Chronic intermittent hypoxia increases encoding pigment epithelium-derived factor gene expression, although not that of the protein itself, in the temporal cortex of rats.
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.
Federal University of São Paulo, Paulista School of Medicine, Department of Psychobiology, São Paulo, Brazil. Department of Psychobiology, Federal University of São Paulo Paulista School of Medicine, São Paulo, Brazil.
Guilherme Silva
GS
Julian
Federal University of São Paulo, Paulista School of Medicine, Department of Psychobiology, São Paulo, Brazil. Department of Psychobiology, Federal University of São Paulo Paulista School of Medicine, São Paulo, Brazil.
Renato Watanabe de
RW
Oliveira
Federal University of São Paulo, Paulista School of Medicine, Department of Psychobiology, São Paulo, Brazil. Department of Psychobiology, Federal University of São Paulo Paulista School of Medicine, São Paulo, Brazil.
Vanessa Manchim
VM
Favaro
Federal University of São Paulo, Paulista School of Medicine, Department of Psychobiology, São Paulo, Brazil. Department of Psychobiology, Federal University of São Paulo Paulista School of Medicine, São Paulo, Brazil.
Maria Gabriela Menezes de
MG
Oliveira
Federal University of São Paulo, Paulista School of Medicine, Department of Psychobiology, São Paulo, Brazil. Department of Psychobiology, Federal University of São Paulo Paulista School of Medicine, São Paulo, Brazil.
Juliana Cini
JC
Perry
Federal University of São Paulo, Paulista School of Medicine, Department of Psychobiology, São Paulo, Brazil. Department of Psychobiology, Federal University of São Paulo Paulista School of Medicine, São Paulo, Brazil.
Sergio
S
Tufik
Federal University of São Paulo, Department of Biosciences, Santos, Brazil. Department of Psychobiology, Federal University of São Paulo Paulista School of Medicine, São Paulo; and Department of Biosciences, Federal University of São Paulo, Baixada Santista Campus, Santos, Brazil.
Jair Ribeiro
JR
Chagas
D000818:Animals; D003072:Cognition Disorders / Q000209:etiology; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics*; D015870:Gene Expression; D006624:Hippocampus / Q000473:pathology; D000860:Hypoxia / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008568:Memory; D008569:Memory Disorders / Q000209:etiology; D009414:Nerve Growth Factors / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D015843:Serpins / Q000235:genetics*; D020181:Sleep Apnea, Obstructive / Q000235:genetics* / Q000503:physiopathology; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor
Cognition; Disease models, animal; Sleep; Sleep apnea, central; Sleep apnea, obstructive