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Oligodendrocyte responses to stresses

少突胶质细胞对压力的反应

基本信息

批准号：
10328919
负责人：
WENDY B MACKLIN
金额：
$ 37.41万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10328919
关键词：
Adolescent Adult Antioxidants Automobile Driving Axon Blood Vessels Brain Cell Differentiation process Cells Cerebrum Cessation of life Cicatrix Corpus striatum structure Data Development Disease Exhibits Growth Factor IGF1R gene Injury Ischemia Life Mediating Metabolic Middle Cerebral Artery Occlusion Modeling Multiple Sclerosis Mus Myelin Nervous system structure Neuraxis Neuroglia Neurologic Neurons Oligodendroglia Pathology Pathway interactions Periventricular Leukomalacia Play Proteins RNA Reactive Oxygen Species Recovery of Function Reperfusion Injury Reperfusion Therapy Resistance Role Signal Pathway Signal Transduction Somatomedins Stress Testing Tissues Transgenic Mice autocrine brain tissue ischemic injury myelination nervous system development nervous system disorder oligodendrocyte progenitor perinatal period preservation resilience response stem cells transcription factor

项目摘要

Project Summary Myelination is essential for normal nervous system development, and the juvenile period is a major period of myelination. Differentiation of the oligodendrocyte, the myelinating cell of the CNS, is tightly regulated, and disruption of oligodendrocyte development leads to neurologic problems, such as periventricular leukomalacia and retardation. How injury during this period impacts myelination is poorly understood, although ischemic damage in the perinatal period or adults damages oligodendrocytes along with other cells, driving major tissue damage. We initiated studies to investigate the impact of juvenile ischemia on CNS myelination, as this period has distinctly different metabolic demands. We found that despite extensive death of striatal neurons, oligodendrocytes and myelinated axons were remarkably preserved in the juvenile brain, in stark contrast to the adult which exhibits extensive oligodendrocyte and myelin injury (Ahrendsen et al., Glia 64:1972, 2016). Quite intriguingly, in addition to oligodendrocyte resistance to ischemic injury in the actively myelinating juvenile brain, a transgenic mouse line that continues active myelination throughout life also has relatively protected oligodendrocytes. In the proposed studies, we will test the hypotheses that actively myelinating oligodendrocytes have high levels of anti-oxidant pathway molecules that protect them from ischemic damage, and that such damage increases their expression of insulin-like growth factor (IGF-1), which acts in an autocrine m manner to additionally protect myelinating oligodendrocytes. We have three related specific aims that test these hypotheses by investigating 1) the role of the Nrf2 signaling pathway in actively myelinating oligodendrocytes in response to ischemia; 2) the role of IGF-1 in protection of actively myelinating oligodendrocytes; and 3) the role of IGF-1 signaling in conjunction with reactive oxygen species in driving oligodendrocyte progenitor cell differentiation.

项目总结