Enhancing Oligodendrocyte Myelination Rescues Synaptic Loss and Improves Functional Recovery after Chronic Hypoxia
| Autor: | Jun Zhang, Stephen P.J. Fancy, Jonah R. Chan, Nian Yang, Feng Mei, Yi Wu, Xing Gao, Lan Xiao, Guang-Qiang Pan, Nan-Xing Huang, Yu-Jian Yang, Fei Wang, Hongli Li, Shubao Liu, Xianjun Chen, Zhi Liu, Tao Li |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male hypomyelination Synaptogenesis clemastine Inbred C57BL Low Birth Weight and Health of the Newborn Transgenic Mice 0302 clinical medicine Muscarinic acetylcholine receptor Infant Mortality U-50488 Psychology Hypoxia Myelin Sheath Pediatric synaptogenesis General Neuroscience Neurogenesis Rehabilitation vGlut1 Oligodendroglia medicine.anatomical_structure Olig2 Neurological Excitatory postsynaptic potential Female Cognitive Sciences medicine.symptom Receptor M1R Mice Transgenic Biology Article OLIG2 03 medical and health sciences Preterm medicine Animals kappa opioid receptor Neurology & Neurosurgery Receptor Muscarinic M1 Oligodendrocyte differentiation Neurosciences Recovery of Function Hypoxia (medical) Perinatal Period - Conditions Originating in Perinatal Period Newborn Oligodendrocyte Brain Disorders Mice Inbred C57BL 030104 developmental biology Animals Newborn Muscarinic M1 Synapses Chronic Disease white matter injury beam-walking test Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuron, vol 99, iss 4 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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