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01-01-2014 | Original Article

Physical exercise increases GFAP expression and induces morphological changes in hippocampal astrocytes

Authors: Lisiani Saur, Pedro Porto Alegre Baptista, Priscylla Nunes de Senna, Mariana Fontoura Paim, Patricia do Nascimento, Jocemar Ilha, Pamela Brambilla Bagatini, Matilde Achaval, Léder Leal Xavier

Published in: Brain Structure and Function | Issue 1/2014

Abstract

Physical exercise has an important influence on brain plasticity, which affects the neuron–glia interaction. Astrocytes are susceptible to plasticity, and induce and stabilize synapses, regulate the concentration of various molecules, and support neuronal energy metabolism. The aim of our study was to investigate whether physical exercise is capable of altering the morphology, density and expression of glial fibrillary acidic protein (GFAP) in astrocytes from the CA1 region of rat hippocampus. Thirteen male rats were divided in two groups: sedentary (n = 6) and exercise (n = 7). The animals in the exercise group were submitted to a protocol of daily physical exercise on a treadmill for four consecutive weeks. GFAP immunoreactivity was evaluated using optical densitometry and the morphological analyses were an adaptation of Sholl’s concentric circles method. Our results show that physical exercise is capable of increasing the density of GFAP-positive astrocytes as well as the regional and cellular GFAP expression. In addition, physical exercise altered astrocytic morphology as shown by the increase observed in the degree of ramification in the lateral quadrants and in the length of the longest astrocytic processes in the central quadrants. Our data demonstrate important changes in astrocytes promoted by physical exercise, supporting the idea that these cells are involved in regulating neural activity and plasticity.

Alaei H, Moloudi R, Sarkaki AR (2008) Effects of treadmill running on mid-term memory and swim speed in the rat with Morris water maze test. J Bodyw Mov Ther 12:72–75PubMedCrossRef

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

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2008) Molecular biology of the cell, 5th edn. Garland Science, New York

Allen NJ, Barres BA (2005) Signaling between glia and neurons: focus on synaptic plasticity. Curr Opin Neurobiol 15:542–548PubMedCrossRef

Andersen P, Morris R, Amaral D, Bliss T, O’Keefe J (2007) The hippocampus book. Oxford University Press, New York

Berchtold NC, Castello N, Cotman CW (2010) Exercise and time-dependent benefits to learning and memory. Neuroscience 167:588–597PubMedCentralPubMedCrossRef

Björklund H, Dahl D, Haglid K, Rosengren L, Olson L (1983) Astrocytic development in fetal parietal cortex grafted to cerebral and cerebellar cortex of immature rats. Dev Brain Res 9:171–180CrossRef

Buckman LB, Thompson MM, Moreno HN, Ellacott KLJ (2012) Regional astrogliosis in the mouse hypothalamus in response to obesity. J Comp Neurol. doi:10.1002/cne.23233

Bushong EA, Martone ME, Jones YZ, Ellisman MH (2002) Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci 22:183–192PubMed

Canady KS, Ali-Osman F, Rubel EW (1990) Extracellular potassium influences DNA and protein syntheses and glial fibrillary acidic protein expression in cultured glial cells. Glia 3(5):368–374PubMedCrossRef

Catalani A, Sabbatini M, Consoli C, Cinque C, Tomassoni D, Azmitia E, Angelucci L, Amenta F (2002) Glial fibrillary acidic protein immunoreactive astrocytes in developing rat hippocampus. Mech Ageing Dev 123:481–490PubMedCrossRef

Chen WJ, Liem RK (1994) Reexpression of glial fibrillary acidic protein rescues the ability of astrocytoma cells to form processes in response to neurons. J Cell Biol 127:813–823PubMedCrossRef

Coleman E, Judd R, Hoe L, Dennis J, Posner P (2004) Effects of diabetes mellitus on astrocyte GFAP and glutamate transporters in the CNS. Glia 48:166–178PubMedCrossRef

Dahl D, Rueger DC, Bignami A, Weber K, Osborn M (1981) Vimentin, the 57,000 molecular weight protein of fibroblast filaments, is the major cytoskeletal component in immature glia. Eur J Cell Biol 24(2):191–196PubMed

