Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature
| Autor: | Brendan T. Keenan, Xiaofeng Guo, James Shackleford, Emily Y. Kim, Min Jeong Park, Allan I. Pack, Rajath E. Soans, Woo Young Kim, Raymond J. Galante, Diane C. Lim, Daniel C. Brady, Laise Valverde |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine medicine.medical_specialty Pathology Physiology Angiogenesis Hippocampal formation Blood–brain barrier Hippocampus Angiopoietin-2 Mice 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine medicine Animals RNA Messenger Hypoxia Glucose Transporter Type 1 Sleep Apnea Obstructive biology business.industry Intermittent hypoxia Articles Hypoxia (medical) medicine.disease Receptor TIE-2 Vascular Endothelial Growth Factor Receptor-2 Capillaries Mice Inbred C57BL Obstructive sleep apnea Disease Models Animal Vascular endothelial growth factor A 030104 developmental biology Endocrinology medicine.anatomical_structure nervous system Microvessels biology.protein GLUT1 medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Applied Physiology. 121:78-88 |
| ISSN: | 1522-1601 8750-7587 |
| DOI: | 10.1152/japplphysiol.01040.2015 |
| Popis: | 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 (PANOVA = 0.006, PTREND = 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 (PANOVA = 0.042, PTREND = 0.012). Thus CIH affects the microvasculature in the hippocampus, but consequences depend on CIH severity. |
| Databáze: | OpenAIRE |
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