Exercise intensities modulate cognitive function in spontaneously hypertensive rats through oxidative mediated synaptic plasticity in hippocampus

Oxidative damage in the brain may lead to cognitive impairments. There was considerable debate regarding the beneficial effects of physical exercise on cognitive functions because exercise protocols have varied widely across studies. We investigated whether different exercise intensities alter performance on cognitive tasks. The experiment was performed on spontaneously hypertensive rats (6 months at the established phase of hypertension) distributed into 3 groups: sedentary, low‐intensity exercise and high‐intensity exercise. Systolic blood pressure measurements confirmed hypertension in spontaneously hypertensive rats. In comparison to normotensive Wistar‐Kyoto rats, sedentary spontaneously hypertensive rats had similar escape latencies and a similar preference for the correct quadrant in the probe trial. Compared to the sedentary group, the low‐intensity exercise group had significantly better improvements in spatial memory assessed by Morris water maze. Low‐intensity exercise was associated with attenuated reactive oxygen species, as measured by dihydroethidine fluorescence and nitrotyrosine staining in the dentate gyrus of the hippocampus. This was coupled with increased numbers of neurons and dendritic spines as well as a significant upregulation of synaptic density. In contrast, the beneficial effects of low‐intensity exercise are abolished in high‐intensity exercise as shown by increased free radical levels and an impairment in spatial memory. We concluded that exercise is an effective strategy to improve spatial memory in spontaneously hypertensive rats even at an established phase of hypertension. Low‐intensity exercise exhibited better improvement on cognitive deficits than high‐intensity exercise by attenuating free radical levels and improving downstream synaptic plasticity.

[1]  Tsung-Ming Lee,et al.  Exercise Intensities Modulate Cognitive Function in Spontaneously Hypertensive Rats Through Oxidative Mediated Synaptic Plasticity in Hippocampus , 2021, The FASEB Journal.

[2]  F. Lamb,et al.  TNFα and Reactive Oxygen Signaling in Vascular Smooth Muscle Cells in Hypertension and Atherosclerosis. , 2020, American journal of hypertension.

[3]  É. Thorin,et al.  Impact of pulse pressure on cerebrovascular events leading to age-related cognitive decline. , 2018, American journal of physiology. Heart and circulatory physiology.

[4]  Wenge Yang,et al.  Redox Mechanism of Reactive Oxygen Species in Exercise , 2016, Front. Physiol..

[5]  Jian Liu,et al.  Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats , 2016, Molecular medicine reports.

[6]  E. D. de Kloet,et al.  Immobility in the forced swim test is adaptive and does not reflect depression , 2015, Psychoneuroendocrinology.

[7]  S. Patterson.  Immune dysregulation and cognitive vulnerability in the aging brain: Interactions of microglia, IL-1β, BDNF and synaptic plasticity , 2015, Neuropharmacology.

[8]  V. Luine,et al.  The evolving role of dendritic spines and memory: Interaction(s) with estradiol , 2015, Hormones and Behavior.

[9]  Kristine Yaffe,et al.  Potential for primary prevention of Alzheimer's disease: an analysis of population-based data , 2014, The Lancet Neurology.

[10]  Elke Edelmann,et al.  Pre- and postsynaptic twists in BDNF secretion and action in synaptic plasticity , 2014, Neuropharmacology.

[11]  Yang Liu,et al.  Downregulation of caveolin-1 contributes to the synaptic plasticity deficit in the hippocampus of aged rats , 2013, Neural regeneration research.

[12]  M. dal Pai Silva,et al.  Heart failure-induced skeletal myopathy in spontaneously hypertensive rats. , 2013, International journal of cardiology.

[13]  Y. Fujiyoshi,et al.  Impaired synaptic clustering of postsynaptic density proteins and altered signal transmission in hippocampal neurons, and disrupted learning behavior in PDZ1 and PDZ2 ligand binding-deficient PSD-95 knockin mice , 2012, Molecular Brain.

[14]  N. Uysal,et al.  Age-related changes in apoptosis in rat hippocampus induced by oxidative stress , 2012, Biotechnic & histochemistry : official publication of the Biological Stain Commission.

[15]  M. Koike,et al.  Cardiac benefits of exercise training in aging spontaneously hypertensive rats , 2011, Journal of hypertension.

[16]  S. Powers,et al.  Exercise-induced oxidative stress in humans: cause and consequences. , 2011, Free radical biology & medicine.

[17]  V. Gudnason,et al.  The effect of midlife physical activity on cognitive function among older adults: AGES--Reykjavik Study. , 2010, The journals of gerontology. Series A, Biological sciences and medical sciences.

[18]  A. Irintchev,et al.  Improved reversal learning and working memory and enhanced reactivity to novelty in mice with enhanced GABAergic innervation in the dentate gyrus. , 2010, Cerebral cortex.

[19]  Xinkun Wang,et al.  Frontiers in Aging Neuroscience Aging Neuroscience Review Article , 2022 .

[20]  D. Costa-Miserachs,et al.  Effects of long-term voluntary exercise on learning and memory processes: dependency of the task and level of exercise , 2009, Behavioural Brain Research.

[21]  Shu-Ping Lee,et al.  Effects of tocotrienol-rich fraction on exercise endurance capacity and oxidative stress in forced swimming rats , 2009, European Journal of Applied Physiology.

