Growth hormone promotes myelin repair after chronic hypoxia via triggering pericyte-dependent angiogenesis.
- Resource Type
- Academic Journal
- Authors
- Ren SY; Department of Histology and Embryology, Chongqing Key Laboratory of Brain Development and Cognition, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Xia Y; Department of Histology and Embryology, Chongqing Key Laboratory of Brain Development and Cognition, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Yu B; Department of Histology and Embryology, Chongqing Key Laboratory of Brain Development and Cognition, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing 400038, China; Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Lei QJ; Department of Histology and Embryology, Chongqing Key Laboratory of Brain Development and Cognition, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Hou PF; Department of Histology and Embryology, Chongqing Key Laboratory of Brain Development and Cognition, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Guo S; Department of Immunology, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Wu SL; Department of Histology and Embryology, Chongqing Key Laboratory of Brain Development and Cognition, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Liu W; Department of Histology and Embryology, Chongqing Key Laboratory of Brain Development and Cognition, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Yang SF; Brain Research Center, State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Jiang YB; Department of Neurobiology, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Chen JF; Department of Histology and Embryology, Chongqing Key Laboratory of Brain Development and Cognition, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Shen KF; Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Zhang CQ; Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Wang F; Department of Histology and Embryology, Chongqing Key Laboratory of Brain Development and Cognition, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Yan M; Department of Pediatrics, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing 400000, China.; Ren H; Department of Emergence, 5(th) People's Hospital of Chongqing, Chongqing 400062, China.; Yang N; Department of Physiology, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Zhang J; Department of Neurobiology, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Zhang K; Brain Research Center, State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Lin S; Department of Neurology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Li T; Department of Histology and Embryology, Chongqing Key Laboratory of Brain Development and Cognition, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Yang QW; Department of Neurology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Xiao L; Department of Histology and Embryology, Chongqing Key Laboratory of Brain Development and Cognition, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Hu ZX; Department of Pediatrics, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing 400000, China. Electronic address: huzhangxue@tmmu.edu.cn.; Mei F; Department of Histology and Embryology, Chongqing Key Laboratory of Brain Development and Cognition, Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Third Military Medical University (Army Medical University), Chongqing 400038, China. Electronic address: meif@tmmu.edu.cn.
- Source
- Publisher: Cell Press Country of Publication: United States NLM ID: 8809320 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4199 (Electronic) Linking ISSN: 08966273 NLM ISO Abbreviation: Neuron Subsets: MEDLINE
- Subject
- Language
- English
White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI.
Competing Interests: Declaration of interests The authors declare no competing interests.
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