Physical Activity Attenuates Intermittent Hypoxia-induced Spatial Learning Deficits and Oxidative Stress

Abstract

Rationale: Exposure to intermittent hypoxia (IH), such as occurs in sleep-disordered breathing, is associated with substantial cognitive impairments, oxidative stress and inflammation, and increased neuronal cell losses in brain regions underlying learning and memory in rats. Physical activity (PA) is now recognized as neuroprotective in models of neuronal injury and degeneration. Objectives: To examine whether PA will ameliorate IH-induced deficits. Methods: Young adult Sprague-Dawley rats were randomly assigned to one of four treatment groups including normal activity (NA) or PA for 3 months and then subjected to either normoxia (RA) or exposure to IH during the light phase during the last 14 days. Measurements and Main Results: Significant impairments in IHexposed rats emerged on both latency and pathlength to locate the hidden platform in a water maze and decreased spatial bias during the probe trials. These impairments were not observed in PA-IH rats. In addition, the PA-IH group, relative to NA-IH, conferred greater resistance to both lipid peroxidation and 8-hydroxy-29-deoxyguanosine (DNA damage) in both the cortex and hippocampus. In support of a neuroprotective effect from PA, PA-IH versus NA-IH rats showed greater AKT activation and neuronal insulin growth factor-1 in these regions. Conclusions: Behavioral modifications such as increased physical activity are associated with decreased susceptibility to IH-induced spatial task deficits and lead to reduced oxidative stress, possibly through improved preservation of insulin growth factor-1-Akt neuronal signaling. Considering the many advantages of PA, interventional strategies targeting behavioral modifications leading to increased PA should be pursued in patients with sleep-disordered breathing.

Sleep Fragmentation Induces Cognitive Deficits Via Nicotinamide Adenine Dinucleotide Phosphate Oxidase–dependent Pathways in Mouse

“…The present study demonstrates that 12 hours of SF during the daylight period for 14 days, which aims to mimic sleep apnea, interferes with spatial learning and retention memory tests in a well-defined hippocampus-dependent learning and memory task (14,42). The SF-induced performance deficits in the water maze could be mediated by a disturbance in hippocampaldependent memory consolidation.…”

Growth hormone releasing hormone (GHRH) signaling modulates intermittent hypoxia‐induced oxidative stress and cognitive deficits in mouse

“…Development of rodent models mimicking components of OSA have yielded important insights into the mechanistic pathways underlying neural injury in the context of IH and SF, and have particularly pointed out the critical role of oxidative stress and inflammation-mediated neural injury in this context (Nair et al 2011b, Nair et al 2011a). Earlier studies from our laboratory indicated that exogenous growth hormone (GH) administration was anti-apoptotic and neuroprotective in the context of IH-induced neuronal injury, and that physical activity-associated neuroprotective effects during IH were mediated, at least in part, by endogenous increases in neuronal expression of IGF-1 (Li et al 2011, Gozal et al 2001, Gozal et al 2010). However, the possibility that growth hormone-releasing hormone (GHRH) may also be neuroprotective was not explored.…”

Exogenous growth hormone attenuates cognitive deficits induced by intermittent hypoxia in rats

“…Indeed, the expression of these 4 genes is tightly regulated in the CNS by HIF-1α (Freeman and Barone, 2005;Acker and Acker, 2004), and plays a major protective role in hypoxia and ischemia-induced brain injury (Sharp et al, 2004;Fan et al, 2009). SDB is associated with suppression of growth hormone (GH) secretion (Meston et al, 2003;Cooper et al, 1995;Saini et al, 1993), the presence or absence of cognitive deficits is dependent on the serum levels of IGF-1 at any given level of severity of SDB, and in rodents, physical activity that stimulates IGF-1 is neuroprotective, suggesting that GH suppression may play a role in SDB-associated neurocognitive deficits (Gozal et al, 2009;Gozal et al, 2010). Based on these considerations, the aims of present study were to determine whether similar to IH, CH is associated with spatial learning and memory deficits, and whether exogenous systemic administration of GH will protect the brain from IH-induced neuronal apoptosis and consequent functional deficits.…”