Abstract
N-methyl-d-aspartate receptor (NR) is involved in activity-dependent synaptic plasticity, such as associative long-term potentiation, and in related central functions, such as learning and memory. In this study, we observed effects of treadmill exercise on NR1 and doublecortin (DCX, a marker for neuroblast differentiation) in the subgranular zone of the dentate gyrus (DG). At 6 weeks of age, rats were put on a treadmill with or without running for 1 h/day for 5 consecutive days at 22 m/min for 5 weeks. Exercise increased NR1 immunoreactivity and protein level in the hippocampus. To identify the correlations between NR and neuroblasts, we intraperitoneally administered a NR antagonist, MK-801, to the exercised rats. MK-801 treatment reduced NR1 protein level in the hippocampus of the exercised rats. In addition, in the MK-801-treated group, the number of DCX cells was significantly decreased in the subgranular zone of the DG. These results suggest that NR may be one of the important factors that modulate neuroblast differentiation during exercise in rats.
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Arvidsson A, Kokaia Z, Lindvall O (2001) N-methyl-d-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke. Eur J Neurosci 14(1):10–18
Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361(6407):31–39
Butler AK, Uryu K, Chesselet MF (1998) A role for N-methyl-d-aspartate receptors in the regulation of synaptogenesis and expression of the polysialylated form of the neural cell adhesion molecule in the developing striatum. Dev Neurosci 20(2–3):253–262
Cameron HA, McEwen BS, Gould E (1995) Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus. J Neurosci 15(6):4687–4692
Christie BR, Swann SE, Fox CJ, Froc D, Lieblich SE, Redila V, Webber A (2005) Voluntary exercise rescues deficits in spatial memory and long-term potentiation in prenatal ethanol-exposed male rats. Eur J Neurosci 21(6):1719–1726
Ciani E, Rizzi S, Paulsen RE, Contestabile A (1997) Chronic pre-explant blockade of the NMDA receptor affects survival of cerebellar granule cells explanted in vitro. Brain Res Dev Brain Res 99(1):112–117
Deslandes A, Moraes H, Ferreira C, Veiga H, Silveira H, Mouta R, Pompeu FA, Coutinho ES, Laks J (2009) Exercise and mental health: many reasons to move. Neuropsychobiology 59(4):191–198
Devine JM, Zafonte RD (2009) Physical exercise and cognitive recovery in acquired brain injury: a review of the literature. PM R 1(6):560–575
Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH, Christie BR (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(1):71–79
Francis F, Koulakoff A, Boucher D, Chafey P, Schaar B, Vinet MC, Friocourt G, McDonnell N, Reiner O, Kahn A, McConnell SK, Berwald-Netter Y, Denoulet P, Chelly J (1999) Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 23(2):247–256
Garcez RC, Teixeira BL, Schmitt Sdos S, Alvarez-Silva M, Trentin AG (2009) Epidermal growth factor (EGF) promotes the in vitro differentiation of neural crest cells to neurons and melanocytes. Cell Mol Neurobiol 29(8):1087–1091
Ghiani CA, Beltran-Parrazal L, Sforza DM, Malvar JS, Seksenyan A, Cole R, Smith DJ, Charles A, Ferchmin PA, de Vellis J (2007) Genetic program of neuronal differentiation and growth induced by specific activation of NMDA receptors. Neurochem Res 32(2):363–376
Gleeson JG, Lin PT, Flanagan LA, Walsh CA (1999) Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 23(2):257–271
Gottlieb M, Matute C (1997) Expression of ionotropic glutamate receptor subunits in glial cells of the hippocampal CA1 area following transient forebrain ischemia. J Cereb Blood Flow Metab 17(3):290–300
Gould E, McEwen BS, Tanapat P, Galea LA, Fuchs E (1997) Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci 17(7):2492–2498
Huerta PT, Sun LD, Wilson MA, Tonegawa S (2000) Formation of temporal memory requires NMDA receptors within CA1 pyramidal neurons. Neuron 25(2):473–480
Hwang IK, Yi SS, Yoo KY, Park OK, Yan B, Kim IY, Kim YN, Song W, Moon SM, Won MH, Seong JK, Yoon YS (2010) Effects of treadmill exercise on cyclooxygenase-2 in the hippocampus in type 2 diabetic rats: correlation with the neuroblasts. Brain Res 1341:84–92
Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K, Tenkova TI, Stefovska V, Turski L, Olney JW (1999) Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 283(5398):70–74
Ikonomidou C, Stefovska V, Turski L (2000) Neuronal death enhanced by N-methyl-d-aspartate antagonists. Proc Natl Acad Sci USA 97(23):12885–12890
Jaako-Movits K, Zharkovsky A (2005) Impaired fear memory and decreased hippocampal neurogenesis following olfactory bulbectomy in rats. Eur J Neurosci 22(11):2871–2878
Joo JY, Kim BW, Lee JS, Park JY, Kim S, Yun YJ, Lee SH, Rhim H, Son H (2007) Activation of NMDA receptors increases proliferation and differentiation of hippocampal neural progenitor cells. J Cell Sci 120(Pt 8):1358–1370
Kee N, Teixeira CM, Wang AH, Frankland PW (2007) Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat Neurosci 10(3):355–362
Kempermann G, Kuhn HG, Gage FH (1997) Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc Natl Acad Sci USA 94(19):10409–10414
