Neonatal exposure to intermittent hypoxia enhances mice performance in water maze and 8-arm radial maze tasks.
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.
Zhang
Jia-Xing
JX
Division of Neurobiology and Physiology, College of Life Sciences, Yuquan Campus,Zhejiang University, Hangzhou, 310027, China.
Chen
Xue-Qun
XQ
Du
Ji-Zeng
JZ
Chen
Qing-Mei
QM
Zhu
Chao-Yang
CY
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005106:Exploratory Behavior / Q000502:physiology; D006403:Hematologic Tests / Q000379:methods; D006624:Hippocampus / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D000860:Hypoxia / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology / Q000528:radiation effects; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission / Q000379:methods; D013569:Synapses / Q000648:ultrastructure
D017362:Cyclic AMP Response Element-Binding Protein