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Neilsen Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100005191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:p>Moderate acute intermittent hypoxia (mAIH) elicits a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Preconditioning with modest protocols of chronic intermittent hypoxia enhances pLTF, demonstrating pLTF metaplasticity. Since \u201clow-dose\u201d protocols of repetitive acute intermittent hypoxia (rAIH) show promise as a therapeutic modality to restore respiratory (and nonrespiratory) motor function in clinical disorders with compromised breathing, we tested 1) whether preconditioning with a mild rAIH protocol enhances pLTF and hypoglossal (XII) LTF and 2) whether the enhancement is regulated by glycolytic flux. In anesthetized, paralyzed, and ventilated adult male Lewis rats, mAIH (three 5-min episodes of 10% O<jats:sub>2<\/jats:sub>) elicited pLTF (pLTF at 60 min post-mAIH: 49\u2009\u00b1\u20095% baseline). rAIH preconditioning (ten 5-min episodes of 11% O<jats:sub>2<\/jats:sub>\/day with 5-min normoxic intervals, 3 times per week, for 4 wk) significantly enhanced pLTF (100\u2009\u00b1\u200916% baseline). XII LTF was unaffected by rAIH. When glycolytic flux was inhibited by 2-deoxy-d-glucose (2-DG) administered via drinking water (~80 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>), pLTF returned to normal levels (58\u2009\u00b1\u20098% baseline); 2-DG had no effect on pLTF in normoxia-pretreated rats (59\u2009\u00b1\u20097% baseline). In ventral cervical (C<jats:sub>4\/5<\/jats:sub>) spinal homogenates, rAIH increased inducible nitric oxide synthase mRNA vs. normoxic controls, an effect blocked by 2-DG. However, there were no detectable effects of rAIH or 2-DG on several molecules associated with phrenic motor plasticity, including serotonin 2A, serotonin 7, brain-derived neurotrophic factor, tropomyosin receptor kinase B, or VEGF mRNA. We conclude that modest, but prolonged, rAIH elicits pLTF metaplasticity and that a drug known to inhibit glycolytic flux (2-DG) blocks pLTF enhancement.<\/jats:p>","DOI":"10.1152\/ajpregu.00306.2017","type":"journal-article","created":{"date-parts":[[2017,10,12]],"date-time":"2017-10-12T00:40:24Z","timestamp":1507768824000},"page":"R135-R144","source":"Crossref","is-referenced-by-count":16,"title":["Enhancement of phrenic long-term facilitation following repetitive acute intermittent hypoxia is blocked by the glycolytic inhibitor 2-deoxyglucose"],"prefix":"10.1152","volume":"314","author":[{"given":"P. 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