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Enhancing Oligodendrocyte Myelination Rescues Synaptic Loss and Improves Functional Recovery after Chronic Hypoxia.
Wang, Fei; Yang, Yu-Jian; Yang, Nian; Chen, Xian-Jun; Huang, Nan-Xin; Zhang, Jun; Wu, Yi; Liu, Zhi; Gao, Xing; Li, Tao; Pan, Guang-Qiang; Liu, Shu-Bao; Li, Hong-Li; Fancy, Stephen P J; Xiao, Lan; Chan, Jonah R; Mei, Feng.
Afiliación
  • Wang F; Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
  • Yang YJ; Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
  • Yang N; Department of Physiology, Third Military Medical University, Chongqing 400038, China.
  • Chen XJ; Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
  • Huang NX; Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
  • Zhang J; Department of Physiology, Third Military Medical University, Chongqing 400038, China.
  • Wu Y; Department of Digital Medicine, Biomedical Engineering College, Third Military Medical University, Chongqing 400038, China.
  • Liu Z; Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
  • Gao X; Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
  • Li T; Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
  • Pan GQ; Department of Pathology, Affiliated Xinqiao Hospital, Third Military Medical University, Chongqing 400038, China.
  • Liu SB; Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
  • Li HL; Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
  • Fancy SPJ; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Xiao L; Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China. Electronic address: xiaolan35@hotmail.com.
  • Chan JR; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: jonah.chan@ucsf.edu.
  • Mei F; Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China. Electronic address: meif@tmmu.edu.cn.
Neuron ; 99(4): 689-701.e5, 2018 08 22.
Article en En | MEDLINE | ID: mdl-30078577
To address the significance of enhancing myelination for functional recovery after white matter injury (WMI) in preterm infants, we characterized hypomyelination associated with chronic hypoxia and identified structural and functional deficits of excitatory cortical synapses with a prolonged motor deficit. We demonstrate that genetically delaying myelination phenocopies the synaptic and functional deficits observed in mice after hypoxia, suggesting that myelination may possibly facilitate excitatory presynaptic innervation. As a gain-of-function experiment, we specifically ablated the muscarinic receptor 1 (M1R), a negative regulator of oligodendrocyte differentiation in oligodendrocyte precursor cells. Genetically enhancing oligodendrocyte differentiation and myelination rescued the synaptic loss after chronic hypoxia and promoted functional recovery. As a proof of concept, drug-based myelination therapies also resulted in accelerated differentiation and myelination with functional recovery after chronic hypoxia. Together, our data indicate that myelination-enhancing strategies in preterm infants may represent a promising therapeutic approach for structural/functional recovery after hypoxic WMI.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Oligodendroglía / Recuperación de la Función / Neurogénesis / Hipoxia / Vaina de Mielina Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Oligodendroglía / Recuperación de la Función / Neurogénesis / Hipoxia / Vaina de Mielina Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos