Abstract
Acute intermittent hypoxia (AIH; 3, 5‐min episodes, 11% O2) elicits a form of respiratory plasticity known as pLTF. In normal rats, pLTF requires NADPH oxidase activity and superoxide formation. Since enhanced pLTF is observed in SOD1G93A rats at disease end‐stage (Nichols et al., 2011) despite increased superoxide dismutase‐1 expression and decreased superoxide accumulation in phrenic motor neurons (Satriotomo et al., 2008), we tested the hypothesis that AIH‐induced pLTF is NADPH oxidase independent in anesthetized,paralyzed and ventilated end‐stage SOD1G93A rats (versus age‐matched, wild‐type littermates). Following intrathecal injections of vehicle (control) or an NADPH oxidase inhibitor (apocynin; 600μM; 12μL), pLTF was abolished in wild‐type (7±3%, n = 4; controls: 40±4%, n=5; p<0.05), but not end‐stage SOD1G93A rats (78±15%, n = 4; controls: 92±18%, n=4; p>0.05). Since pLTF is no longer dependent on NADPH oxidase activity in end‐stage SOD1G93A rats, we suggest that key molecular targets of reactive oxygen species that normally constrain pLTF (e.g. protein phosphatases) are down‐regulated with disease progression in ALS.[Supported by NIH K99 HL119606, R01 HL080209 and R01 HL069064]
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