Effects of exercise and diet change on cognition function and synaptic plasticity in high fat diet induced obese rats

Lipids in Health and Disease

Sunghwun Kang¹  Ki Soeng Jang²  So Young Park¹  Ki Ok Shin²  Jinhee Woo² 

[1] Departments of Pharmacology, Medical Sciences Research Institute, College of Medicine, Dong-A University, Busan, Korea;Department of Physical Education, Laboratory of Exercise Physiology, College of Sports Science, Dong-A University, 840 Hadan2-dong, Saha-gu, Busan, Korea

关键词: Memory span;    High fat diet;    Synaptic plasticity;    Cognition function;    Exercise;   

Others  :  829679
DOI  :  10.1186/1476-511X-12-144

 received in 2013-04-29, accepted in 2013-09-17,  发布年份 2013

【 摘 要 】

Background

Nutritional imbalance-induced obesity causes a variety of diseases and in particular is an important cause of cognitive function decline. This study was performed on Sprague Dawley (SD) rats with 13-weeks of high fat diet-induced obesity in connection to the effects of regular exercise and dietary control for 8 weeks on the synaptic plasticity and cognitive abilities of brain.

Methods

Four weeks-old SD rats were adopted classified into normal-normal diet-sedentary (NNS, n = 8), obesity-high fat diet-sedentary (OHS, n = 8), obesity-high fat diet-training (OHT, n = 8), obesity-normal diet-sedentary (ONS, n = 8) and obesity- normal diet-training (ONT, n = 8). The exercise program consisted of a treadmill exercise administered at a speed of 8 m/min for 1–4 weeks, and 14 m/min for 5–8 weeks. The Western blot method was used to measure the expression of NGF, BDNF, p38MAPK and p-p38MAPK proteins in hippocampus of the brain, and expressions of NGF, BDNF, TrkA, TrkB, CREB and synapsin1 mRNA were analyzed through qRT-PCR.

Results

The results suggest cognitive function-related protein levels and mRNA expression to be significantly decreased in the hippocampus of obese rats, and synaptic plasticity as well as cognitive function signaling sub-pathway factors were also significantly decreased. In addition, 8-weeks exercises and treatment by dietary change had induced significant increase of cognitive function-related protein levels and mRNA expression as well as synaptic plasticity and cognitive function signaling sub-pathway factors in obese rats. In particular, the combined treatment had presented even more positive effect.

Conclusions

Therefore, it was determined that the high fat diet-induced obesity decreases plasticity and cognitive function of the brain, but was identified as being improved by exercises and dietary changes. In particular, it is considered that regular exercise has positive effects on memory span and learning capacity unlike dietary control.

