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Intermittent Hypoxia (IH) Impairs Hippocampal Oxygen Consumption and Neurophysiological Responses to Metabolic Challenge
Author(s) -
Polo Ashleigh K.,
Browe Brigitte,
Piao Lin,
Sharp Willard W.,
Garcia Alfredo J.
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r5978
Subject(s) - hippocampal formation , intermittent hypoxia , neuroscience , hippocampus , excitatory postsynaptic potential , endocrinology , hypoxia (environmental) , medicine , glycolysis , chemistry , biology , metabolism , obstructive sleep apnea , inhibitory postsynaptic potential , oxygen , organic chemistry
IH is a consequence of several clinical conditions such as sleep apnea. Previous work has shown that IH impairs many neurophysiological functions such as hippocampal adult neurogenesis and NMDAr‐dependent synaptic plasticity. While IH produces hippocampal oxidative stress, IH‐dependent changes in hippocampal metabolism may also contribute to impaired neurophysiology. The objective of this study is to understand how IH impacts hippocampal physiology in response to metabolic challenge. We hypothesize that ten days of IH perturbs hippocampal synaptic transmission when metabolically challenged. In vitro recordings of field excitatory post‐synaptic potentials (fEPSPs) from hippocampal slices showed that glucose deprivation (i.e., 30mM Fructose aCSF with 95% O 2 ) caused a complete loss of the fEPSP within 20min; whereas, the fEPSP in control tissue was reduced to 40% of baseline within the same period of time. This difference coincided with a reduction in both maximal and ATP‐linked O 2 consumption rates (OCRs) in hippocampal tissue following IH. Despite the reductions in hippocampal OCRs, neither ATP/ADP ratio nor lactate concentrations were different between the two groups. These data indicate that while ATP/ADP levels following IH are sufficiently maintained under basal conditions, metabolic processes fail to support synaptic physiology during glucose deprivation. Our ongoing experiments will further delineate how IH impacts the contribution of glycolytic and oxidative metabolism in the hippocampus. These findings may better define how IH impacts hippocampal responses to metabolic stressors, which could contribute to impairing hippocampal physiology in conditions such as sleep apnea.