Kitamura T, Mishina M, Sugiyama H (2003) Enhancement of neurogenesis by running wheel exercises is suppressed in mice lacking NMDA receptor epsilon 1 subunit. Neurosci Res 47(1):55–63
Kluska MM, Witte OW, Bolz J, Redecker C (2005) Neurogenesis in the adult dentate gyrus after cortical infarcts: effects of infarct location, N-methyl-d-aspartate receptor blockade and anti-inflammatory treatment. Neuroscience 135(3):723–735
Kong X, Li X, Cai Z, Yang N, Liu Y, Shu J, Pan L, Zuo P (2008) Melatonin regulates the viability and differentiation of rat midbrain neural stem cells. Cell Mol Neurobiol 28(4):569–579
Laplagne DA, Kamienkowski JE, Espósito MS, Piatti VC, Zhao C, Gage FH, Schinder AF (2007) Similar GABAergic inputs in dentate granule cells born during embryonic and adult neurogenesis. Eur J Neurosci 25(10):2973–2981
Lou SJ, Liu JY, Chang H, Chen PJ (2008) Hippocampal neurogenesis and gene expression depend on exercise intensity in juvenile rats. Brain Res 1210:48–55
Maeda K, Sugino H, Hirose T, Kitagawa H, Nagai T, Mizoguchi H, Takuma K, Yamada K (2007) Clozapine prevents a decrease in neurogenesis in mice repeatedly treated with phencyclidine. J Pharmacol Sci 103(3):299–308
McHugh TJ, Jones MW, Quinn JJ, Balthasar N, Coppari R, Elmquist JK, Lowell BB, Fanselow MS, Wilson MA, Tonegawa S (2007) Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science 317(5834):94–99
Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12(3):529–540
Nacher J, McEwen BS (2006) The role of N-methyl-d-aspartate receptors in neurogenesis. Hippocampus 16(3):267–270
Nácher J, Varea E, Miguel Blasco-Ibáñez J, Gómez-Climent MA, Castillo-Gómez E, Crespo C, Martínez-Guijarro FJ, McEwen BS (2007) N-methyl-d-aspartate receptor expression during adult neurogenesis in the rat dentate gyrus. Neuroscience 144(3):855–864
Nakazawa K, Quirk MC, Chitwood RA, Watanabe M, Yeckel MF, Sun LD, Kato A, Carr CA, Johnston D, Wilson MA, Tonegawa S (2002) Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science 297(5579):211–218
Orendácová J, Raceková E, Orendác M, Martoncíková M, Saganová K, Lievajová K, Abdiová H, Labun J, Gálik J (2009) Immunohistochemical study of postnatal neurogenesis after whole-body exposure to electromagnetic fields: evaluation of age- and dose-related changes in rats. Cell Mol Neurobiol 29(6–7):981–990
Paizanis E, Kelaï S, Renoir T, Hamon M, Lanfumey L (2007) Life-long hippocampal neurogenesis: environmental, pharmacological and neurochemical modulations. Neurochem Res 32(10):1762–1771
Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates, 5th edn. Elsevier Academic Press, Boston, Amsterdam
Picard-Riera N, Nait-Oumesmar B, Baron-Van Evercooren A (2004) Endogenous adult neural stem cells: limits and potential to repair the injured central nervous system. J Neurosci Res 76(2):223–231
Ramirez-Amaya V, Marrone DF, Gage FH, Worley PF, Barnes CA (2006) Integration of new neurons into functional neural networks. J Neurosci 26(47):12237–12241
Rampon C, Tang YP, Goodhouse J, Shimizu E, Kyin M, Tsien JZ (2000) Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice. Nat Neurosci 3(3):238–244
van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2(3):266–270
Veena J, Srikumar BN, Raju TR, Shankaranarayana Rao BS (2009) Exposure to enriched environment restores the survival and differentiation of new born cells in the hippocampus and ameliorates depressive symptoms in chronically stressed rats. Neurosci Lett 455(3):178–182
Watanabe M, Fukaya M, Sakimura K, Manabe T, Mishina M, Inoue Y (1998) Selective scarcity of NMDA receptor channel subunits in the stratum lucidum (mossy fibre-recipient layer) of the mouse hippocampal CA3 subfield. Eur J Neurosci 10(2):478–487
Xi D, Zhang W, Wang HX, Stradtman GG, Gao WJ (2009) Dizocilpine (MK-801) induces distinct changes of N-methyl-d-aspartic acid receptor subunits in parvalbumin-containing interneurons in young adult rat prefrontal cortex. Int J Neuropsychopharmacol 12(10):1395–1408
Yi SS, Hwang IK, Yoo KY, Park OK, Yu J, Yan B, Kim IY, Kim YN, Pai T, Song W, Lee IS, Won MH, Seong JK, Yoon YS (2009) Effects of treadmill exercise on cell proliferation and differentiation in the subgranular zone of the dentate gyrus in a rat model of type II diabetes. Neurochem Res 34(6):1039–1046
Acknowledgments
The authors would like to thank Mr. Seok Han, Mr. Seung Uk Lee, and Ms. Hyun Sook Kim for their technical help in this study. This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0010580), and by a grant (2010K000823) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology, the Republic of Korea.
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Jung Hoon Choi and Ki-Yeon Yoo contributed equally to this article.
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Choi, J.H., Yoo, KY., Lee, C.H. et al. Effects of Treadmill Exercise Combined with MK 801 Treatment on Neuroblast Differentiation in the Dentate Gyrus in Rats. Cell Mol Neurobiol 31, 285–292 (2011). https://doi.org/10.1007/s10571-010-9619-4
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DOI: https://doi.org/10.1007/s10571-010-9619-4