Antioxidant responses to chronic hypoxia in the rat cerebellum and pons

Abstract

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH) and sleep fragmentation and deprivation. Exposure to CIH results in oxidative stress in the cortex, hippocampus and basal forebrain of rats and mice. We show that sustained and intermittent hypoxia induces antioxidant responses, an indicator of oxidative stress, in the rat cerebellum and pons. Increased glutathione reductase (GR) activity and thiobarbituric acid reactive substance (TBARS) levels were observed in the pons and cerebellum of rats exposed to CIH or chronic sustained hypoxia (CSH) compared with room air (RA) controls. Exposure to CIH or CSH increased GR activity in the pons, while exposure to CSH increased the level of TBARS in the cerebellum. The level of TBARS was increased to a greater extent after exposure to CSH than to CIH in the cerebellum and pons. Increased superoxide dismutase activity (SOD) and decreased total glutathione (GSHt) levels were observed after exposure to CIH compared with CSH only in the pons. We have previously shown that prolonged sleep deprivation decreased SOD activity in the rat hippocampus and brainstem, without affecting the cerebellum, cortex or hypothalamus. We therefore conclude that sleep deprivation and hypoxia differentially affect antioxidant responses in different brain regions.

Fig. 1

Thiobarbituric acid reactive substance (TBARS) levels in the (a) cerebellum and (b) pons of rats exposed to room air (RA, n = 6), chronic intermittent hypoxia (CIH, diamonds, n = 6/time point) or chronic sustained hypoxia (CSH, squares, n = 6/time point). Bars represent standard error. (‡p < 0.05, ‡‡‡p < 0.001, CSH vs. RA; *p < 0.05, **p < 0.01 CSH vs. CIH, post-hoc Bonferroni.) Normalized RA values for cerebellum = 0.77 ± 0.06 and pons = 0.97 ± 0.06.

Fig. 2

(a) Glutathione reductase (GR) activity (b) superoxide dismutase (SOD) activity and (c) total glutathione (GSHt) levels in the pons of rats exposed to room air (RA, n = 6), chronic intermittent hypoxia (CIH, diamonds, n = 6/time point) or chronic sustained hypoxia (CSH, squares, n = 6/time point). Bars represent standard error. (‡p < 0.05, CSH vs. RA; †p < 0.05, CIH vs. RA, post-hoc Bonferroni.) (*p < 0.05, **p < 0.01, ***p < 0.001, CSH vs. CIH, post-hoc Bonferroni). Normalized RA values for GR activity = 0.83 ± 0.07, SOD activity = 1.04 ± 0.07 and GSHt levels = 1.02 ± 0.06.