Skip to main content

Advertisement

SpringerLink
Log in

Strength and Aerobic Exercises Improve Spatial Memory in Aging Rats Through Stimulating Distinct Neuroplasticity Mechanisms

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Aging is associated with impaired cognition and memory and increased susceptibility to neurodegenerative disorders. Physical exercise is neuroprotective; however, the major evidence of this effect involves studies of only aerobic training in young animals. The benefits of other exercise protocols such as strength training in aged animals remains unknown. Here, we investigated the effect of aerobic and strength training on spatial memory and hippocampal plasticity in aging rats. Aging Wistar rats performed aerobic or strength training for 50 min 3 to 4 days/week for 8 weeks. Spatial memory and neurotrophic and glutamatergic signaling in the hippocampus of aged rats were evaluated after aerobic or strength training. Both aerobic and strength training improved cognition during the performance of a spatial memory task. Remarkably, the improvement in spatial memory was accompanied by an increase in synaptic plasticity proteins within the hippocampus after exercise training, with some differences in the intracellular functions of those proteins between the two exercise protocols. Moreover, neurotrophic signaling (CREB, BDNF, and the P75NTR receptor) increased after training for both exercise protocols, and aerobic exercise specifically increased glutamatergic proteins (NMDA receptor and PSD-95). We also observed a decrease in DNA damage after aerobic training. In contrast, strength training increased levels of PKCα and the proinflammatory factors TNF-α and IL-1β. Overall, our results show that both aerobic and strength training improved spatial memory in aging rats through inducing distinct molecular mechanisms of neuroplasticity. Our findings extend the idea that exercise protocols can be used to improve cognition during aging.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.

Similar content being viewed by others

References

  1. Mattson MP, Magnus T (2006) Ageing and neuronal vulnerability. Nat Rev Neurosci 7:278–228. doi:10.1038/nrn1886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Farooqui T, Farooqui AA (2009) Aging: an important factor for the pathogenesis of neurodegenerative diseases. Mech Ageing Dev 129:203–215. doi:10.1016/j.mad.2008.11.006

    Article  Google Scholar 

  3. Glorioso C, Sibille E (2009) Between destiny and disease: genetics and molecular pathways of human central nervous system aging. Prog Neurobiol 93:165–181. doi:10.1016/j.pneurobio.2010.11.006

    Article  Google Scholar 

  4. Freitas AA, Vasieva O, Magalhaes JP (2011) A data mining approach for classifying DNA repair genes into ageing-related or non-ageing-related. BMC Genomics 12:27. doi:10.1186/1471-2164-12-27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lombard DB, Chua KF, Mostoslavsky R, Franco S, Gostissa M, Alt FW (2005) DNA repair, genome stability, and aging. Cell 120:497–512. doi:10.1016/j.cell.2005.01.028

    Article  CAS  PubMed  Google Scholar 

  6. Lambert TJ, Fernandez SM, Frick KM (2005) Different types of environmental enrichment have discrepant effects on spatial memory and synaptophysin evels in female mice. Neurobiol Learn Mem 83:206–216. doi:10.1016/j.nlm.2004.12.001

    Article  CAS  PubMed  Google Scholar 

  7. Molteni R, Ying Z, Gomez-Pinilla F (2002) Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray. Eur J Neurosci 16:1107–1116. doi:10.1046/j.1460-9568.2002.02158

    Article  PubMed  Google Scholar 

  8. van Praag H, Shubert T, Zhao C, Gage FH (2005) Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25:8680–8685. doi:10.1523/jneurosci.1730-05.2005

    Article  PubMed  PubMed Central  Google Scholar 

  9. Muller AP, Gnoatto J, Moreira JD, Zimmer ER, Haas CB, Lulhier F, Perry ML, Souza DO et al (2011) Exercise increases insulin signaling in the hippocampus: physiological effects and pharmacological impact of intracerebroventricular insulin administration in mice. Hippocampus 21:1082–1092. doi:10.1002/hipo.20822

    Article  CAS  PubMed  Google Scholar 

  10. Tuon T, Valvassori SS, Lopes-Borges J, Luciano T, Trom CB, Silva LA, Quevedo J, Souza CT et al (2012) Physical training exerts neuroprotective effects in the regulation of neurochemical factors in an animal model of Parkinson’s disease. Neuroscience 227:295–302. doi:10.1016/j.neuroscience.2012.09.063

