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Prolonged intermittent hypoxia activates p38 MAP kinase in the phrenic motor nucleus
Author(s) -
Peterson Timothy J,
Huxtable Adrianne G,
Mitchell Gordon S
Publication year - 2013
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.27.1_supplement.721.2
Subject(s) - intermittent hypoxia , hypoxia (environmental) , phrenic nerve , inflammation , p38 mitogen activated protein kinases , microglia , respiratory system , medicine , neuroscience , mapk/erk pathway , biology , anesthesia , immunology , kinase , microbiology and biotechnology , chemistry , organic chemistry , oxygen , obstructive sleep apnea
Plasticity is a fundamental property of the neural system controlling breathing. Although inflammation is prominent during most clinical disorders that challenge ventilatory control, little is known concerning the influence of inflammation on respiratory plasticity. One trigger to systemic (and neural) inflammation is prolonged (one day) intermittent hypoxia (IH‐1; 2 min hypoxia/2 min normoxia, 8 hrs), simulating intermittent hypoxia during sleep disordered breathing. IH‐1 abolishes an important model of respiratory plasticity, phrenic long‐term facilitation, but this effect is reversed by spinal application of a p38 MAP kinase inhibitor. p38 MAPK both initiates and is activated by inflammation. Here, we sought to determine which cells in the phrenic motor nucleus express increased phosphorylated (activated) p38 MAPK following IH‐1. Using immunofluorescence (n=5), increased phospho‐p38 MAPK was detected in identified phrenic motoneurons (Cholera Toxin B labeled) and adjacent microglia (cd11b positive cells). These results suggest that p38 MAPK activity may impair pLTF following IH‐1 by: 1) disrupting pLTF within phrenic motor neurons; and/or 2) initiating microglial inflammatory cascades that indirectly impair pLTF. p38 MAPK may be a viable therapeutic target to reduce the impact of inflammation on respiratory plasticity. Supported by HL111598 , APS UGSRF Program