the most common form of brain damage in premature infants caused by hypoxia-ischemia (HI), inflammation, or excitotoxicity. It is characterized by oligodendrocyte precursor cell (OPC) differentiation disorder and dysmyelination. Our previous study confirmed that alpha-asarone (\u03b1-asaronol), a major compound isolated from the Chinese medicinal herb\n                    <jats:italic>Acorus gramineus<\/jats:italic>\n                    by our lab, could alleviate neuronal overexcitation and improve the cognitive function of aged rats. In the present study, we investigated the effect and mechanism of \u03b1-asaronol on myelination in a rat model of PWMI induced by HI. Notably, \u03b1-asaronol promoted OPC differentiation and myelination in the corpus callosum of PWMI rats. Meanwhile, the concentration of glutamate was significantly decreased, and the levels of PPAR\u03b3 and glutamate transporter 1 (GLT-1) were increased by \u03b1-asaronol treatment.\n                    <jats:italic>In vitro,<\/jats:italic>\n                    it was also confirmed that \u03b1-asaronol increased GLT-1 expression and recruitment of the PPAR\u03b3 coactivator PCG-1a in astrocytes under oxygen and glucose deprivation (OGD) conditions. The PPAR\u03b3 inhibitor GW9662 significantly reversed the effect of \u03b1-asaronol on GLT-1 expression and PCG-1a recruitment. Interestingly, the conditioned medium from \u03b1-asaronol-treated astrocytes decreased the number of OPCs and increased the number of mature oligodendrocytes. These results suggest that \u03b1-asaronol can promote OPC differentiation and relieve dysmyelination by regulating glutamate levels\n                    <jats:italic>via<\/jats:italic>\n                    astrocyte PPAR\u03b3-GLT-1 signaling. Although whether\n                    <jats:italic>\u03b1<\/jats:italic>\n                    -asaronol binds to PPAR\u03b3 directly or indirectly is not investigated here, this study still indicates that\n                    <jats:italic>\u03b1<\/jats:italic>\n                    -asaronol may be a promising small molecular drug for the treatment of myelin-related diseases.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.766744","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T18:40:18Z","timestamp":1648492818000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Alpha-Asaronol Alleviates Dysmyelination by Enhancing Glutamate Transport Through the Activation of PPAR\u03b3-GLT-1 Signaling in Hypoxia-Ischemia Neonatal Rats"],"prefix":"10.3389","volume":"13","author":[{"given":"Yuhang","family":"Ge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zhen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaowei","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqin","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/sj.jcbfm.9600344","article-title":"Hypoxia-ischemia Preferentially Triggers Glutamate Depletion from Oligodendroglia and Axons in Perinatal Cerebral white Matter","volume":"27","author":"Back","year":"2007","journal-title":"J. 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