[22]  F. Schaeffel,et al.  DETECTION OF BEHAVIORAL ALTERATIONS AND LEARNING DEFICITS IN MICE LACKING SYNAPTOPHYSIN , 2022 .

[23]  S. Moochhala,et al.  Involvement of ROS in BBB dysfunction , 2009, Free radical research.

[24]  B. McEwen.  Understanding the potency of stressful early life experiences on brain and body function. , 2008, Metabolism: clinical and experimental.

[25]  F. Veglio,et al.  Hypertension and Cognitive Function , 2008, Clinical and experimental hypertension.

[26]  A. Belló-Klein,et al.  Exercise intensity influences cell injury in rat hippocampal slices exposed to oxygen and glucose deprivation , 2006, Brain Research Bulletin.

[27]  L. Talbot,et al.  Cognitive Function in Normal‐Weight, Overweight, and Obese Older Adults: An Analysis of the Advanced Cognitive Training for Independent and Vital Elderly Cohort , 2006, Journal of the American Geriatrics Society.

[28]  M. Noble,et al.  Redox regulation of precursor cell function: insights and paradoxes. , 2005, Antioxidants & redox signaling.

[29]  M. Cousin,et al.  Tyrosine phosphorylation of synaptophysin in synaptic vesicle recycling. , 2005, Biochemical Society transactions.

[30]  T. Kaneko,et al.  The effects of moderate-, strenuous- and over-training on oxidative stress markers, DNA repair, and memory, in rat brain , 2005, Neurochemistry International.

[31]  S. Asha Devi,et al.  Swim exercise training and adaptations in the antioxidant defense system of myocardium of old rats: relationship to swim intensity and duration. , 2004, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[32]  M. Lynch,et al.  Synaptophysin immunogold labelling of synapses decreases in dentate gyrus of the hippocampus of aged rats , 2003, Brain Research.

[33]  C. Cotman,et al.  Exercise increases the vulnerability of rat hippocampal neurons to kainate lesion , 2003, Brain Research.

[34]  E. Klann,et al.  Potentiation of Hippocampal Synaptic Transmission by Superoxide Requires the Oxidative Activation of Protein Kinase C , 2002, The Journal of Neuroscience.

[35]  C. Gobatto,et al.  Maximal lactate steady state in rats submitted to swimming exercise. , 2001, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[36]  T. van Groen,et al.  Chronic, severe hypertension does not impair spatial learning and memory in Sprague-Dawley rats. , 2001, Learning & memory.

[37]  J. Quevedo,et al.  Lipid peroxidation in hippocampus early and late after status epilepticus induced by pilocarpine or kainic acid in Wistar rats , 2000, Neuroscience Letters.

[38]  F. Amenta,et al.  The hippocampus in spontaneously hypertensive rats: a quantitative microanatomical study , 2000, Neuroscience.

[39]  A. Craig,et al.  Postsynaptic Scaffolds of Excitatory and Inhibitory Synapses in Hippocampal Neurons: Maintenance of Core Components Independent of Actin Filaments and Microtubules , 2000, The Journal of Neuroscience.

[40]  B. Tomlinson,et al.  Superoxide dismutase gene expression and activity in the brain of spontaneously hypertensive rats and normotensive rats. , 1999, Chinese medical journal.

[41]  T. Shirao,et al.  Loss of proteins regulating synaptic plasticity in normal aging of the human brain and in Alzheimer disease. , 1999, Journal of neuropathology and experimental neurology.

[42]  F. Gage,et al.  Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus , 1999, Nature Neuroscience.

[43]  M. Matsuo,et al.  Oxidative injury of synapse and alteration of antioxidative defense systems in rats, and its prevention by vitamin E. , 1997, European journal of biochemistry.

[44]  J. Lawler,et al.  Changes in creatine kinase expression induced by exercise in borderline hypertensive rat hearts. , 1994, Clinical and experimental hypertension.

[45]  A. West.  Neurobehavioral studies of forced swimming: The role of learning and memory in the forced swim test , 1990, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[46]  S. Segovia,et al.  Learned immobility explains the behavior of rats in the forced swimming test , 1989, Physiology & Behavior.

[47]  R. Morris.  Developments of a water-maze procedure for studying spatial learning in the rat , 1984, Journal of Neuroscience Methods.

[48]  I. Fridovich,et al.  Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. , 1971, Analytical biochemistry.

[49]  K. Sunagawa,et al.  Calorie restriction improves cognitive decline via up-regulation of brain-derived neurotrophic factor: tropomyosin-related kinase B in hippocampus ofobesity-induced hypertensive rats. , 2015, International heart journal.

[50]  B. Gualano,et al.  Low-intensity swimming training does not improve hypertension in rats , 2013 .

[51]  R. Marttila,et al.  Oxygen toxicity protecting enzymes in the human brain , 2005, Journal of Neural Transmission.

[52]  J. Kaye,et al.  Differential loss of synaptic proteins in Alzheimer's disease: implications for synaptic dysfunction. , 2005, Journal of Alzheimer's disease : JAD.

[53]  Á. Oliveira,et al.  Influence of exercise training frequency on cardiac and hepatic oxidative stress in rats. , 2003, Experimental and clinical cardiology.

[54]  C. Olanow,et al.  An introduction to the free radical hypothesis in Parkinson's disease , 1992, Annals of neurology.

[55]  H. H. Draper,et al.  Malondialdehyde determination as index of lipid peroxidation. , 1990, Methods in enzymology.