Impaired Spatial Learning and Hyperactivity in Developing Rats Exposed to Intermittent Hypoxia

Abstract

Obstructive sleep apnea (OSA) is a frequent medical condition and is associated with cognitive impairments in adults and with hyperactivity and decreased school performance in children. In an adult rodent model, intermittent hypoxia (IH), such as occurs in OSA, is associated with neurodegenerative changes in the hippocampus and cortex and with spatial learning deficits. Because a unique developmental window of neural vulnerability to IH is present, we hypothesized that exposure to IH throughout the vulnerable ages would result in increased behavioral impairments in the juvenile rat. Rat pups were therefore exposed to either room air or IH beginning at postnatal (PN) d 10 until PN d 30. Learning and memory were assessed via a standard place-training version of the Morris water maze beginning at PN d 25. Locomotor activity was assessed on PN d 29 and 30. Pups exposed to IH displayed significant spatial learning impairments, and exposed male rats but not female rats displayed increased locomotor activity in the open field. Collectively, these findings indicate that exposure to IH at an age that corresponds to the peak incidence of OSA in children induces substantial learning impairment and gender-dependent behavioral hyperactivity in the juvenile rat. We postulate that this novel experimental model may allow for future exploration of mechanisms underlying the neurobehavioral deficits of children with OSA.

The UPR and the Anti-oxidant Response: Relevance to Sleep and Sleep Loss

“…Neurological deficits have also been associated with chronic intermittent hypoxia such as that encountered in OSA. Row et al reported an association between intermittent hypoxia, elevated lipid peroxidation, and oxidative stress in rat brain tissue [93]. This same study also demonstrated that impairments in spatial learning induced by redox alterations were attenuated by antioxidant treatment.…”

Neurobehavioral effects of obstructive sleep apnea: an overview and heuristic model

“…In one community survey, boys under age 8 showed an association between parent-reported snoring and hyperactivity, but older children and girls under 8 showed no such association [76]. Although this finding requires replication, it parallels analogous behavioral changes observed in male rat pups, but not female pups, after exposure to intermittent hypoxia [77].…”

Effects of Intermittent Hypoxia on Cognitive Performance and Quality of Life in Elderly Adults: A Pilot Study

“…However, this study aimed to elaborate on up to what extent IH further improves the positive effects of physical training on cognitive performance and QoL. On the one hand, severe levels of IH are associated with neurocognitive morbidity [42,43]. On the other hand, mild hypoxic training is not only innocuous [44], but mild hypoxic preconditioning also has a protective effect on neural viability of vulnerable hippocampal cells [45].…”