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It is well known that obstructive sleep apnea and associated intermittent hypoxemia cause deficit in learning and memory in human.We had shown previously that intermittent hypoxia (IH) impairs long-term potentiation (LTP) in hippocampal CA1 region of mice undergoing 7 d and 14 d of IH treatment.In this study we examined the effect of IH on the expression of brain-derived neurotrophic factor (BDNF),which is known to play a critical role in LTP.Four groups of adult male mice were exposed to 3 d IH,7 d IH,14-day IH and nomoxia environment respectively.The paradigm of IH consists of cycles of oxygen levels between 10% and 21% every 90 s (40 cycles/h) during the light phase for 8 h.The levels of the free mature neurotrophic factors BDNF,and also those of NT-3,NT-4/5 and nerve growth factor (NGF) in the hippocampi were determined by enzyme linked immunosorbent assay (ELISA).Significant decrease in free mature BDNF expression was found in both 7 d IH group (7 mice,77.8±23.0%,P < 0.05) and 14 d group (8 mice,43.9± 12.1%,P < 0.001),compared with the control group,while there was no significant change in the 3-day group (8 mice,94.4±21.6%,P > 0.05).Similar trends were observed in the case of NT-3 and NGF while there was no significant change in the level of NT-4/5.It is known that IH decreased the expression of phosphorylated cAMP response element binding protein (CREB).Our results support the notion that CREB-dependent transcription of genes,including BDNF,is impaired in IH,and which may underlie the impaired LTP in intermittent hypoxia.