    Article  Google Scholar 

  11. Radak Z, Toldy A, Szabo Z, Siamilis S, Nyakas C, Silye G, Jakus J, Goto S (2006) The effects of training and detraining on memory, neurotrophins and oxidative stress markers in rat brain. Neurochem Int 49:387–392. doi:10.1016/j.neuint.2006.02.004

    Article  CAS  PubMed  Google Scholar 

  12. Portugal EMM, Cevada T, Monteiro-Junior RS, Teixeira Guimarães T, da Cruz RE, Lattari E, Blois C, Camaz Deslandes A (2013) Neuroscience of exercise: from neurobiology mechanisms to mental health. Neuropsychobio 68(1):1–14. doi:10.1159/000340946

    Article  Google Scholar 

  13. Westcott WL (2012) Resistance training is medicine: effects of strength training on health. Curr Sports Med Rep 11(4):209–216. doi:10.1249/JSR.0b013e30825dabb8

    Article  PubMed  Google Scholar 

  14. Eadie BD, Redila VA, Christie BR (2005) Voluntary exercise alters the cytoarchitecture of the adult dentate gyrus by increasing cellular proliferation, dendritic complexity, and spine density. J Comp Neurol 486:39–47. doi:10.1002/cne.20493

    Article  PubMed  Google Scholar 

  15. van Praag H, Christie BR, Sejnowski TJ, Gage FH (1999) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A 96:13327–13330

    Google Scholar 

  16. van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH (2002) Functional neurogenesis in the adult hippocampus. Nature 2002; 415:1029–1033. doi: 10.1038/4151029a

  17. Archer T (2011) Physical exercise alleviates debilities of normal aging and Alzheimer’s disease. Acta Neurol Scand 123:221–238. doi:10.1111/j.1600-0404.2010.01412.x

    Article  CAS  PubMed  Google Scholar 

  18. Gligoroska JP, Manchevska S (2012) The effect of physical activity on cognition - physiological mechanisms. Mater Sociomed 24:198–202. doi:10.5455/msm.2012.24.198-202

    Article  PubMed  PubMed Central  Google Scholar 

  19. Yoshii A, Constantine-Paton M (2007) BDNF induces transport of PSD-95 to dendrites through PI3K- AKT signaling after NMDA receptor activation. Nat Neurosci 10(6):702–711. doi:10.1038/nn1903

    Article  CAS  PubMed  Google Scholar 

  20. Neeper SA, Gomez-Pinilla F, Choi J, Cotman C (1995) Exercise and brain neurotrophins. Nature 373:109. doi:10.1038/373009a0

    Article  CAS  PubMed  Google Scholar 

  21. Mattson MP, Maudsley S, Martin B (2004) BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurode-generative disorders. Trends Neurosci 27:589–594. doi:10.1016/j.tins.2004.08.001

    Article  CAS  PubMed  Google Scholar 

  22. Li Y, Luikart BW, Birnbaum S, Chen J, Kwon CH, Kernie SG, Bassel-Duby R, Parada LF (2008) TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron 59:399–412. doi:10.1016/j.neuron.2008.06.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Marais L, Stein DJ, Daniels WM (2009) Exercise increases BDNF levels in the striatum and decreases depressive-like behavior in chronically stressed rats. Metab Brain Dis 24:587–597. doi:10.1007/s11011-009-9157-2

    Article  CAS  PubMed  Google Scholar 

  24. Aguiar AS Jr, Castro AA, Moreira EL, Glaser V, Santos AR, Tasca CI, Latini A, Prediger RD (2011) 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 131:560–567. doi:10.1016/j.mad.2011.09.005

    Article  Google Scholar 

  25. Mora F, Segovia G, del Arco A (2007) Aging, plasticity and environmental enrichment: structural changes and neurotransmitter dynamics in several areas of the brain. Brain Res Rev 55(1):78–88. doi:10.1016/j.brainresrev.2007.03.011

    Article  CAS  PubMed  Google Scholar 

  26. Redila VA, Olson AK, Swann SE, Mohades G, Webber AJ, Weinberg J, Christie BR (2006) Hippocampal cell proliferation is reduced following prenatal ethanol exposure but can be rescued with voluntary exercise. Hippocampus 16:295–301. doi:10.1002/hipo.20164

    Article  Google Scholar 

  27. Hongpaisan J, Xu C, Sen A, Nelson TJ, Alkon DL (2013) PKC activation during training restores mushroom spine synapses and memory in the aged rat. Neurobiol Dis 55:44–62. doi:10.1016/j.nbd.2013.03.012

    Article  CAS  PubMed  Google Scholar 

  28. Tan S-L, Parker PJ (2003) Emerging and diverse roles of protein kinase C in immune cell signalling. Biochem J 376:545–552. doi:10.1042/BJ20030406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kumar A (2015) NMDA receptor function during senescence: implication on cognitive performance. Front Neurosci 9:473. doi:10.3289/fnins.2015.00473

    PubMed  PubMed Central  Google Scholar 

  30. El-Husseini E, Schnell DM, Chetkovich RA, Nicoll DS (2000) PSD-95 involvement in maturation of excitatory synapses. Science 280:1354–1358. doi:10.1126/science.280.5495.1354

    Google Scholar 

  31. Migaud P, Charlesworth M, Dempster LC, Webster AM, Watabe M, Makhinson Y, He MF, Ramsay RG, Morris JH, Morrison et al. (1998) Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature 396: 432–439. doi: 10.1038/24790

  32. Beique JC, Andrade R (2003) PSD-95 regulates synaptic transmission and plasticity in rat cerebral córtex J. Physiol 546:859–867. doi:10.1113/jphysiol.2002.030359

    Article  CAS  Google Scholar 

  33. Nithianantharajah J, Levis H, Murphy M (2004) Environmental enrichment results in cortical and subcortical changes in levels of synaptophysin and PSD-95 proteins. Neurobiol Learn Mem 81:200–210. doi:10.1016/j.nlm.2004.02.002

    Article  CAS  PubMed  Google Scholar 

  34. Mourão FA, Leite HR, de Carvalho LE, Ferreira E, Vieira TH, Pinto MC, de Castro Medeiros D, Andrade IL et al (2014) Neuroprotective effect of exercise in rat hippocampal slices submitted to in vitro ischemia is promoted by decrease of glutamate release and pro-apoptotic markers. J Neurochem 130(1):65–73. doi:10.1111/jnc.12786

    Article  Google Scholar 

  35. Hornberger TA, Jr Farrar RP (2004) Physiological hypertrophy of the FHL muscle following 8 weeks of progressive resistance exercise in the rat. Can J Appl Physiol 28(1):16–30

    Article  Google Scholar 

  36. Scheffer DL, Silva LA, Tromm CB, da Rosa GL, Silveira PC, de Souza CT, Latini A, Pinho RA (2012) Impact of different resistance training protocols on muscular oxidative stress parameters. Appl Physiol Nutr Metab 37(6):1239–1246. doi:10.1139/h2012-115

    Article  CAS  PubMed  Google Scholar 

  37. Barnes CA, McNaughton BL (1980) Physiological compensation for loss of afferent synapses in rat hippocampal granule cells during senescence. J Physiol 299:473–485

    Article  Google Scholar 

  38. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  39. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  CAS  PubMed  Google Scholar 

  40. Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E et al (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 34(3):206–221. doi:10.1016/j.mrgentox.2009.01.007

    Article  Google Scholar 

  41. Collins A, Dusinska M, Franklin M, Somorovska M, Petrovska H, Duthie S, Fillion L, Panayiotidis M et al (1997) Comet assay in human biomonitoring studies: reliability, validation, and applications. Environ Mol Mutagen 29(2):139–146

    Article  Google Scholar 

  42. Deupree DL, Bradley J, Turner DA (1993) Age-related alterations in potentiation in the CA1 region in F334 rats. Neurobiol Aging 14:249–258

    Article  CAS  PubMed  Google Scholar 

  43. Moore CI, Browning MD, Rose GM (1993) Hippocampal plasticity induced by primed burst, but not long-term potentiation, stimulation is impaired in area CA1 of aged Fischer 334 rats. Hippocampus 3:57–66. doi:10.1002/hipo.450029106

    Article  CAS  PubMed  Google Scholar 

  44. Burger C (2010) Region-specific genetic alterations in the aging hippocampus: implications for cognitive aging. Front Aging Neurosci 2:140. doi:10.3289/fnagi.2010.00140

    Article  PubMed  PubMed Central  Google Scholar 

  45. Shih PC, Yang YR, Wang RY (2013) Effects of exercise intensity on spatial memory performance and hippocampal synaptic plasticity in transient brain ischemic rats. PLoS One 8(10):e78163. doi:10.1371/journal.pone.0078163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hescham S, Grace L, Kellaway LA, Bugarith K, Russell VA (2009) Effect of exercise on synaptophysin and calcium/calmodulin-dependent protein kinase levels in prefrontal cortex and hippocampus of a rat model of developmental stress. Metab Brain Dis 24(4):701–709. doi:10.1007/s11011-009-9165-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mizuno M, Yamada K, He J, Nakajima A, Nabeshima T (2003) Involvement of BDNF receptor TrkB in spatial memory formation. Learn Mem 10(2):108–115. doi:10.1101/lm.56003

    Article  PubMed  PubMed Central  Google Scholar 

  48. Yang JL, Lin YT, Chuang PC, Bohr VA, Mattson MP (2014) BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1. NeuroMolecular Med 16(1):161–174. doi:10.1007/s12017-013-8270-x

    Article  CAS  PubMed  Google Scholar 

  49. Hempstead BL (2002) The many faces of p75NTR. Curr Opin Neurobiol 12:260–267

    Article  CAS  PubMed  Google Scholar 

  50. Meeker RB, Williams KS (2015) The p75 neurotrophin receptor: at the crossroad of neural repair and death. Neural Regen Res 10(5):721–725. doi:10.4103/1673-5374.156967

    Article  PubMed  PubMed Central  Google Scholar 

  51. Ozbas-Gerceker F, Gorter JA, Redeker S, Ramkema M, van der Valk P, Baayen JC, Ozguc M, Saygi S et al (2004) Neurotrophin receptor immunoreactivity in the hippocampus of patients with mesial temporal lobe epilepsy. Neuropathol Appl Neurobiol 29:651–664. doi:10.1111/j.1355-2890.2004.00582.x

    Article  Google Scholar 

  52. Wei Y, Wang N, Lu Q, Zhang N, Zheng D, Li J (2007) Enhanced protein expressions of sortilin and p75NTR in retina of rat following elevated intraocular pressure-induced retinal ischemia. Neurosci Lett 428:169–174. doi:10.1016/j.neulet.2007.10.012

    Article  Google Scholar 

  53. Woo NH, Teng HK, Siao CJ, Chiaruttini C, Pang PT, Milner TA, Hempstead BL, Lu B (2005) Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci 8:1069–1077. doi:10.1038/nn1510

    Article  CAS  PubMed  Google Scholar 

  54. Sandoval M, Sandoval R, Thomas U, Spilker C, Smalla KH, Falcon R, Marengo JJ, Calderón R et al (2007) Antagonistic effects of TrkB and p75(NTR) on NMDA receptor currents in post-synaptic densities transplanted into Xenopus oocytes. J Neurochem 101(6):1672–1684. doi:10.1111/j.1471-4159.2007.04519.x

    Article  CAS  PubMed  Google Scholar 

  55. Benito E, Barco A (2010) CREB’s control of intrinsic and synaptic plasticity: implications for CREB-dependent memory models. Trends Neurosci 32:229–240. doi:10.1016/j.tins.2010.02.001

    Google Scholar 

  56. Lan JY, Skeberdis VA, Jover T, Grooms SY, Lin Y, Araneda RC, Zheng X, Bennett MV et al (2001) Protein kinase C modulates NMDA receptor trafficking and gating. Nat Neurosci 4(4):382–390. doi:10.1038/86028

    Article  CAS  PubMed  Google Scholar 

  57. Kleschevnikov AM, Routtenberg A (2001) PKC activation rescues LTP from NMDA receptor blockade. Hippocampus 11:168–175. doi:10.1002/hipo.1033

    Article  CAS  PubMed  Google Scholar 

  58. Perovic M, Tesic V, Mladenovic Djordjevic A, Smiljanic K, Loncarevic-Vasiljkovic N, Ruzdijic S, Kanazir S (2013) BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat. Age (Dordr) 34:2057–2070. doi:10.1007/s11347-012-9495-6

    Article  Google Scholar 

  59. Bonini JS, Cammarota M, Kerr DS, Bevilaqua LR, Izquierdo I (2005) Inhibition of PKC in basolateral amygdala and posterior parietal cortex impairs consolidation of inhibitory avoidance memory. Pharmacol Biochem Behav 80(1):63–67. doi:10.1016/j.pbb.2004.10.008

    Article  CAS  PubMed  Google Scholar 

  60. Guo Y, Feng P (2012) OX2R activation induces PKC-mediated ERK and CREB phosphorylation. Exp Cell Res 308(16):2004–2013. doi:10.1016/j.yexcr.2012.04.015

    Article  Google Scholar 

  61. Chennaoui M, Drogou C, Gomez-Merino D (2008) Effects of physical training on IL-1beta, IL-6 and IL-1ra concentrations in various brain areas of the rat. Eur Cytokine Netw 19:8–14. doi:10.1684/ecn.2008.0115

    CAS  PubMed  Google Scholar 

  62. Gomes da Silva S, Simões PSR, Mortara RA, Scorza FA, Cavalheiro EA, da Graça Naffah-Mazzacoratti M, Arida RM (2013) Exercise-induced hippocampal anti-inflammatory response in aged rats. J Neuroinflammation 10:10–61. doi:10.1186/1742-2094-10-61

    Article  Google Scholar 

  63. Tonelli LH, Postolache TT (2005) Tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and major histocompatibility complex molecules in the normal brain and after peripheral immune challenge. Neurol Res 27:679–684. doi:10.1179/016164105X49463

    Article  CAS  PubMed  Google Scholar 

  64. Khairova RA, Machado-Vieira R, Jing D, ManjiInt HK (2009) A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder. J Neuropsychopharmacol 12(4):561–578. doi:10.1017/S1461145709009924

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The present work was supported by grants from the Programa de Pós-Graduacão em Ciências da Saúde and Universidade do Extremo Sul Catarinense.

Author information

Authors and Affiliations

  1. Laboratory of Molecular and Cellular Biology Graduate Programme of Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, UNESC, 1105, Universitária Rd, Criciúma, SC, 88806000, Brazil

    Thais Ceresér Vilela, Adriani Paganini Damiani, Tamires Pavei Macan & Vanessa Moraes de Andrade

  2. Laboratory of Exercise Biochemistry and Physiology, Universidade do Extremo Sul Catarinense—UNESC, 1105, Universitária Rd, Criciúma, SC, 88806000, Brazil

    Alexandre Pastoris Muller, Sabrina da Silva, Paula Bortoluzzi Canteiro, Alisson de Sena Casagrande, Giulia dos Santos Pedroso, Renata Tiscoski Nesi & Ricardo Aurino de Pinho

Authors
  1. Thais Ceresér Vilela
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexandre Pastoris Muller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adriani Paganini Damiani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tamires Pavei Macan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sabrina da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paula Bortoluzzi Canteiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alisson de Sena Casagrande
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Giulia dos Santos Pedroso
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Renata Tiscoski Nesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vanessa Moraes de Andrade
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ricardo Aurino de Pinho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Alexandre Pastoris Muller or Vanessa Moraes de Andrade.

Ethics declarations

Ethics Statement

All experimental procedures were performed in accordance with the Brazilian Guidelines for the Care and Use of Animals for scientific and didactic purposes (DOU 27/5/13, MCTI), and the local ethics committee approved the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vilela, T.C., Muller, A.P., Damiani, A.P. et al. Strength and Aerobic Exercises Improve Spatial Memory in Aging Rats Through Stimulating Distinct Neuroplasticity Mechanisms. Mol Neurobiol 54, 7928–7937 (2017). https://doi.org/10.1007/s12035-016-0272-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-016-0272-x

Keywords

Search

Navigation