Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature

Diane C. Lim, Daniel C. Brady, Rajath Soans, Emily Y. Kim, Laise Valverde, Brendan T. Keenan, Xiaofeng Guo, Woo Young Kim, Min Jeong Park, Raymond Galante, James A. Shackleford, Allan I. Pack

Research output: Contribution to journalArticle

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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 O2 saturation (SaO2) 97%], severe CIH to inspired O2 fraction (FIO2) 0.10 (CIH10; SaO2 nadir of 61%), or very severe CIH to FIO2 0.05 (CIH5; SaO2 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 (PANOVA 0.065, PTREND 0.040), VEGFR2 (PANOVA 0.032, PTREND 0.429), and TIE-2 (PANOVA0.006, PTREND0.010). 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 (PANOVA0.042, PTREND0.012). Thus CIH affects the microvasculature in the hippocampus, but consequences depend on CIH severity.

Original languageEnglish (US)
Pages (from-to)78-88
Number of pages11
JournalJournal of Applied Physiology
Volume121
Issue number1
DOIs
StatePublished - Jul 1 2016

Fingerprint

Microvessels
Glucose Transporter Type 1
Hippocampus
Obstructive Sleep Apnea
Hypoxia
Messenger RNA
Inbred C57BL Mouse
Endothelial Cells
Immunohistochemistry
Air
Polymerase Chain Reaction

Keywords

  • Angiogenesis
  • Blood-brain barrier
  • Cyclical intermittent hypoxia
  • GLUT1 transporter
  • Obstructive sleep apnea
  • Vascular endothelium
  • VEGF

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Lim, D. C., Brady, D. C., Soans, R., Kim, E. Y., Valverde, L., Keenan, B. T., ... Pack, A. I. (2016). Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature. Journal of Applied Physiology, 121(1), 78-88. https://doi.org/10.1152/japplphysiol.01040.2015

Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature. / Lim, Diane C.; Brady, Daniel C.; Soans, Rajath; Kim, Emily Y.; Valverde, Laise; Keenan, Brendan T.; Guo, Xiaofeng; Kim, Woo Young; Park, Min Jeong; Galante, Raymond; Shackleford, James A.; Pack, Allan I.

In: Journal of Applied Physiology, Vol. 121, No. 1, 01.07.2016, p. 78-88.

Research output: Contribution to journalArticle

Lim, DC, Brady, DC, Soans, R, Kim, EY, Valverde, L, Keenan, BT, Guo, X, Kim, WY, Park, MJ, Galante, R, Shackleford, JA & Pack, AI 2016, 'Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature', Journal of Applied Physiology, vol. 121, no. 1, pp. 78-88. https://doi.org/10.1152/japplphysiol.01040.2015
Lim, Diane C. ; Brady, Daniel C. ; Soans, Rajath ; Kim, Emily Y. ; Valverde, Laise ; Keenan, Brendan T. ; Guo, Xiaofeng ; Kim, Woo Young ; Park, Min Jeong ; Galante, Raymond ; Shackleford, James A. ; Pack, Allan I. / Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature. In: Journal of Applied Physiology. 2016 ; Vol. 121, No. 1. pp. 78-88.
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