{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:20:37Z","timestamp":1792070437684,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2010,9,17]],"date-time":"2010-09-17T00:00:00Z","timestamp":1284681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Repair of myelin injury in multiple sclerosis may fail, resulting in chronic demyelination, axonal loss, and disease progression. As cellular pathways regulated by phosphatase and tensin homologue deleted on chromosome 10\n                      <jats:italic>(PTEN;<\/jats:italic>\n                      eg, phosphatidylinositol\u20103\u2010kinase [PI\u20103K]) have been reported to enhance axon regeneration and oligodendrocyte maturation, we investigated potentially beneficial effects of\n                      <jats:italic>Pten<\/jats:italic>\n                      loss of function in the oligodendrocyte lineage on remyelination.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We characterized oligodendrocyte numbers and myelin sheath thickness in mice with conditional inactivation of\n                      <jats:italic>Pten<\/jats:italic>\n                      in oligodendrocytes,\n                      <jats:italic>Olig2\u2010cre, Pten<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>fl\/fl<\/jats:italic>\n                      <\/jats:sup>\n                      mice. Using a model of central nervous system demyelination, lysolecithin injection into the spinal cord white matter, we performed short\u2010 and long\u2010term lesioning experiments and quantified oligodendrocyte maturation and myelin sheath thickness in remyelinating lesions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During development, we observed dramatic hypermyelination in the corpus callosum and spinal cord. Following white matter injury, however, there was no detectable improvement in remyelination. Moreover, we observed progressive myelin sheath abnormalities and massive axon degeneration in the fasciculus gracilis of mutant animals, as indicated by ultrastructure and expression of SMI\u201032, amyloid precursor protein, and caspase 6.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      These studies indicate adverse effects of chronic\n                      <jats:italic>Pten<\/jats:italic>\n                      inactivation (and by extension, activation PI\u20103K signaling) on myelinating oligodendrocytes and their axonal targets. We conclude that PTEN function in oligodendrocytes is required to regulate myelin thickness and preserve axon integrity. In contrast, PTEN is dispensable during myelin repair, and its inactivation confers no detectable benefit. Ann Neurol 2010\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.22090","type":"journal-article","created":{"date-parts":[[2010,9,17]],"date-time":"2010-09-17T15:58:29Z","timestamp":1284739109000},"page":"703-716","source":"Crossref","is-referenced-by-count":152,"title":["Oligodendrocyte\n                    <i>PTEN<\/i>\n                    is required for myelin and axonal integrity, not remyelination"],"prefix":"10.1002","volume":"68","author":[{"given":"Emily P.","family":"Harrington","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P. J.","family":"Fancy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sovann","family":"Kaing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J. M.","family":"Franklin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Rowitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,9,17]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.30.051606.094309"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2007.00107.x"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70161-5"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl217"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/280395a0"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn080"},{"issue":"8","key":"e_1_2_7_8_2","first-page":"1469","article-title":"Axonal damage correlates with disability in patients with relapsing\u2010remitting multiple sclerosis","volume":"121","author":"De Stefano N","year":"1998","journal-title":"Results of a longitudinal magnetic resonance spectroscopy study. 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