Neonatal exposure to intermittent hypoxia enhances mice performance in water maze and 8-arm radial maze tasks

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Abstract
Hypoxia has generally been reported to impair learning and memory. Here we established a hypoxia‐enhanced model. Intermittent hypoxia (IH) was simulated at 2 km (16.0% O2) or 5 km (10.8% O2) in a hypobaric chamber for 4 h/day from birth to 1, 2, 3, or 4 week(s), respectively. Spatial learning and memory ability was tested in the Morris water maze (MWM) task at ages of postnatal day 36 (P36)–P40 and P85–89, respectively, and in the 8‐arm maze task at P60–68. The long‐term potentiation (LTP), synaptic density, and phosphorylated cAMP‐responsive element‐binding protein (p‐CREB) level in the hippocampus were measured in mice at P36 under the IH for 4 weeks (IH‐4w). The results showed that IH for 3 weeks (IH‐3w) and IH‐4w at 2 km significantly reduced the escape latencies of mice at P36–40 in the MWM task with significantly enhanced retention, and this spatial enhancement was further confirmed by the 8‐arm maze test in mice at P60–68. The improvement in MWM induced by IH‐4w at 2 km was still maintained in mice at P85–89. IH‐4w at 2 or 5 km significantly increased amplitude of LTP, the number of synapse, and the p‐CREB level in the hippocampus of P36 mice. These results indicated that IH (4 h/day) exposure to neonatal mice at 2 km for 3 or 4 weeks enhanced mice spatial learning and memory, which was related to the increased p‐CREB, LTP, and synapses of hippocampus in this model. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2005