Chronic intermittent hypoxia increases encoding pigment epithelium-derived factor gene expression, although not that of the protein itself, in the temporal cortex of rats,

Abstract

Objective: Obstructive sleep apnea syndrome is mainly characterized by intermittent hypoxia (IH) during sleep, being associated with several complications. Exposure to IH is the most widely used animal model of sleep apnea, short-term IH exposure resulting in cognitive and neuronal impairment. Pigment epithelium-derived factor (PEDF) is a hypoxia-sensitive factor acting as a neurotrophic, neuroprotective, and antiangiogenic agent. Our study analyzed performance on learning and cognitive tasks, as well as PEDF gene expression and PEDF protein expression in specific brain structures, in rats exposed to long-term IH. Methods: Male Wistar rats were exposed to IH (oxygen concentrations of 21-5%) for 6 weeks-the chronic IH (CIH) group-or normoxia for 6 weeks-the control group. After CIH exposure, a group of rats were allowed to recover under normoxic conditions for 2 weeks (the CIH+N group). All rats underwent the Morris water maze test for learning and memory, PEDF gene expression and PEDF protein expression in the hippocampus, frontal cortex, and temporal cortex being subsequently assessed. Results: The CIH and CIH+N groups showed increased PEDF gene expression in the temporal cortex, PEDF protein expression remaining unaltered. PEDF gene expression and PEDF protein expression remained unaltered in the frontal cortex and hippocampus. Long-term exposure to IH did not affect cognitive function. Conclusions: Long-term exposure to IH selectively increases PEDF gene expression at the transcriptional level, although only in the temporal cortex. This increase is probably a protective mechanism against IH-induced injury.

Sex-dependent effects of chronic intermittent hypoxia: Implication for obstructive sleep apnea

“…It should be noted that these prior studies in which CIH induced spatial learning and memory impairments and anxiety-like behaviors were conducted with different CIH protocols (AHI ranged from 40-60) [47,52,[54][55][56][57][58] compared to our CIH protocol (AHI = 10). Indeed, a study using a CIH protocol with an AHI of 20 found no effect of CIH on spatial learning and memory in male rats [110], and another study using an AHI of 15 found no effects on anxiety-like behavior in the open eld in male and female mice [59]. These ndings indicate that CIH protocols with > 20 AHI is necessary to induce spatial learning and memory impairments and anxiety-like behaviors.…”

Sex-dependent effects of chronic intermittent hypoxia: implication for obstructive sleep apnea

“…It should be noted that these prior studies in which CIH induced spatial learning and memory impairments and anxiety-like behaviors were conducted with different CIH protocols (AHI ranged from 40 to 60) [ 53 , 58 , 60 – 64 ] compared to our CIH protocol (AHI = 10). Indeed, a study using a CIH protocol with an AHI of 20 found no effect of CIH on spatial learning and memory in male rats [ 133 ], and another study using an AHI of 15 found no effects on anxiety-like behavior in the open field in male and female mice [ 66 ]. These findings indicate that CIH protocols with > 20 AHI is necessary to induce spatial learning and memory impairments and anxiety-like behaviors.…”

Intermittent hypoxia induces mandibular growth arrest and invokes a different response in condylar and tibial cartilage in infant rats

“…As discussed in previous animal studies, postnatal hyperoxic/hypoxemic exposure diminished peripheral chemoreceptors functions, and hypoxic ventilatory responses. Such an effects in early life contribute to lifelong alteration in respiratory control (53)(54)(55)(56).…”