Skip to main content

Advertisement

SpringerLink
Log in

Effects of physical exercise on spatial memory and astroglial alterations in the hippocampus of diabetic rats

  • Original Paper
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Type 1 diabetes mellitus (T1DM) is associated with neurocognitive dysfunction and astrogliosis. Physical exercise prevents cognitive impairments and induces important brain modifications. The aim of our study was to investigate the effect of treadmill exercise on spatial memory and astrocytic function in the hippocampus of a T1DM model. Fifty-seven Wistar rats were divided into four groups: trained control (TC) (n = 15), non-trained control (NTC) (n = 13), trained diabetic (TD) (n = 14) and non-trained diabetic (NTD) (n = 15). One month after streptozotocin-induced diabetes, exercise groups were submitted to 5 weeks of physical training, and then, all groups were assessed in the novel object-placement recognition task. Locomotor activity was analyzed in the open field apparatus using Any-maze software. The expression of glial fibrillary acidic protein (GFAP) and S100B in hippocampus and cerebrospinal fluid were measured using ELISA assay, and hippocampal GFAP immunoreactivity was evaluated by means of immunohistochemistry and optical densitometry. The results showed that physical exercise prevents and/or reverts spatial memory impairments observed in NTD animals (P < 0.01). Decreased locomotor activity was observed in both the NTD and TD groups when compared with controls (P < 0.05). ELISA and immunohistochemistry analyzes showed there was a reduction in GFAP levels in the hippocampus of NTD animals, which was not found in TD group. ELISA also showed an increase in S100B levels in the cerebrospinal fluid from the NTD group (P < 0.01) and no such increase was found in the TD group. Our findings indicate that physical exercise prevents and/or reverts the cognitive deficits and astroglial alterations induced by T1DM.

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

Similar content being viewed by others

References

  • Alaei HA, Moloudi RA, Sarkaki AR, Azizi-Malekabadi H, Hanninen O (2007) Daily running promotes spatial learning and memory in rats. Pathophysiology 14:105–108

    Article  PubMed  Google Scholar 

  • Alaei HA, Moloudi RA, 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 12:72–75

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Alvarez EO, Beauquis J, Revsin Y, Banzan AM, Roig P, De Nicola AF, Saraiva F (2009) Cognitive dysfunction and hippocampal changes in experimental type 1 diabetes. Behav Brain Res 198:224–230

    Article  PubMed  CAS  Google Scholar 

  • Baydas G, Nedzvetskii VS, Tuzcu M, Yasar A, Kirichenko SV (2003) Increase of glial fibrillary acidic protein and S-100B in hippocampus and cortex of diabetic rats: effects of vitamin E. Eur J Pharmacol 462:67–71

    Article  PubMed  CAS  Google Scholar 

  • Bartosik-Psujek H, Psujek M, Jaworski J, Stelmasiak Z (2010) Total tau and S100b proteins in different types of multiple sclerosis and during immunosuppressive treatment with mitoxantrone. Acta Neurol Scand 123:252–256

    Article  Google Scholar 

  • Beauquis J, Roig P, Homo-Delarche F, De Nicola A, Saravia F (2006) Reduced hippocampal neurogenesis and number of hilar neurons in streptozotocina-induced diabetic mice: reversion by antidepressant treatment. Eur J Neurosci 23:1539–1546

    Article  PubMed  Google Scholar 

  • Biessels GJ, Kamal A, Urban IJ, Spruijt BM, Erkelens DW, Gispen WH (1998) Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: effects of insulin treatment. Brain Res 800:125–135

    Article  PubMed  CAS  Google Scholar 

  • Blyth BJ, Farhavar A, Gee C, Hawthorn B, He H, Nayak A, Stocklein V, Bazarian JJ (2009) Validation of serum markers for blood-brain barrier disruption in traumatic brain injury. J Neurotrauma 26:1497–1507

    Article  PubMed  Google Scholar 

  • Cavaglia M, Dombrowski SM, Drazba J, Vasanji A, Bokeschb PM, Janigro D (2001) Regional variation in brain capillary density and vascular response to ischemia. Brain Res 910:81–93

    Article  PubMed  CAS  Google Scholar 

  • Coleman ES, Judd RL, Hoel J, Dennis J, Posner P (2004) Effects of diabetes mellitus on astrocyte GFAP and glutamate transporters in the CNS. Glia 48:166–178

    Article  PubMed  Google Scholar 

  • D’Ercole AD, Ye P (2008) Minireview: expanding the mind: insulin-like growth factor I and brain development. Endocrinology 149:5958–5962

    Article  Google Scholar 

  • Dere E, Huston JP, Souza Silva MA (2005) Episodic-like memory in mice:Simultaneous assessment of object, place and temporal order memory. Brain Res Prot 16:10–19