Dall’Oglio A, Gehlen G, Achaval M, Rasia-Filho AA (2008) Dendritic branching features of Golgi-impregnated neurons from the “ventral” medial amygdala subnuclei of adult male and female rats. Neurosci Lett 439:287–292PubMedCrossRef

de Senna PN, Ilha J, Baptista PP, do Nascimento PS, Leite MC, Paim MF, Gonçalves CA, Achaval M, Xavier LL (2011) Effects of physical exercise on spatial memory and astroglial alterations in the hippocampus of diabetic rats. Metab Brain Dis 26:269–279PubMedCrossRef

Derouiche A, Pannicke T, Haseleu J, Blaess S, Grosche J, Reichenbach A (2012) Beyond polarity: functional membrane domains in astrocytes and müller cells. Neurochem Res 37:2513–2523PubMedCrossRef

Dietrich MO, Andrews ZB, Horvath TL (2008) Exercise-induced synaptogenesis in the hippocampus is dependent on UCP2-regulated mitochondrial adaptation. J Neurosci 28:10766–10771PubMedCrossRef

Dutra MF, Jaeger M, Ilha J, Kalil-Gaspar PI, Marcuzzo S, Achaval M (2012) Exercise improves motor deficits and alters striatal GFAP expression in a 6-OHDA-induced rat model of Parkinson’s disease. Neurol Sci 33:1137–1144PubMedCrossRef

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 486:39–47PubMedCrossRef

Eddleston M, Mucke L (1993) Molecular profile of reactive astrocytes-implications for their role in neurologic disease. Neuroscience 54:15–36PubMedCrossRef

Farmer J, Zhao X, Van Praag H, Wodtke K, Gage FH, Chistie 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 124:71–79PubMedCrossRef

Ferraz AC, Xavier LL, Hernandes S, Sulzbach M, Viola GG, Anselmo-Franci JA, Achaval M, Da Cunha C (2003) Failure of estrogen to protect the substantia nigra pars compacta of female rats from lesion induced by 6-hydroxydopamine. Brain Res 986:200–205PubMedCrossRef

Ferreira AF, Real CC, Rodrigues AC, Alves AS, Britto LR (2011) Short-term, moderate exercise is capable of inducing structural, BDNF-independent hippocampal plasticity. Brain Res 1425:111–122PubMedCrossRef

Freund TF, Buzsáki G (1996) Interneurons of the Hippocampus. Hippocampus 6:347–470PubMedCrossRef

Gómez-Pinilla F, Vu L, Cotman CW (1995) Regulation of astrocyte proliferation by FGF-2 and heparan sulfate in vivo. J Neurosci 15:2021–2029PubMed

Gómez-Pinilla F, Dao L, So V (1997) Physical exercise induces FGF-2 and its mRNA in the hippocampus. Brain Res 764:1–8PubMedCrossRef

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 85:53–61PubMedCrossRef

Haber M, Zhou L, Murai KK (2006) Cooperative astrocyte and dendritic spine dynamics at hippocampal excitatory synapses. J Neurosci 26:8881–8891PubMedCrossRef

Hashem HE, Safwat MDED, Algaidi S (2012) The effect of monosodium glutamate on the cerebellar cortex of male albino rats and the protective role of vitamin C (histological and immunohistochemical study). J Mol Hist 43:179–186CrossRef

Hillman CH, Erickson KI, Kramer AF (2008) Be smart, exercise your heart: exercise effects on brain and cognition. Nature Rev 9:58–65CrossRef

Jones TA, Hawrylak N, Greenough WT (1996) Rapid laminar-dependent changes in GFAP immunoreactive astrocytes in the visual cortex of rats reared in a complex environment. Psychoneuroendocrinology 21:189–201PubMedCrossRef

Kashihara K, Maruyama T, Murota M, Nakahara Y (2009) Positive effects of acute and moderate physical exercise on cognitive function. J Physiol Anthropol 28(4):155–164PubMedCrossRef

Kim HB, Jang MH, Shin MC, Lim BV, Kim YP, Kim KJ, Kim EH, Kim CJ (2003) Treadmill exercise increases cell proliferation in dentate gyrus of rats with streptozotocin-induced diabetes. J Diabetes Complicat 17:29–33PubMedCrossRef

