Platelet-activating factor receptor-deficient mice are protected from experimental sleep apnea-induced learning deficits.
Intermittent hypoxia (IH) during sleep, a hallmark of sleep apnea, is associated with neurobehavioral impairments, regional neurodegeneration and increased oxidative stress and inflammation in rodents. Platelet-activating factor (PAF) is an important mediator of both normal neural plasticity and brain injury. We report that mice deficient in the cell surface receptor for PAF (PAFR-/-), a bioactive mediator of oxidative stress and inflammation, are protected from the spatial reference learning deficits associated with IH. Furthermore, PAFR-/- exhibit attenuated elevations in inflammatory signaling (cyclo-oxygenase-2 and inducible nitric oxide synthase activities), degradation of the ubiquitin-proteasome pathway and apoptosis observed in wild-type littermates (PAFR+/+) exposed to IH. Collectively, these findings indicate that inflammatory signaling and neurobehavioral impairments induced by IH are mediated through PAF receptors.
Row
Barry W
BW
Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, Kentucky 40202, USA.
Kheirandish
Leila
L
Li
Richard C
RC
Guo
Shang Z
SZ
Brittian
Kenneth R
KR
Hardy
Mattie
M
Bazan
Nicolas G
NG
Gozal
David
D
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001273:Atmosphere Exposure Chambers / Q000009:adverse effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2; D003546:Cysteine Endopeptidases / Q000378:metabolism; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism; D007859:Learning Disabilities / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics*; D012891:Sleep Apnea Syndromes / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D013037:Spatial Behavior / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism
D007527:Isoenzymes; D009097:Multienzyme Complexes; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D025801:Ubiquitin; C039351:platelet activating factor receptor; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex