Document Type : Original Article

Authors

1 Professor of Physiology, Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Assistant Professor of Physiology, Animal Sciences Group, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

3 MSc in Animal Physiology, Animal Sciences Group, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

Abstract

Reelin is an extracellular matrix neuroprotein which plays important roles during development and maturation of cerebellum. In the postnatal cerebellum, Reelin is synthesized by cerebellar granule cells and secreted to extracellular matrix. This secreted protein modulates adult synaptic function, neurotransmitter release and regulates plasticity. Exercise has beneficial effects on central nervous system. This study investigated the effects of short and long-term training program on Reelin protein levels in the cerebellum. Forty male rats divided into four main groups; test 1 (15 days exercise-trained rats) and test 2 (60 days exercise-trained rats), and control 1 (rats were kept alive for 15 days) and control 2 (rats were kept alive for 60 days). At the end of the training period, Reelin levels in the cerebellum were measured by ELISA assay. Results showed that short and long-term regular exercise had no effect on Reelin protein levels in the cerebellum. Present study showed that regular exercise could not change Reelin protein concentration which mediated plasticity, dendritogenesis and synaptogenesis in the cerebellar neurons. Results of this study could correlate with unaffected plasticity, dendritogenesis and synaptogenesis in the cerebellum under exercise conditions as reported in previous studies.

Keywords

Alcántara, S., Ruiz, M., D’Arcangelo, G., Ezan, F., de Lecea, L., Curran, T., Sotelo, C., and Soriano, E. (1998). Regional and cellular patterns of reelin mRNA expression in the forebrain of the developing and adult mouse. The Journal of Neuroscience, 18(19):7779-7799.
Anderson, B.J., Alcantara, A.A., and Greenough, W.T. (1996). Motor-skill learning: changes in synaptic organization of the rat cerebellar cortex. Neurobiology of learning and memory, 66(2):221-229.
Ayoub R. (2009). Effect of exercise on spatial learning and memory in male diabetic rats. Int J Diabetes & Metabolism, 17:93-98.
Bauer PM, Hanson JL, Pierson RK, Davidson RJ, and Pollak SD. (2009). Cerebellar volume and cognitive functioning in children who experienced early deprivation. Biological psychiatry, 66(12):1100-1106.
Beffert, U., Weeber, E.J., Durudas, A., Qiu, S., Masiulis, I., Sweatt, J.D., Li, W-P., Adelmann, G., Frotscher, M., and Hammer, R.E. (2005). Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2. Neuron, 47(4):567-579.
Black, J.E., Isaacs, K.R., Anderson, B.J., Alcantara, A.A., and Greenough, W.T. (1990). Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proceedings of the National Academy of Sciences, 87(14):5568-5572.
Borrell, Vc., Del Rı́o, J.A, Alcántara, S., Derer, M., Martı́nez, A., D’Arcangelo, G., Nakajima, K., Mikoshiba, K., Derer, P., and Curran, T. (1999). Reelin regulates the development and synaptogenesis of the layer-specific entorhino-hippocampal connections. The Journal of Neuroscience, 19(4):1345-1358.
Burghardt, P.R., Fulk, L.J., Hand, G.A., and Wilson, M.A. (2004). The effects of chronic treadmill and wheel running on behavior in rats. Brain research, 1019(1):84-96.
Chen, Y., Beffert, U., Ertunc, M., Tang, T-S., Kavalali, E.T., Bezprozvanny, I., and Herz, J. (2005). Reelin modulates NMDA receptor activity in cortical neurons. The Journal of Neuroscience, 25(36):8209-8216.
D'Arcangelo, G., Homayouni, R., Keshvara, L., Rice, D.S., Sheldon, M., and Curran, T. (1999). Reelin is a ligand for lipoprotein receptors. Neuron, 24(2):471-479.
D’Arcangelo, G., Nakajima, K., Miyata, T., Ogawa, M., Mikoshiba, K and Curran, T. (1997). Reelin is a secreted glycoprotein recognized by the CR-50 monoclonal antibody. The Journal of Neuroscience, 17(1):23-31.
De Bergeyck, V., Nakajima, K., de Rouvroit, C.L., Naerhuyzen, B., Goffinet, A., Miyata, T., Ogawa, M and Mikoshiba, K. (1997). A truncated Reelin protein is produced but not secreted in the ‘Orleans’ reeler mutation (Reln[rl-Orl]). Molecular brain research, 50(1):85-90.
Del Río, J.A., Heimrich, B., Borrell, V., Förster, E., Drakew, A., Alcántara, S., Nakajima, K., Miyata, T., Ogawa, M and Mikoshiba, K. (1997). A role for Cajal–Retzius cells and reelin in the development of hippocampal connections. Nature, 385:70-74.
Fatemi, S.H. 2004. Reelin glycoprotein: structure, biology and roles in health and disease. Molecular psychiatry, 10(3):251-257.
Fine, E.J., Ionita, C.C and Lohr, L. (2002). The history of the development of the cerebellar examination. Seminars in neurology, p 375-384.
Giompres, P., and Delis, F. 2005. Dopamine transporters in the cerebellum of mutant mice. The Cerebellum, 4(2):105-111.
Hellwig, S., Hack, I., Kowalski, J., Brunne, B., Jarowyj, J., Unger, A., Bock, H.H., Junghans, D and Frotscher, M. (2011). Role for Reelin in neurotransmitter release. The Journal of Neuroscience, 31(7):2352-2360.
Hesari, F.S and Sales E.K. (2013). Reelin and Regular Exercise in the Brain Cortex of Healthy Adult Rats. Journal of Animal Science Advances, 3(11):569-574.
Hiesberger, T., Trommsdorff, M., Howell, B.W., Goffinet, A., Mumby, M.C., Cooper, J.A and Herz, J. (1999). Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation. Neuron, 24(2):481-489.
Huang, C-C and D’Arcangelo, G. (2008). The Reelin Gene and Its Functions in Brain Development. In: Fatemi SH, editor. Reelin Glycoprotein Structure, Biology and Roles in Health and Disease. Springer.
Kandel, E.R., Schwartz, J.H and Jessell, T.M. (2000). Principles of neural science: McGraw-Hill New York.
Kennard, J.A and Woodruff-Pak, D.S. (2012). A comparison of low-and high-impact forced exercise: Effects of training paradigm on learning and memory. Physiology & behavior, 106(4):423-427.
Kleim, J.A., Cooper, N.R and VandenBerg, P.M. (2002). Exercise induces angiogenesis but does not alter movement representations within rat motor cortex. Brain research 934(1):1-6.
Kleim, J.A., Markham, J.A., Vij, K., Freese, JL., Ballard, D.H., and Greenough, W.T. 2007. Motor learning induces astrocytic hypertrophy in the cerebellar cortex. Behavioural brain research, 178(2):244-249.
Leasure, J and Jones, M. (2008). Forced and voluntary exercise differentially affect brain and behavior. Neuroscience, 156(3):456-465.
Maloku, E., Covelo, I.R., Hanbauer, I., Guidotti, A., Kadriu, B., Hu, Q., Davis, J.M and Costa, E. (2010). Lower number of cerebellar Purkinje neurons in psychosis is associated with reduced reelin expression. Proceedings of the National Academy of Sciences, 107(9):4407-4411.
Molteni, R., Ying, Z and Gómez‐Pinilla, F. (2002). Differential effects of acute and chronic exercise on plasticity‐related genes in the rat hippocampus revealed by microarray. European Journal of Neuroscience, 16(6):1107-1116.
Niu, S., Renfro, A., Quattrocchi, C.C., Sheldon, M and D'Arcangelo, G. (2004). Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway. Neuron, 41(1):71-84.
Niu, S., Yabut, O and D'Arcangelo, G. (2008). The Reelin signaling pathway promotes dendritic spine development in hippocampal neurons. The Journal of Neuroscience, 28(41):10339-10348.
Rice, D.S., and Curran, T. (2001). Role of the reelin signaling pathway in central nervous system development. Annual review of neuroscience, 24(1):1005-1039.
Tissir, F and Goffinet, A.M. 2003. Reelin and brain development. Nature Reviews Neuroscience, 4(6):496-505.
Van Praag, H., Shubert, T., Zhao, C and Gage, F.H. (2005). Exercise enhances learning and hippocampal neurogenesis in aged mice. The Journal of Neuroscience, 25(38):8680-8685.
Weeber, E.J., Beffert, U., Jones, C., Christian, J.M., Förster, E., Sweatt, J.D and Herz, J. (2002). Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning. Journal of Biological Chemistry, 277(42):39944-39952.
Zhao, C., Teng, E.M., Summers, R.G., Ming, G-l and Gage, F.H. (2006). Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. The Journal of Neuroscience, 26(1):3-11.