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A Role for Hypoxia‐inducible Factor 1‐alpha (HIF1a) Signaling in Suppressing Synaptic Plasticity and Spatial Memory During Intermittent Hypoxia
Author(s) -
Nwakudu Chinwendu U.,
Barnard Jasmine,
Khuu Maggie A.,
Garcia Alfredo J.
Publication year - 2018
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.2018.32.1_supplement.727.8
Subject(s) - long term potentiation , hif1a , synaptic plasticity , hypoxia (environmental) , hippocampal formation , neuroscience , excitatory postsynaptic potential , neuroplasticity , schaffer collateral , medicine , sleep apnea , hippocampus , endocrinology , biology , chemistry , inhibitory postsynaptic potential , angiogenesis , receptor , organic chemistry , oxygen
Although HIF1a signaling is commonly identified as a mediator of positive homeostatic responses to hypoxia, during intermittent hypoxia (IH), a primary effect of sleep apnea, HIF1a signaling can cause oxidative stress in the body. IH‐dependent oxidative stress can lead to pathophysiological changes throughout the nervous system associated with sleep apnea. The objective of this study is to determine whether HIF1a signaling during IH opposes or facilitates IH‐dependent suppression in synaptic plasticity and spatial memory. Both adult wildtype mice (WT) and mice heterozygous for HIF1a (HIF1a +/− ) were either unexposed (control) or exposed to chronic intermittent hypoxia (CIH) for 10 days. Hippocampal brain slices (350 microns thick) were prepared from mice of each group. Extracellular recordings of the field excitatory postsynaptic potential (fEPSP) were made before and after the induction of long‐term potentiation (LTP) in area CA1. While LTP occurred in brain slices of WT from both groups, the magnitude of LTP was larger in the control group (164±6% of baseline, n=5) as compared to the CIH group (115±10% of baseline, n=5). LTP in the brain slices from the HIF1a +/− exposed to CIH was 152±10% of baseline (n=5), which was greater in magnitude compared to WT LTP in the CIH group. Ongoing experiments suggest spatial memory in the Barnes Maze is unaffected by CIH in HIF1a +/− . These findings show that IH‐dependent HIF1a signaling disrupts hippocampal synaptic plasticity and spatial memory, which may contribute to cognitive impairment associated with sleep apnea. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .