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Effects of Forced Running Exercise on Cognitive Function and Its Relation to Zinc Homeostasis-Related Gene Expression in Rat Hippocampus

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Abstract

Voluntary exercise has been implicated to be beneficial for overall health and cognitive function in both clinical and experimental studies, but little is presently known about forced physical exercise on cognition and underlying molecular mechanism. We have used real-time RT-PCR to analyze gene expression in hippocampus, in the presence and absence of physical exercise, during spatial learning of rats in the Morris water maze. Our results show distinct zinc homeostasis-related gene expression profiles associated with learning and memory. Rats with physical exercise (EXP) showed a significant up-regulation of mRNA expression of zinc transporter-2 (ZnT-2), ZnT-4, ZnT-5, ZnT-6, and ZnT-7, metallothionein-1 (MT-1)–MT-3, divalent cation transporter-1, and Zrt-Irt-like proteins-7 in hippocampus when compared with control rats. In addition, spatial learning ability was improved in EXP rats compared with that in control group. This study provides the first comparative view of zinc homeostasis-related gene expression in hippocampus following forced physical exercise. These results suggested that forced physical exercise may provide a simple means to maintain brain function and promote learning capacity. Results of this study also suggest that exercise mobilizes zinc homeostasis-related gene expression profiles that would be predicted to benefit brain plasticity processes.

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References

  1. Cotman CW, Berchtold NC (2002) Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 25:295–301

    Article  PubMed  CAS  Google Scholar 

  2. Dishman RK, Berthoud HR, Booth FW et al (2006) Neurobiology of exercise. Obesity 14:345–356

    Article  PubMed  CAS  Google Scholar 

  3. Farmer JX, Zhao H, van Praag K et al (2004) Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague–Dawley rats in vivo. Neuroscience 124:71–79

    Article  PubMed  CAS  Google Scholar 

  4. Fox SM III, Naughton JP, Haskell WL et al (1971) Physical activity and the prevention of coronary heart disease. Ann Clin Res 3:404–432

    PubMed  Google Scholar 

  5. Griesbach GS, Gómez-Pinilla FD, Hovda A (2007) Time window for voluntary exercise-induced increases in hippocampal neuroplasticity molecules after traumatic brain injury is severity dependent. J Neurotrauma 24:1161–1171

    Article  PubMed  Google Scholar 

  6. Ying Z, Roy RR, Edgerton VR et al (2005) Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury. Exp Neurol 193:411–419

    Article  PubMed  CAS  Google Scholar 

  7. Gómez-Pinilla F, So V, Kesslak JP (1998) Spatial learning and physical activity contribute to the induction of fibroblast growth factor: neural substrates for increased cognition associated with exercise. Neuroscience 85:53–61

    Article  PubMed  Google Scholar 

  8. Schweitzer NB, Alessio HM, Berry SD et al (2006) Exercise-induced changes in cardiac gene expression and its relation to spatial maze performance. Neurochem Int 48:9–16

    Article  PubMed  CAS  Google Scholar 

  9. Widenfalk J, Olson L, Thorén P (1999) Deprived of habitual running, rats downregulate BDNF and TrkB messages in the brain. Neurosci Res 34:125–132

    Article  PubMed  CAS  Google Scholar 

  10. Alaei HA, Borjeian L, Azizi M et al (2006) Treadmill running reverses retention deficit induced by morphine. Eur J Pharmacol 536:138–141

    Article  PubMed  CAS  Google Scholar 

  11. Albeck DS, Sano K, Prewitt GE et al (2006) Mild forced treadmill exercise enhances spatial learning in the aged rat. Behav Brain Res 168:345–348

    Article  PubMed  Google Scholar 

  12. Ang ET, Dawe GS, Wong PT et al (2006) Alterations in spatial learning and memory after forced exercise. Brain Res 1113:186–193

    Article  PubMed  CAS  Google Scholar 

  13. Winter B, Breitenstein C, Mooren FC et al (2007) High impact running improves learning. Neurobiol Learn Mem 87:597–609

    Article  PubMed  Google Scholar 

  14. Saadipour K, Sarkaki A, Alaei H et al (2009) Forced exercise improves passive avoidance memory in morphine-exposed rats. Pak J Biol Sci 12:1206–1211

    Article  PubMed  CAS  Google Scholar 

  15. Yuede CM, Zimmerman SD, Dong H et al (2009) Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer's disease. Neurobiol Dis 35:426–432

    Article  PubMed  CAS  Google Scholar 

  16. Ni H, Li C, Tao LY et al (2009) Physical exercise improves learning by modulating hippocampal mossy fiber sprouting and related gene expression in a developmental rat model of penicillin-induced recurrent epilepticus. Toxicol Lett 191:26–32

    Article  PubMed  CAS  Google Scholar 

  17. Ni H, Jiang YW, Jiang WM et al (2009) Effects of physical exercise on the developmental expression of hippocampal zinc transporter 1 and glutamate receptor subunit 2, and on cognitive function in a rat model of recurrent neonatal seizure. Neural Regen Res 4:20–25

    Google Scholar 

  18. Ni H, Jiang YW, Tao LY et al (2009) ZnT-1, ZnT-3, CaMKII, PRG-1 expressions in hippocampus following neonatal seizure-induced cognitive deficit in rats. Toxicol Lett 184:145–150

    Article  PubMed  CAS  Google Scholar 

  19. Johnson MR, Wang K, Smith JB et al (2000) Quantitation of dihydropyrimidine dehydrogenase expression by real-time reverse transcription polymerase chain reaction. Anal Biochem 278:175–184

    Article  PubMed  CAS  Google Scholar 

  20. Chen HI, Lin LC, Yu L (2008) Treadmill exercise enhances passive avoidance learning in rats: the role of down-regulated serotonin system in the limbic system. Neurobiol Learn Mem 89:489–496

    Article  PubMed  CAS  Google Scholar 

  21. Murakami M, Hirano T (2008) Intracellular zinc homeostasis and zinc signaling. Cancer Sci 99:1515–1522

    Article  PubMed  CAS  Google Scholar 

  22. Ni H (2006) Seizure-induced brain injury in brain development and Zn2+ metastasis in hippocampus. Sheng Li Ke Xue Jin Zhan 37:331–334

    PubMed  CAS  Google Scholar 

  23. Colvin RA, Bush AI, Volitakis I et al (2008) Insights into Zn2+ homeostasis in neurons from experimental and modeling studies. Am J Physiol Cell Physiol 294:C726–C742

    Article  PubMed  CAS  Google Scholar 

  24. Williams BL, Yaddanapudi K, Kirk CM et al (2006) Metallothioneins and zinc dysregulation contribute to neurodevelopmental damage in a model of perinatal viral infection. Brain Pathol 16:1–14

    Article  PubMed  CAS  Google Scholar 

  25. Colvin RA, Fontaine CP, Laskowski M et al (2003) Zn2+ transporters and Zn2+ homeostasis in neurons. Eur J Pharmacol 479:171–185

    Article  PubMed  CAS  Google Scholar 

  26. Lichten LA, Cousins RJ (2009) Mammalian zinc transporters: nutritional and physiologic regulation. Annu Rev Nutr 29:153–176

    Article  PubMed  Google Scholar 

  27. Mims MP, Prchal JT (2005) Divalent metal transporter 1. Hematology 10:339–345

    Article  PubMed  CAS  Google Scholar 

  28. Gunshin H, Mackenzie B, Berger UV et al (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388:482–488

    Article  PubMed  CAS  Google Scholar 

  29. Chowanadisai W, Lönnerdal B, Kelleher SL (2008) Zip6 (LIV-1) regulates zinc uptake in neuroblastoma cells under resting but not depolarizing conditions. Brain Res 1199:10–19

    Article  PubMed  CAS  Google Scholar 

  30. Ebadi M, Brown-Borg H, El Refaey H et al (2005) Metallothionein-mediated neuroprotection in genetically engineered mouse models of Parkinson's disease. Brain Res Mol Brain Res 134:67–75

    Article  PubMed  CAS  Google Scholar 

  31. Pedersen MØ, Jensen R, Pedersen DS et al (2009) Metallothionein-I+II in neuroprotection. Biofactors 35:315–325

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (30470555 and 30870808), the Natural Science Foundation of Jiangsu Province of China (BK2007509, 07KJB320103).

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Authors and Affiliations

  1. Neurology Laboratory, The Children’s Hospital Affiliated to Soochow University, No.303, Jingde Road, 215003, Suzhou, People’s Republic of China

    Hong Ni, Chao Li, Xing Feng & Jian-nong Cen

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  1. Hong Ni
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  2. Chao Li
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  3. Xing Feng
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  4. Jian-nong Cen
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Correspondence to Hong Ni.

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Ni, H., Li, C., Feng, X. et al. Effects of Forced Running Exercise on Cognitive Function and Its Relation to Zinc Homeostasis-Related Gene Expression in Rat Hippocampus. Biol Trace Elem Res 142, 704–712 (2011). https://doi.org/10.1007/s12011-010-8793-z

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  • DOI: https://doi.org/10.1007/s12011-010-8793-z

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