title: Global hypoxia induced impairment in learning and spatial memory is associated with precocious hippocampal aging.
abstract: Both chronological aging and chronic hypoxia stress have been reported to cause degeneration of hippocampal CA3 neurons and spatial memory impairment through independent pathways. However, the possible occurrence of precocious biological aging on exposure to single episode of global hypoxia resulting in impairment of learning and memory remains to be established. The present study thus aimed at bridging this gap in existing literature on hypoxia induced biological aging. Male Sprague Dawley rats were exposed to simulated hypobaric hypoxia (25,000ft) for different durations and were compared with aged rats. Behavioral studies in Morris Water Maze showed decline in learning abilities of both chronologically aged as well as hypoxic rats as evident from increased latency and pathlength to reach target platform. These behavioral changes in rats exposed to global hypoxia were associated with deposition of lipofuscin and ultrastructural changes in the mitochondria of hippocampal neurons that serve as hallmarks of aging. A single episode of chronic hypobaric hypoxia exposure also resulted in the up-regulation of pro-aging protein, S100A9 and down regulation of Tau, SNAP25, APOE and Sod2 in the hippocampus similar to that in aged rats indicating hypoxia induced accelerated aging. The present study therefore provides evidence for role of biological aging of hippocampal neurons in hypoxia induced impairment of learning and memory.
authors.affiliation: Defence Institute of High Altitude Research, C/o 56 APO, Leh-Ladakh, Jammu & Kashmir 901205, India.
authors.forename: Suryanarayan
authors.initials: S
authors.lastname: Biswal
authors.affiliation: Defence Institute of High Altitude Research, C/o 56 APO, Leh-Ladakh, Jammu & Kashmir 901205, India.
authors.forename: Deepti
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Defence Institute of High Altitude Research, C/o 56 APO, Leh-Ladakh, Jammu & Kashmir 901205, India.
authors.forename: Kushal
authors.initials: K
authors.lastname: Kumar
authors.affiliation: Department of Anatomy, All India Institute of Medical Science, New Delhi, India.
authors.forename: Tapas Chandra
authors.initials: TC
authors.lastname: Nag
authors.affiliation: Defence Institute of High Altitude Research, C/o 56 APO, Leh-Ladakh, Jammu & Kashmir 901205, India.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Barhwal
authors.affiliation: Defence Institute of High Altitude Research, C/o 56 APO, Leh-Ladakh, Jammu & Kashmir 901205, India. Electronic address: drsunilhota@hotmail.com.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Hota
authors.affiliation: Defence Institute of High Altitude Research, C/o 56 APO, Leh-Ladakh, Jammu & Kashmir 901205, India.
authors.forename: Bhuvnesh
authors.initials: B
authors.lastname: Kumar
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D019588:Aging, Premature / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000150:complications*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000502:physiology*
keywords: Aging; Hippocampus; Hypoxia; Learning; Memory; S100A9