Exercise prevents sleep deprivation-associated anxiety-like behavior in rats: Potential role of oxidative stress mechanisms

Our previous work suggests that pharmacological induction of oxidative stress causes anxiety-like behavior in rats. Interestingly, sleep deprivation is reported to cause oxidative damage in the brain and is also reported to be anxiogenic. Minimal mechanistic insights are available. In this study, using a behavioral and biochemical approach, we investigated involvement of oxidative stress mechanisms in sleep deprivation-induced anxiety-like behavior of rats and the protective role of treadmill exercise in this process. We report that acute sleep deprivation (SD) increases oxidative stress in the cortex, hippocampus and amygdala while prior treadmill exercise prevents this increase. Serum corticosterones also increase with SD but its levels are normalized in exercised sleep-deprived rats. Also, anxiety-like behavior of rats significantly increases with SD while prior treadmill exercise prevents this increase. Protein expression of two enzymes involved in antioxidant defense, glyoxalase (GLO)-1 and glutathione reductase (GSR)-1 increased after 24h SD in the hippocampus, cortex and amygdala while their levels were normalized in exercised sleep-deprived rats. It is plausible that oxidative stress via regulation of GLO1 and GSR1 is involved in sleep deprivation-induced anxiety-like behavior of rats.

[1]  R. Post,et al.  Effects of one night's sleep deprivation on mood and behavior in panic disorder. Patients with panic disorder compared with depressed patients and normal controls. , 1986, Archives of general psychiatry.

[2]  Y. Khadrawy,et al.  Effect of oxidative stress induced by paradoxical sleep deprivation on the activities of Na+, K+-ATPase and acetylcholinesterase in the cortex and hippocampus of rat. , 2011, Translational research : the journal of laboratory and clinical medicine.

[3]  Z. Xia,et al.  Oxidative stress: A potential recipe for anxiety, hypertension and insulin resistance , 2010, Brain Research.

[4]  Eric E. Schadt,et al.  Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice , 2005, Nature.

[5]  M. Uchiyama,et al.  Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. , 1978, Analytical biochemistry.

[6]  D. Kupfer,et al.  Total prolonged drug-induced REM sleep suppression in anxious-depressed patients. , 1971, Archives of general psychiatry.

[7]  P. K. Smith,et al.  Measurement of protein using bicinchoninic acid. , 1985, Analytical biochemistry.

[8]  E. Callaway,et al.  Combined effects of alcohol and sleep deprivation in normal young adults , 2004, Psychopharmacology.

[9]  S. Salim,et al.  Moderate treadmill exercise prevents oxidative stress-induced anxiety-like behavior in rats , 2010, Behavioural Brain Research.

[10]  F. Holsboer,et al.  Identification of Glyoxalase-I as a Protein Marker in a Mouse Model of Extremes in Trait Anxiety , 2005, The Journal of Neuroscience.

[11]  D. Sharma,et al.  Effect of paradoxical sleep deprivation on oxidative stress parameters in brain regions of adult and old rats , 2008, Biogerontology.

[12]  A. Beaudet,et al.  Alpha7 nicotinic receptor subunits are not necessary for hippocampal-dependent learning or sensorimotor gating: a behavioral characterization of Acra7-deficient mice. , 1998, Learning & memory.

[13]  A. Zharkovsky,et al.  Small platform stress attenuates the anxiogenic effect of diazepam withdrawal in the plus-maze test , 1998, Behavioural Brain Research.

[14]  A. Pack,et al.  Cumulative sleepiness, mood disturbance, and psychomotor vigilance performance decrements during a week of sleep restricted to 4-5 hours per night. , 1997, Sleep.

[15]  B. Halliwell,et al.  Free radicals in biology and medicine , 1985 .

[16]  A. Zharkovsky,et al.  The Effects of Drugs Acting at GABA-Benzodiazepine-Barbiturate Receptor Complex on the Behaviour of Sleep-Deprived Mice , 1995 .

[17]  R. Garg,et al.  Possible role of trazodone and imipramine in sleep deprivation-induced anxiety-like behavior and oxidative damage in mice. , 2009, Methods and findings in experimental and clinical pharmacology.

[18]  S. Tufik,et al.  Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice , 2004, Neuropharmacology.

[19]  S. Tufik,et al.  Anxiogenic effect of sleep deprivation in the elevated plus-maze test in mice , 2004, Psychopharmacology.

[20]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[21]  本多 和樹 Oxidized glutathione regulates physiological sleep in unrestrained rats , 1994 .

[22]  André Charles,et al.  Effects of sleep deprivation on Color-Word, Emotional, and Specific Stroop interference and on self-reported anxiety , 2006, Brain and Cognition.

[23]  D. Treit,et al.  Effects of centrally administered anxiolytic compounds in animal models of anxiety , 1999, Neuroscience & Biobehavioral Reviews.

[24]  Li Li Ji,et al.  Sleep deprivation and cellular responses to oxidative stress. , 2004, Sleep.

[25]  Adrian H. Taylor Physical activity, anxiety, and stress , 2001 .

[26]  Chronic caffeine treatment prevents sleep deprivation-induced impairment of cognitive function and synaptic plasticity. , 2010, Sleep.

[27]  J. Siegel,et al.  Sleep deprivation decreases superoxide dismutase activity in rat hippocampus and brainstem , 2002, Neuroreport.

[28]  P. Burghardt,et al.  The effects of chronic treadmill and wheel running on behavior in rats , 2004, Brain Research.