Komitova M, Zhao LR, Gidö G, Johansson BB, Eriksson P (2005) Postischemic exercise attenuates whereas enriched environment has certain enhancing effects on lesion-induced subventricular zone activation in the adult rat. Eur J Neurosci 21:2397–2405PubMedCrossRef

Kraig RP, Dong L, Thisted R, Jaegep CB (1991) Spreading depression increases immunohistochemical staining of glial fibrillary acidic protein. J Neurosci 17(7):2187–2199

Kramer AF, Erickson KI, Colcombe SJ (2006) Exercise, cognition, and the aging brain. J Appl Physiol 101:1237–1242PubMedCrossRef

Laurin D, Verreault R, Lindsay J, MacPherson K, Rockwood K (2001) Physical activity and risk of cognitive impairment and dementia in elderly person. Arch Neurol 58:498–504PubMedCrossRef

Lewis GP, Erickson PA, Guérin CJ, Anderson DH, Fisher SK (1992) Basic fibroblast growth factor: a potential regulator of proliferation and intermediate filament expression in the retina. J Neurosci 12:3968–3978PubMed

Li J, Ding YH, Rafols JA, Lai Q, McAllister JP 2nd, Ding Y (2005) Increased astrocyte proliferation in rats after running exercise. Neurosci Lett 386:160–164PubMedCrossRef

Lin TW, Chen SJ, Huang TY, Chang CY, Chuang JI, Wu FS, Kuo YM, Jen CJ (2012) Different types of exercise induce differential effects on neuronal adaptations and memory performance. Neurobiol Learn Mem 97:140–147PubMedCrossRef

Martinez FG, Hermel EE, Xavier LL, Viola GG, Riboldi J, Rasia-Filho AA, Achaval M (2006) Gonadal hormone regulation of glial fibrillary acidic protein immunoreactivity in the medial amygdala subnuclei across the estrous cycle and in castrated and treated female rats. Brain Res 1108:117–126PubMedCrossRef

Martinsen EW (2008) Physical activity in the prevention and treatment of anxiety and depression. Nord J Psychiatry 47:25–29CrossRef

Matsutani S, Leon M (1993) Elaboration of glial cell processes in the rat olfactory bulb associated with early learning. Brain Res 613:317–320PubMedCrossRef

McCall MA, Gregg RG, Behringer RR, Brenner M, Delaney CL, Galbreath EJ, Zhang CL, Pearce RA, Chiu SY, Messing A (1996) Targeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology. Proc Natl Acad Sci 93:6361–6366PubMedCrossRef

Mestriner RG, Pagnussat AS, Boisserand LSB, Valentim L, Netto CA (2011) Skilled reaching training promotes astroglial changes and facilitated sensorimotor recovery after collagenase-induced intracerebral hemorrhage. Exp Neurol 227:53–61PubMedCrossRef

Mirochnic S, Wolf S, Staufenbiel M, Kempermann G (2009) Age effects on the regulation of adult hippocampal neurogenesis by physical activity and environmental enrichment in the APP23 mouse model of Alzheimer disease. Hippocampus 19:1008–1018PubMedCrossRef

Neeper SA, Gómez-Pinilla F, Choi J, Cotman CW (1996) Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res 726:49–56PubMedCrossRef

Nithianantharajah J, Hannan AJ (2006) Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci 7:697–709PubMedCrossRef

Nixdorf-Bergweiler BE, Albrecht B, Heinemann U (1994) Developmental changes in the number, size, and orientation of GFAP-positive cells in the CA1 region of rat hippocampus. Glia 12:180–195PubMedCrossRef

Ohira K, Funatsu N, Homma KJ, Sahara Y, Hayashi M, Kaneko T, Nakamura S (2007) Truncated TrkB-T1 regulates the morphology of neocortical layer I astrocytes in adult rat brain slices. Eur J Neurosci 25:406–416PubMedCrossRef

Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press, San Diego

Penfold PL, Prods JM, Madigan MC, van Driel D, Billson FA (1990) Angiogenesis in normal human retinal development: the involvement of astrocytes and macrophages. Graefes Arch Clin Exp Ophthalmol 228:255–263PubMedCrossRef

Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32:421–443PubMedCrossRef

Pixley SKR, Vellis J (1984) Transition between immature radial glia and mature astrocytes studied with a monoclonal antibody to vimentin. Dev Brain Res 15:201–2091984CrossRef

Rodnight R, Gonçalves CA, Wofchuk ST, Leal R (1997) Control of the phosphorylation of the astrocyte marker glial fibrillary acidic protein (GFAP) in the immature rat hippocampus by glutamate and calcium ions: possible key factor in astrocytic plasticity. Braz J Med Biol Res 30:325–338PubMedCrossRef

Rodrigues L, Dutra MF, Ilha J, Biasibetti R, Quincozes-Santos A, Leite MC, Marcuzzo S, Achaval M, Gonçalves CA (2010) Treadmill training restores spatial cognitive deficits and neurochemical alterations in the hippocampus of rats submitted to an intracerebroventricular administration of streptozotocin. J Neural Transm 117:1295–1305PubMedCrossRef

Schäfer S, Calas AG, Vergouts M, Hermans E (2012) Immunomodulatory influence of bone marrow-derived mesenchymal stem cells on neuroinflammation in astrocyte cultures. J Neuroimmunol 249:40–48PubMedCrossRef

Shibuki K, Gomi H, Chen L, Bao S, Kim JJ, Wakatsuki H, Fujisaki T, Fujimoto K, Katoh A, Ikeda T, Chen C, Thompson RF, Itohara S (1996) Deficient cerebellar long-term depression, impaired eyeblink conditioning, and normal motor coordination in GFAP mutant mice. Neuron 16:587–599PubMedCrossRef

Sholl DA (1953) Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 87:387–406PubMed

Sirevaag AM, Greenough WT (1991) Plasticity of GFAP-immunoreactive astrocyte size and number in visual cortex of rats reared in complex environments. Brain Res 540:273–278PubMedCrossRef

Smith AD, Zigmond MJ (2003) Can the brain be protected through exercise? Lessons from an animal model of parkinsonism. Exp Neurol 184:31–39PubMedCrossRef

Squire LR, Stark CE, Clark RE (2004) The medial temporal lobe. Annu Rev Neurosci 27:279–306PubMedCrossRef

Steward O, Torre ER, Tomasulo R, Lothman E (1991) Neuronal activity up-regulates astroglial gene expression. Proc Natl Acad Sci 88:6819–6823PubMedCrossRef

Steward O, Kelley MS, Schauwecker PE (1997) Signals that regulate astroglial gene expression: induction of GFAP mRNA following seizures or injury is blocked by protein synthesis inhibitors. Exp Neurol 148:100–109PubMedCrossRef

Stranahan AM, Lee K, Becker KG, Zhang Y, Maudsley S, Martin B, Cutler RG, Mattson MP (2010) Hippocampal gene expression patterns underlying the enhancement of memory by running in aged mice. Neurobiol Aging 31:1937–1949PubMedCentralPubMedCrossRef

Stummer W, Weber K, Tranmer B, Baethmann A, Kempski O (1994) Reduced mortality and brain damage after locomotor activity in gerbil forebrain ischemia. Stroke 25:1862–1869PubMedCrossRef

Suárez I, Bodega G, Rubio M, Garcia-Segura LM, Fernádez B (1994) Astroglial induction of in vivo angiogenesis. J Neural Transplant Plast 5:1–10PubMedCentralPubMed

Tansey FA, Farooq M, Cammer W (1991) Glutamine synthetase in oligodendrocytes and astrocytes: new biochemical and immunocytochemical evidence. J Neurochem 56(1):266–272PubMedCrossRef

Theodosis DT, Poulain DA, Oliet SH (2008) Activity-dependent structural and functional plasticity of astrocyte-neuron interactions. Physiol Rev 88:983–1008PubMedCrossRef

