Journal article
Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature
Journal of applied physiology (1985), v 121(1)
01 Jul 2016
PMID: 27125850
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Abstract
Recent studies have shown an association between obstructive sleep apnea (OSA) and cognitive impairment. This study was done to investigate whether varied levels of cyclical intermittent hypoxia (CIH) differentially affect the microvasculature in the hippocampus, operating as a mechanistic link between OSA and cognitive impairment. We exposed C57BL/6 mice to sham [continuous air, arterial O-2 saturation (SaO(2)) 97%], severe CIH to inspired O-2 fraction (FIO2) = 0.10 (CIH10; SaO(2) nadir of 61%), or very severe CIH to FIO2 = 0.05 (CIH5; SaO(2) nadir of 37%) for 12 h/day for 2 wk. We quantified capillary length using neurostereology techniques in the dorsal hippocampus and utilized quantitative PCR methods to measure changes in sets of genes related to angiogenesis and to metabolism. Next, we employed immunohistochemistry semiquantification algorithms to quantitate GLUT1 protein on endothelial cells within hippocampal capillaries. Capillary length differed among CIH severity groups (P = 0.013) and demonstrated a linear relationship with CIH severity (P = 0.002). There was a strong association between CIH severity and changes in mRNA for VEGFA (P < 0.0001). Less strong, but nominally significant associations with CIH severity were also observed for ANGPT2 (P-ANOVA = 0.065, P-TREND = 0.040), VEGFR2 (P-ANOVA = 0.032, P-TREND = 0.429), and TIE-2 (P-ANOVA = 0.006, P-TREND = 0.010). We found that the CIH5 group had increased GLUT1 protein relative to sham (P = 0.006) and CIH10 (P = 0.001). There was variation in GLUT1 protein along the microvasculature in different hippocampal subregions. An effect of CIH5 on GLUT1 mRNA was seen (P-ANOVA = 0.042, P-TREND = 0.012). Thus CIH affects the microvasculature in the hippocampus, but consequences depend on CIH severity.
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Details
- Title
- Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature
- Creators
- Diane C. Lim - University of PennsylvaniaDaniel C. Brady - University of PennsylvaniaRajath Soans - Drexel UniversityEmily Y. Kim - University of PennsylvaniaLaise Valverde - Superior School of Health Sciences, Brasilia, Brazil; and.Brendan T. Keenan - University of PennsylvaniaXiaofeng Guo - University of PennsylvaniaWoo Young Kim - Korea University, Seoul, KoreaMin Jeong Park - Korea University, Seoul, KoreaRaymond Galante - University of PennsylvaniaJames A. Shackleford - Drexel UniversityAllan I. Pack - University of Pennsylvania
- Publication Details
- Journal of applied physiology (1985), v 121(1)
- Publisher
- Amer Physiological Soc
- Number of pages
- 11
- Grant note
- Han Eol Program K12HL090021 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) ASMF 56-PA-10 / American Sleep Medicine Foundation [Physician Scientist Training Award] HL-094307 / NHLBI Grant Science Without Borders Program-Coordination for the Improvement of Higher Education Personnel, Ministry of Education, Brazil T32-HL-07713; K12-HL-090021 / National Heart, Lung, and Blood Institute (NHLBI); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Electrical and Computer Engineering
- Web of Science ID
- WOS:000380750700010
- Scopus ID
- 2-s2.0-84983747556
- Other Identifier
- 991019168374804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Physiology
- Sport Sciences