دورية أكاديمية
Mammalian target of rapamycin promotes oligodendrocyte differentiation, initiation and extent of CNS myelination.
| العنوان: | Mammalian target of rapamycin promotes oligodendrocyte differentiation, initiation and extent of CNS myelination. |
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| المؤلفون: | Wahl SE; Department of Neurology and Neuroscience, New Jersey Medical School Cancer Center, Rutgers Biomedical and Health Sciences, Newark, New Jersey 07103, and Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado 80045., McLane LE, Bercury KK, Macklin WB, Wood TL |
| المصدر: | The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2014 Mar 26; Vol. 34 (13), pp. 4453-65. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Print Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington, DC : Society for Neuroscience Original Publication: [Baltimore, Md.] : The Society, c1981- |
| مواضيع طبية MeSH: | Cell Differentiation/*genetics , Central Nervous System/*cytology , Gene Expression Regulation, Developmental/*physiology , Myelin Sheath/*metabolism , Oligodendroglia/*metabolism , TOR Serine-Threonine Kinases/*physiology, 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase/genetics ; Age Factors ; Animals ; Animals, Newborn ; Cell Count ; Central Nervous System/growth & development ; Female ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; In Vitro Techniques ; Integrases/genetics ; Integrases/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Myelin Proteins/metabolism ; Myelin Sheath/ultrastructure ; Oligodendroglia/ultrastructure ; TOR Serine-Threonine Kinases/deficiency ; TOR Serine-Threonine Kinases/genetics |
| مستخلص: | Prior studies support a role for mammalian target of rapamycin (mTOR) signaling in oligodendrocyte differentiation and myelination. Here we use Cre-recombinase driven by the CNP promoter to generate a mouse line with oligodendrocyte-specific knockdown of mTOR (mTOR cKO) in the CNS. We provide evidence that mTOR is necessary for proper oligodendrocyte differentiation and myelination in the spinal cord. Specifically, the number of mature oligodendrocytes was reduced, and the initiation and extent of myelination were impaired during spinal cord development. Consistent with these data, myelin protein expression, including myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein, and myelin-associated glycoprotein, was delayed in the spinal cord. Hypomyelination of the spinal cord persisted into adulthood, as did the reduction in numbers of mature oligodendrocytes. In the cortex, the structure of myelin appeared normal during development and in the adult; however, myelin protein expression was delayed during development and was abnormal in the adult. Myelin basic protein was significantly reduced in all regions at postnatal day 25. These data demonstrate that mTOR promotes oligodendrocyte differentiation and CNS myelination in vivo and show that the requirement for mTOR varies by region with the spinal cord most dependent on mTOR. |
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| معلومات مُعتمدة: | NS082203 United States NS NINDS NIH HHS; R01 NS082203 United States NS NINDS NIH HHS; F31 NS076187 United States NS NINDS NIH HHS; NS076187 United States NS NINDS NIH HHS; R37 NS082203 United States NS NINDS NIH HHS |
| فهرسة مساهمة: | Keywords: differentiation; mTOR; myelination; oligodendrocyte; signaling |
| المشرفين على المادة: | 0 (Myelin Proteins) 147336-22-9 (Green Fluorescent Proteins) EC 2.7.1.1 (mTOR protein, mouse) EC 2.7.11.1 (TOR Serine-Threonine Kinases) EC 2.7.7.- (Cre recombinase) EC 2.7.7.- (Integrases) EC 3.1.4.37 (2',3'-Cyclic Nucleotide 3'-Phosphodiesterase) EC 3.1.4.37 (Cnp protein, mouse) |
| تواريخ الأحداث: | Date Created: 20140328 Date Completed: 20140519 Latest Revision: 20220309 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC3965776 |
| DOI: | 10.1523/JNEUROSCI.4311-13.2014 |
| PMID: | 24671992 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1529-2401 |
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| DOI: | 10.1523/JNEUROSCI.4311-13.2014 |