The Effect Of Intermittent Hypoxia On Spatial Learning And Memory In Neonatal Mice

Stress can affect the animals' learning and memory behavior. Heavy stress will impair learning and memory, while moderate stress has an improvement effect. Glucocorticoids, such as corticosterone, are released by the adrenal cortex in response to a wide range of stressors and related with learning and memory. These notably bind to mineralcorticoid and glucocorticoid receptors (MRs and GRs) in the hippocampus, which is involved in the processing of spatial and contextual information. The effects of stress and glucocorticoids on hippocampus-dependent learning follow an inverted U-shaped dose-response relationship;extreme low and high levels may impair consolidation, whereas moderate activation seems to be a prerequisite for the long-term storage of information. SGK (serum and glucocorticoid regulated protein kinase) which is a kind of kinase stimulated by glucocorticoid can regulate many ionic channels and helpful to neurons survival and axon regeneration. Some researches narrated that SGK high expression can improve special learning and memory. The present study is designed to detect how intermittent hypoxia (IH) affects mice learning and memory when mice were exposed to IH. Mice were exposed to a simulated hypobaric hypoxia, by the way of 4h/day, and set at around altitude of 2 km (16.0% O₂;PaO₂, 60mmHg) or 5 km (10.8% O₂;PaO₂,41mmHg). Spatial learning and memory ability was tested in the Morris water maze (MWM). Glucorcorticoid and GR and SGK were detected.Results1, Compared with controls (set at sea level, 21% O₂), postnatal IH-3w and IH-4w at 2 km and 5 km significantly reduced the length to the platform of male mice at postnatal day (P) 36 (P36) -P39 in MWM task, while in female groups, IH 2w and 4w at 2km increase the length to the platform. There is no change in the retention test at P40 of male and female mouse.2, After IH for 4 weeks, the GR/GRmRNA expression significantly intense-dependently increased in P28 mice's hippocampus, while did not in P35 mice. The SGK/ SGKmRNA expression was significantly upregulated in both P28and P35 mice.3^ IH have a negative effect on the neonatal mice body weight increasing. But this negative effect disappeared few days after IH.Conclusion1> Neonatal exposure to intermittent hypoxia enhanced or depressed mice spatiallearning and memory, which are related to IH exposure time. 2> IH can increase GR and SGK expression in hippocampus and stimulate HPA axis,suggesting that SGK and GR may relate to learning and memory behavior. 3n Body weight was inhibited by IH, but it was not related to the spatial learning andmemory.