Uda M, Ishido M, Kami K, Masuhara M (2006) Effects of chronic treadmill running on neurogenesis in the dentate gyrus of the hippocampus of adult rat. Brain Res 1104:64–72PubMedCrossRef

van der Borght K, Kóbor-Nyakas DE, Klauke K, Eggen BJ, Nyakas C, van der Zee EA, Meerlo P (2009) Physical exercise leads to rapid adaptations in hippocampal vasculature: temporal dynamics and relationship to cell proliferation and neurogenesis. Hippocampus 19:928–936PubMedCrossRef

van Praag H, Christie BR, Sejnowski TJ, Gage FH (1999a) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci 96:13427–13431PubMedCrossRef

van Praag H, Kempermann G, Gage FH (1999b) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266–270PubMedCrossRef

van Praag H, Shubert T, Zhao C, Gage FH (2005) Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25:8680–8685PubMedCentralPubMedCrossRef

Verkhratsky A, Butt A (2007) Glial Neurobiology. Wiley, EnglandCrossRef

Viola GG, Rodrigues L, Américo JC, Hansel G, Vargas RS, Biasibetti R, Swarowsky A, Gonçalves CA, Xavier LL, Achaval M, Souza DO, Amaral OB (2009) Morphological changes in hippocampal astrocytes induced by environmental enrichment in mice. Brain Res 1274:47–54PubMedCrossRef

Weinstein DE, Shelanski ML, Liem RK (1991) Suppression by antisense mRNA demonstrates a requirement for the glial fibrillary acidic protein in the formation of stable astrocytic processes in response to neurons. J Cell Biol 112:1205–1213PubMedCrossRef

Wenzel J, Lammert G, Meyer U, Krug M (1991) The influence of long-term potentiation on the spatial relationship between astrocyte processes and potentiated synapses in the dentate gyrus neuropil of rat brain. Brain Res 560:122–131PubMedCrossRef

Williams MR, Hampton T, Pearce RKB, Hirsch SR, Ansorge O, Thom M, Maier M (2012) Astrocyte decrease in the subgenual cingulate and callosal genu in schizophrenia. Eur Arch Psychiatry Clin Neurosci. doi:10.1007/s00406-012-0328-5

Wu Y, Zhang AQ, Yewa DT (2005) Age related changes of various markers of astrocytes in senescence-accelerated mice hippocampus. Neurochem Int 46:565–574PubMedCrossRef

Xavier LL, Viola GG, Ferraz AC, Da Cunha C, Deonizio JM, Netto CA, Achaval M (2005) A simple and fast densitometric method for the analysis of tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta and in the ventral tegmental area. Brain Res Brain Res Protoc 16:58–64PubMedCrossRef

Yokoyama M, Black IB, Dreyfus CF (1993) NGF increases brain astrocyte number in culture. Exp Neurol 124:377–380PubMedCrossRef

Yoon MC, Shin MS, Kim TS, Kim BK, Ko IG, Sung YH, Kim SE, Lee HH, Kim YP, Kim CJ (2007) Treadmill exercise suppresses nigrostriatal dopaminergic neuronal loss in 6-hydroxydopamine-induced Parkinson’s rats. Neurosci Lett 423:12–17PubMedCrossRef

Yuan Y, Xue X, Guo RB, Sun XL, Hu G (2012) Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway. CNS Neurosci Ther 18:536–546PubMedCrossRef

Zhang M, Li WB, Liu YX, Liang CJ, Liu LZ, Cui X, Gong JX, Gong SJ, Hua YY, Xian XH (2011) High expression of GLT-1 in hippocampal CA3 and dentate gyrus subfields contributes to their inherent resistance to ischemia in rats. Neurochem Int 59:1019–1028PubMedCrossRef

Title: Physical exercise increases GFAP expression and induces morphological changes in hippocampal astrocytes
Authors: Lisiani Saur
Pedro Porto Alegre Baptista
Priscylla Nunes de Senna
Mariana Fontoura Paim
Patricia do Nascimento
Jocemar Ilha
Pamela Brambilla Bagatini
Matilde Achaval
Léder Leal Xavier
Publication date: 01-01-2014
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 1/2014
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-012-0500-8

At a glance: The STEP trials

Springer Medicine

Physical exercise increases GFAP expression and induces morphological changes in hippocampal astrocytes

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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