[29]  Michael Davis,et al.  Neural systems involved in fear and anxiety measured with fear-potentiated startle. , 2006, The American psychologist.

[30]  A. Zharkovsky,et al.  The effects of flumazenil, Ro 15-4513 and beta-CCM on the behaviour of control and stressed mice in the plus-maze test. , 1997, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[31]  A. Coenen,et al.  Paradoxical sleep deprivation and locomotor activity in rats , 1981, Physiology & Behavior.

[32]  A. Dunn,et al.  Increased open field locomotion and decreased striatal GABAA binding after activity wheel running , 1996, Physiology & Behavior.

[33]  Paul J Thornalley Unease on the role of glyoxalase 1 in high-anxiety-related behaviour. , 2006, Trends in molecular medicine.

[34]  Effect of short sleep duration on daily activities--United States, 2005-2008. , 2011, MMWR. Morbidity and mortality weekly report.

[35]  R. Muñoz Anxiety disorders. , 1986, New directions for mental health services.

[36]  A. Zharkovsky,et al.  Ro 15-4513 potentiates, instead of antagonizes, ethanol-induced sleep in mice exposed to small platform stress. , 1996, European journal of pharmacology.

[37]  Stephen Maren,et al.  Pavlovian fear conditioning as a behavioral assay for hippocampus and amygdala function: cautions and caveats , 2008, The European journal of neuroscience.

[38]  P Salmon,et al.  Effects of physical exercise on anxiety, depression, and sensitivity to stress: a unifying theory. , 2001, Clinical psychology review.

[39]  Anil Kumar,et al.  Protective effect of Withania somnifera Dunal on the behavioral and biochemical alterations in sleep-disturbed mice (Grid over water suspended method). , 2007, Indian journal of experimental biology.

[40]  D. Rujescu,et al.  Candidate genes of anxiety-related behavior in HAB/LAB rats and mice: Focus on vasopressin and glyoxalase-I , 2007, Neuroscience & Biobehavioral Reviews.

[41]  A. Altamura,et al.  Serotonin norepinephrine reuptake inhibitors (SNRIs) in anxiety disorders: a comprehensive review of their clinical efficacy , 2010, Human psychopharmacology.

[42]  Onofrio Resta,et al.  8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy. , 2003, Chest.

[43]  F. Holsboer,et al.  Protein Biomarkers in a Mouse Model of Extremes in Trait Anxiety* , 2006, Molecular & Cellular Proteomics.

[44]  G. Gessa,et al.  Sleep deprivation in the rat: an animal model of mania , 1995, European Neuropsychopharmacology.

[45]  J. Leasure,et al.  Forced and voluntary exercise differentially affect brain and behavior , 2008, Neuroscience.

[46]  C. Cirelli Cellular consequences of sleep deprivation in the brain. , 2006, Sleep medicine reviews.

[47]  M. Ikeda,et al.  Brain oxidation is an initial process in sleep induction , 2005, Neuroscience.

[48]  S. Rauch,et al.  Amygdala, Medial Prefrontal Cortex, and Hippocampal Function in PTSD , 2006, Annals of the New York Academy of Sciences.

[49]  M. De la Fuente,et al.  Impairment of several immune functions in anxious women. , 2007, Journal of psychosomatic research.

[50]  C. Dessauer,et al.  Analysis of the interaction between RGS2 and adenylyl cyclase. , 2004, Methods in enzymology.

[51]  N. Okamura,et al.  Roles of hypothalamic subgroup histamine and orexin neurons on behavioral responses to sleep deprivation induced by the treadmill method in adolescent rats. , 2010, Journal of pharmacological sciences.

[52]  Huda Akil,et al.  Neural circuits mediating stress , 1999, Biological Psychiatry.

[53]  Stuart J. H. Biddle,et al.  Physical Activity and Psychological Well-Being , 2021, Psychology of Physical Activity.

[54]  E. Shacter,et al.  Differential susceptibility of plasma proteins to oxidative modification: examination by western blot immunoassay. , 1994, Free radical biology & medicine.

[55]  E. Reimund The free radical flux theory of sleep. , 1994, Medical hypotheses.

[56]  F. Goodwin,et al.  Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines , 1980, Pharmacology Biochemistry and Behavior.

[57]  E. Pereira,et al.  Integrating the open field, elevated plus maze and light/dark box to assess different types of emotional behaviors in one single trial , 2008, Behavioural Brain Research.

[58]  J. Nobrega,et al.  Sleep deprivation induces brain region‐specific decreases in glutathione levels , 1998, Neuroreport.

[59]  A. Rechtschaffen,et al.  Mammalian sleep, longevity, and energy metabolism. , 1974, Brain, behavior and evolution.

[60]  J. A. Horne,et al.  A review of the biological effects of total sleep deprivation in man , 1978, Biological Psychology.

[61]  Anil Kumar,et al.  Possible involvement of GABAergic mechanism in protective effect of melatonin against sleep deprivation–induced behaviour modification and oxidative damage in mice , 2009, Fundamental & clinical pharmacology.

[62]  S. Tufik,et al.  Hormonal and Behavioural Responses of Paradoxical Sleep‐Deprived Rats to the Elevated Plus Maze , 2002, Journal of neuroendocrinology.

[63]  R. Salas,et al.  Progesterone modulation of α5 nAChR subunits influences anxiety‐related behavior during estrus cycle , 2009, Genes, brain, and behavior.