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

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.

Hypoxic Preconditioning Improves Spatial Cognitive Ability in Mice

“…Compared with the control group, the spatial cognitive ability of mice exposed to hypoxia once was not changed. Zhang et al [24,32] have reported that intermittent hypoxia could enhance spatial cognitive ability in young mice but did not affect this ability in adult mice. Others also reported that brief hypobaric hypoxia enhanced animals' cognition.…”

“…The ICR mice were developed from the Swiss-Webster albino mice and have been used as a model to explore the cognitive ability under hypoxia condition [24] . A total of 90 male adult ICR mice (16.0-22.0 g) were separated into 3 groups randomly and exposed, respectively, to hypoxia for 4 runs (group H4), 1 run (group H1) and 0 runs (group H0).…”

The Contribution of Intermittent Hypoxemia to Late Neurological Handicap in Mice with Hyperoxia-Induced Lung Injury

“…For example, chronic intermittent hypoxia in neonatal mice (exposure to 16% O 2 for 4 h/day ! 3 weeks) significantly improved longterm spatial learning and memory tested in water maze and radial arm paradigms [24] . In contrast, exposure of immature rats to 10% O 2 (6 h/day for 20 days) resulted in significant long-term alteration of spatial memory tested using water maze [11] .…”

Delivery of <em>In Vivo</em> Acute Intermittent Hypoxia in Neonatal Rodents to Prime Subventricular Zone-derived Neural Progenitor Cell Cultures

“…This group has significant experience with the administration of systemic IH, and has conducted extensive studies on the role of IH in respiratory plasticity [3][4][5][6][7] . This work, and the recent finding that chronic IH increased neurogenesis in the rodent CNS [8][9][10] , forms the basis for the exploration of acute in vivo hypoxia as a preconditioning stimulus (i.e., prior to tissue harvest) on the subsequent culture of neural stem/progenitor cells (NPCs) 11 . Remarkably, when mouse pups were exposed to a brief (<1 hr) period of acute intermittent hypoxia (AIH), cells that were harvested from the subventricular zone (SVZ) had significantly increased capacity for expansion as neurospheres or adherent monolayer cells.…”

“…In other published work, neonates were treated as a litter with the dam in hypobaric chambers, which allows for chronic dosing, less handling prior to treatment, and maintained maternal contact during treatment 9 . The current approach bypasses repeated treatments to a breeding female, or the use of a different dam for each experiment.…”