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• W2326678049 abstract "Spinal muscular atrophy (SMA) is a genetic disorder characterized by loss of motor neurons in the spinal cord leading to muscle atrophy and death. Although motor neurons (MNs) are the most obviously affected cells in SMA, recent evidence suggest dysfunction in multiple cell types. Astrocytes are a crucial component of the motor circuit and are intimately involved with MN health and maintenance. We have previously shown that SMA astrocytes are altered both morphologically and functionally early in disease progression, though it is unclear what causes astrocytes to become reactive. Oxidative stress is a common feature among neurodegenerative diseases. Oxidative stress can both induce apoptosis in neurons and can cause astrocytes to become reactive, which are features observed in the SMA induced pluripotent stem cell (iPSC) cultures. Therefore, we asked if oxidative stress contributes to SMA astrocyte pathology. We examined mitochondrial bioenergetics, transcript and protein levels of oxidative and anti-oxidant factors, and reactive oxygen species (ROS) production and found little evidence of oxidative stress. We did observe a significant increase in endogenous catalase expression in SMA iPSCs. While catalase knockdown in SMA iPSCs increased ROS production above basal levels, levels of ROS remained lower than in controls, further arguing against robust oxidative stress in this system. Viral delivery of survival motor neuron (SMN) reversed astrocyte activation and restored catalase levels to normal, without changing mitochondrial respiration or expression of oxidative stress markers. Taken together, these data indicate that SMN deficiency induces astrocyte reactivity, but does not do so through an oxidative stress-mediated process." @default.
• W2326678049 created "2016-06-24" @default.
• W2326678049 creator A5031613698 @default.
• W2326678049 creator A5091428631 @default.
• W2326678049 date "2015-12-07" @default.
• W2326678049 modified "2023-10-16" @default.
• W2326678049 title "SMN deficiency does not induce oxidative stress in SMA iPSC-derived astrocytes or motor neurons" @default.
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• W2326678049 doi "https://doi.org/10.1093/hmg/ddv489" @default.
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