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Repetitive acute intermittent hypoxia downregulates inflammatory gene expression in the rat ventral cervical spinal cord (1091.7)
Author(s) -
Watters Jyoti,
Roopra Avtar,
Bowen Kellie,
Vinit Stephane,
Macfarlane Peter,
Mitchell Gordon
Publication year - 2014
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.28.1_supplement.1091.7
Subject(s) - intermittent hypoxia , hypoxia (environmental) , biology , neuroinflammation , spinal cord , transcription factor , gene expression , gene , inflammation , endocrinology , medicine , immunology , neuroscience , chemistry , genetics , obstructive sleep apnea , organic chemistry , oxygen
Intermittent hypoxia exerts pathologic and beneficial effects in the CNS, depending on the dose and duration. Whereas hundreds of hypoxic episodes per day mimic sleep apnea and promote neuroinflammation, “low dose” protocols, such as repetitive acute intermittent hypoxia (rAIH; 10 episodes of 10.5% O 2 per day, 3 days/week for 4 weeks), upregulate growth/trophic factors and promote spinal motor plasticity. Because rAIH increases protein levels of key molecules associated with spinal respiratory motor plasticity, we hypothesized that the mRNAs for these and other molecules contributing to neuronal plasticity would be similarly increased. Nimblegen neuronal gene microarrays were used to profile transcript levels in the spinal ventral horn (C4‐C6) of male Lewis rats exposed to normoxia or rAIH (n=3 arrays/condition). Surprisingly, there was little evidence of increased mRNA levels of pro‐plasticity genes, and these results were confirmed with qRT‐PCR for specific genes of interest. Instead, there were significant decreases in inflammatory genes including cyclooxygenase‐2, tumor necrosis factor family members, chemokines and interleukins 1β and 6. To explore the cause of these changes, we used whole genome Vista analyses to identify the transcription factor binding sites over‐represented in the upstream 5kb promoter regions of genes affected by rAIH. Genes with binding sites for nuclear factor kappa B (NF‐kB) were the most over‐represented (p<0.005), suggesting that rAIH may decrease NF‐kB transcriptional activity. Thus, in contrast to chronic intermittent hypoxia, rAIH may be anti‐inflammatory, depleting spinal NF‐kB target genes. Grant Funding Source : Supported by NIH HL111598, HL080209, HL69064 and NS065067