Physical activity attenuates intermittent hypoxia-induced spatial learning deficits and oxidative stress.
BACKGROUND
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.


OBJECTIVE
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.


RESULTS
Significant impairments in IH-exposed 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-2'-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.
Department of Pediatrics, Comer Children's Hospital, Pritzker School of Medicine, The University of Chicago, 5721 South Maryland Avenue, MC 8000, Suite K-160, Chicago, IL 60637, USA. dgozal@uchicago.edu
David
D
Gozal
Deepti
D
Nair
Aviv D
AD
Goldbart
D000818:Animals; D005081:Exercise Therapy; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications*; D008569:Memory Disorders / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D051057:Proto-Oncogene Proteins c-akt