【 授权许可】

   
2013 Woo et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Rajala MW, Scherer PE: Minireview the adipocyte–at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 2003, 144:3765-3773.
• [2]Finkel T, Holbrook NJ: Oxidants, oxidative stress and the biology of ageing. Nature 2000, 408:239-247.
• [3]Woo J, Yeo NH, Shin KO, Lee HJ, Yoo J, Kang S: Antioxidant enzyme activities and DNA damage in children with type 1 diabetes mellitus after 12 weeks of exercise. Acta Paediatr 2010, 99:1263-1268.
• [4]Krieglstein K, Richter S, Farkas L, Schuster N, Dünker N, Oppenheim RW, Unsicker K: Reduction of endogenous transforming growth factors beta prevents ontogenetic neuron death. Nat Neurosci 2000, 3:1085-1090.
• [5]Vecsey CG, Baillie GS, Jaganath D, Havekes R, Daniels A, Wimmer M, Huang T, Brown KM, Li XY, Descalzi G, Kim SS, Chen T, Shang YZ, Zhuo M, Houslay MD, Abel T: Sleep deprivation impairs cAMP signalling in the hippocampus. Nature 2009, 461:1122-1125.
• [6]Wirth MJ, Brun A, Grabert J, Patz S, Wahle P: Accelerated dendritic development of rat cortical pyramidal cells and interneurons after biolistic transfection with BDNF and NT4/5. Development 2003, 130:5827-5838.
• [7]Cotman C, Engesser-Cesar C: Exercise enhances and protects brain function. Exerc Sport Sci Rev 2002, 30:75-79.
• [8]Woo J, Shin KO, Yoo JH, Park S, Kang S: The effects of detraining on blood adipokines and antioxidant enzyme in Korean overweight children. Eur J Pediatr 2012, 171:235-243.
• [9]Isacson O, Seo H, Lin L, Albeck D, Granholm AC: Alzheimer’s disease and Down’s syndrome: roles of APP, trophic factors and ACh. Trends Neurosci 2002, 25:79-84.
• [10]Chae CH, Jung SL, An SH, Park BY, Wang SW, Cho IH, Cho JY, Kim HT: Treadmill exercise improves cognitive function and facilitates nerve growth factor signaling by activating mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 in the streptozotocin-induced diabetic rat hippocampus. Neuroscience 2009, 164:1665-1673.
• [11]Wang C, Godar RJ, Billington CJ, Kotz CM: Chronic administraion of brain-derived neurotrophic factor in the hypothalamic paraventricular nucleus reverses obesity induced by high-fat diet. Am J Physiol Regul Integr Comp Physiol 2010, 298:R1320-R1332.
• [12]Yu Y, Wang Q, Huang XF: Energy-restricted pair-feeding normalizes low levels of brain-derived neurotrophic factor/tyrosine kinase B mRNA expression in the hippocampus, but not ventromedial hypothalamic nucleus, in diet-induced obese mice. Neuroscience 2009, 160:295-306.
• [13]Molteni R, Wu A, Vaynman S, Ying Z, Barnard RJ, Gomez-Pinilla F: Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor. Neuroscience 2004, 123:429-440.
• [14]Ziegler D, Siekierka-Kleiser E, Meyer B, Schweers M: Validation of a novel screening device (NeuroQuick) for quantitative assessment of small nerve fiber dysfunction as an early feature of diabetic polyneuropathy. Diabetes Care 2005, 28:1169-1174.
• [15]Kim JJ, Song EY, Kosten TA: Stress effects in the hippocampus: synaptic plasticity and memory. Stress 2006, 9:1-11.
• [16]Chen MJ, Nguyen TV, Pike CJ, Russo-Neustadt AA: Norepinephrine induces BDNF and activates the PI-3K and MAPK cascades in embryonic hippocampal neurons. Cell Signal 2006, 19:114-128.
• [17]Neeper SA, Gómez-Pinilla F, Choi J, Cotman CW: Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res 1996, 726:49-56.
• [18]Woo J, Shin KO, Yeo NH, Park SY, Kang S: The effects of treadmill training on neurotrophins and immediately early protein in obese rats. Korean J Life Sci 2011, 21:985-991.
• [19]Adlard PA, Engesser-Cesar C, Cotman CW: Mild stress facilitates learning and exercise improves retention in aged mice. Exp Gerontol 2011, 46:53-59.
• [20]Kramer AF, Hahn S, Cohen NJ, Banich MT, McAuley E, Harrison CR, Chason J, Vakil E, Bardell L, Boileau RA, Colcombe A: Ageing, fitness and neurocognitive function. Nature 1999, 400:418-419.
• [21]Friedland RP, Fritsch T, Smyth KA, Koss E, Lerner AJ, Chen CH, Petot GJ, Debanne SM: Patients with Alzheimer’s disease have reduced activities in midlife compared with healthy control-group members. Proc Natl Acad Sci U S A 2001, 98:3440-3445.
• [22]Laurin D, Verreault R, Lindsay J, MacPherson K, Rockwood K: Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch Neurol 2001, 58:498-504.
• [23]Gomez-Pinilla F, Zhuang Y, Feng J, Ying Z, Fan G: Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. Eur J Neurosci 2011, 33:383-390.
• [24]Sweatt JD: Experience-dependent epigenetic modifications in the central nervous system. Biol Psychiatry 2009, 65:191-197.
• [25]Uysal N, Tugyan K, Kayatekin BM, Acikgoz O, Bagriyanik HA, Gonenc S, Ozdemir D, Aksu I, Togcu A, Semin I: The effects of regular aerobic exercise in adolescent period on hippocampal neuron density, apoptosis and spatial memory. Neurosci Lett 2005, 383:241-245.
• [26]Zuccato C, Cattaneo E: Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 2009, 5:311-322.
• [27]Gao Y, Nikulina E, Mellado W, Filbin MT: Neurotrophins elevate cAMP to reach a threshold required to overcome inhibition by MAG through extracellular signal-regulated kinase-dependent inhibition of phosphodiesterase. J Neurosci 2003, 23:11770-11777.
• [28]Williams B, Granholm AC, Sambamurti K: Age-dependent loss of NGF signaling in the rat basal forebrain is due to disrupted MAPK activation. Neurosci Lett 2007, 413:110-114.
• [29]Aguiar AS Jr, Castro AA, Moreira EL, Glaser V, Santos AR, Tasca CI, Latini A, Prediger RD: Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats: involvement of hippocampal plasticity via AKT, CREB and BDNF signaling. Mech Ageing Dev 2011, 132:560-567.
• [30]Shen H, Tong L, Balazs R, Cotman CW: Physical activity elicits sustained activation of the cyclic AMP response element-binding protein and mitogen-activated protein kinase in the rat hippocampus. Neuroscience 2001, 107:219-229.
• [31]Lyons WE, Mamounas LA, Ricaurte GA, Coppola V, Reid SW, Bora SH, Wihler C, Koliatsos VE, Tessarollo L: Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc Natl Acad Sci USA 1999, 96:15239-15244.
• [32]Wang T, Xie K, Lu B: Neurotrophins promote maturation of developing neuromuscular synapses. J Neurosci 1995, 15:4796-4805.
• [33]Jovanovic JN, Czernik AJ, Fienberg AA, Greengard P, Sihra TS: Synapsins as mediators of BDNF-enhanced neurotransmitter release. Nat Neurosci 2000, 3:323-329.
• [34]Vaynman S, Ying Z, Gomez-Pinilla F: Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 2004, 20:2580-2590.
• [35]Vaynman S, Ying Z, Gomez-Pinilla F: The select action of hippocampal calcium calmodulin protein kinase II in mediating exercise-enhanced cognitive function. Neuroscience 2007, 144:825-833.
• [36]Badowska-Szalewska E, Spodnik E, Klejbor I, Ludkiewicz B, Moryś J: Do two models of acute and chronic stress stimulation influence the amount of nerve growth factor (NGF) and its receptor TrkA in the hippocampal neurons of middle aged rats? Brain Res 2011, 1384:97-109.