Respiratory Responses Following H₂O₂Injections Into the Nucleus Tractus Solitarii (nTS) of an Alzheimer’s Disease (AD) Animal Model and Their Controls

AD is primarily known for memory loss, but the majority of patients also display respiratory dysfunction. Mechanisms may involve oxidative damage in brain areas important for respiratory control. The nTS of the brainstem is integral for respiration and affected in AD. Previously, we identified respiratory dysfunction and oxidative damage in the nTS of the streptozotocin (STZ)-induced AD animal model, leading to our current question about the interplay between these findings in STZ-AD. We induced AD by injecting 6-week-old Sprague-Dawley rats with 2.5 mg/kg of STZ into the fourth ventricle (5 µL/side). Control (CTL) rats received vehicle alone. Two weeks later, we implanted EMG electrodes into the diaphragm to assess respiratory responses to repeated nanoinjections of glutamate (20 nL, 40 mM) into the caudal nTS. We then compared respiratory responses to nTS glutamate with and without a single bolus of H 2 O 2 (40 nL, 37.5 mM) injected into that same location. Initial nTS glutamate increased respiratory frequency by 12-15 breaths/min (‘baseline response’), which was similar in CTL and STZ-AD animals. Then, we tested responses to glutamate following a single bout of H 2 O 2 or artificial CSF (aCSF, time-control). H 2 O 2 and aCSF injections by themselves did not change respiration. However, following aCSF, CTL animals had an elevated peak response to nTS glutamate when compared to the baseline response before aCSF treatment. This elevation of peak respiratory frequency was absent in the CTL group that received H 2 O 2 . In contrast, respiratory responses to glutamate in STZ-AD animals did not change from their baseline response following aCSF or H 2 O 2 . Next, we analyzed respiratory frequency responses under stress conditions with repeated glutamate exposure (10 injections, 5 min. apart). Typically, respiratory responses of all experimental groups accommodated by ~40-60% throughout the 10 glutamate injections. However, due to the elevation of glutamate responses in CTL after aCSF, all CTL responses to glutamate stress remained higher than those of STZ-AD. Following H 2 O 2 , response magnitudes of CTL were reduced to a level similar to STZ-AD. The elevated respiratory response of CTL rats in our time control condition (aCSF) may resemble a form of long-term facilitation with repeated and spaced glutamate injections. Inducing an oxidative environment (H 2 O 2 ) eliminated or prevented the elevation of response magnitude. Under such oxidative stress condition, responses of CTL animals also resembled those of STZ-AD. The absent change to H 2 O 2 in our STZ-AD group may be due to an already established oxidative environment from disease progression. Together, a better understanding of the changes in the respiratory system under oxidative stress from STZ-AD may help explain mechanisms involved with respiratory dysfunction in AD patients. NIH R15AG065927 (TDO & DO), KCOM Biomedical Graduate Program (GJF & TDO) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.