The development but not the maintenance of phrenic and sympathetic long-term facilitation after acute intermittent hypoxia requires nucleus tractus solitarii H2O2
Document Type
Article
Publication Title
Experimental Neurology
Abstract
Acute exposure to intermittent hypoxia (AIH) produces prolonged increases (long-term facilitation, LTF) in phrenic (PhrNA) and sympathetic (SNA) nerve activity (pLTF and sLTF, respectively) during non-hypoxic periods, and augments cardiorespiratory responses to hypoxia. We recently showed that neuronal activity in the nucleus tractus solitarii (nTS) is required for the induction and maintenance of LTF. However, the specific mechanisms involved were not determined. Because bouts of deoxygenation/reoxygenation produce reactive oxygen species and H2O2 contributes to plasticity in the nTS, we hypothesized that nTS H2O2 contributes to AIH-induced LTF and augmented hypoxic responses. We reduced H2O2 within the nTS acutely by nanoinjecting catalase or chronically by overexpressing catalase via an adenovirus vector. We then evaluated PhrNA and splanchnic SNA (SSNA) in animals subjected to AIH or time control. In control rats subjected to nTS nanoinjections of aCSF or overexpression of eGFP, AIH produced pLTF and sLTF, and augmented PhrNA responses to hypoxia. Reducing nTS H2O2 by either nTS nanoinjections or overexpression of catalase markedly attenuated the development of pLTF and sLTF. Augmented hypoxic responses due to AIH also were diminished. In contrast, after LTF had developed, nanoinjection of catalase had no effect on the magnitude of either PhrNA or SSNA although inhibiting nTS neuronal activity after LTF development reduced pLTF. The data indicate that nTS H2O2 is required for AIH-induced pLTF and sLTF, as well as augmentation of responses to hypoxia. Moreover, while nTS neuronal activity is essential to the maintenance of pLTF once developed, ongoing increases in H2O2 are not required.
DOI
10.1016/j.expneurol.2025.115380
Publication Date
11-1-2025
Recommended Citation
Ostrowski, Daniela; Heesch, Cheryl M.; Hollenbeck, Allison C.; and Graber, Alexis B., "The development but not the maintenance of phrenic and sympathetic long-term facilitation after acute intermittent hypoxia requires nucleus tractus solitarii H2O2" (2025). KCOM Student Publications. 69.
https://scholarworks.atsu.edu/kcom-student/69