    Article  Google Scholar 

  • Do Nascimento PS, Malysz T, Ilha J, Araujo RT, Hermel EE, Kalil-Gaspar PI, Faccioni-Heuser MC, Schaan BD, Achaval M (2010) Treadmill training increases the size of A cells from the L5 dorsal root ganglia in diabetic rats. Histol Histopathol 25:719–732

    PubMed  Google Scholar 

  • Do Nascimento PS, Lovatel GA, Barbosa S, Ilha J, Centanaro LA, Malysz T, Xavier LL, Schaann BD, Achaval M (2011) Treadmill training improves motor skills and increases tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta in diabetic rats. Brain Res 1382:173–180

    Article  CAS  Google Scholar 

  • Gardoni F, Kamal A, Bellone C, Biessels GJ, Ramarkers GM, Cattabeni F, Gispen WH, Di Luca M (2002) Effects of streptozotocin-diabetes on the hippocampal NMDA receptor complex in rats. J Neurochem 3:438–447

    Article  Google Scholar 

  • Gomes da Silva S, Unsain N, Masco DH, Toscano-Silva M, de Amorin HA, Silva Araújo BH, Simões PS, da Graça Naffah-Mazzacoratti M, Mortara RA, Scorza FA, Cavalheiro EA, Arida RM (2010) Early exercise promotes positive hippocampal plasticity and improves spatial memory in the adult life of rats. Hippocampus. doi:10.1002/hipo.20903

  • Gonçalves CA, Leite MC, Nardin P (2008) Biological and methodological features of the measurement of S100B, a putative marker of brain injury. Clin Biochem 41:755–763

    Article  PubMed  Google Scholar 

  • Griffin WS, Stamley LC, Ling C, White L, Macleod V, Perrot LJ, White CL, Araoz C (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 86:7611–7615

    Article  PubMed  CAS  Google Scholar 

  • Grzęda E, Wiśniewska R (2008) Differentiations of the effect of NMDA on the spatial learning of rats with 4 and 12 week diabetes mellitus. Acta Neurobiol Exp 68:398–406

    Google Scholar 

  • Guo M, Cox B, Mahale S, Davis W, Carranza A, Hayes K, Spraque S, Jimenez D, Ding Y (2008) Pre-ischemic exercise reduces matrix metalloproteinase-9 expression and ameliorates blood-brain barrier dysfunction in stroke. Neuroscience 151:340–351

    Article  PubMed  CAS  Google Scholar 

  • Hawkins CL, Davies MJ (2001) Generation and propagation of radical reactions on proteins. Biochim Biophys Acta 1504:196–219

    Article  PubMed  CAS  Google Scholar 

  • Ilha J, Araujo RT, Malysz T, Hermel EE, Rigon P, Xavier LL, Achaval M (2008) Endurance and resistance exercise training programs elicit specific effects on sciatic nerve regeneration after experimental traumatic lesion in rats. Neurorehabil Neural Repair 22:355–366

    PubMed  Google Scholar 

  • Kamal A, Biessels GJ, Urban IJ, Gispen WH (1999) Hippocampal synaptic plasticity in streptozotocin diabetic rats: impairment of long-term potentiation and facilitation of long-term depression. Neurosci 90:737–745

    Article  CAS  Google Scholar 

  • 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 Diabet Complications 17:29–33

    Article  Google Scholar 

  • Kleindienst A, Mcginn MJ, Harvey HB, Collejo RJ, Hamm RJ, Bullock MR (2005) Enhanced hippocampal neurogenesis by intraventricular S100B infusion is associated with improved cognitive recovery after traumatic brain injury. J Neurotrauma 22:645–655

    Article  PubMed  Google Scholar 

  • Kleindienst A, Bullock MR (2006) A critical analysis of the role of the neurotrophic protein S100B in acute brain injury. J Neurotrauma 23:1185–1200

    Article  PubMed  Google Scholar 

  • Lebed YV, Orlovsky MA, Nikonenko AG, Ushakova GA, Skibo GG (2008) Early reaction of astroglial cells in rat hippocampus to streptozotocin-induced diabetes. Neurosci Lett 444:181–185

    Article  PubMed  CAS  Google Scholar 

  • Lechuga-Sancho AM, Arroba A, Frago LM, García-Cáceres C, Célix ADR, Argente J, Chowen JA (2006a) Reduction in the number of astrocytes and their projections is associated with increased synaptic protein density in the hypothalamus of poorly controlled diabetic rats. Endocrinology 47:5314–5324

    Article  Google Scholar 

  • Lechuga-Sancho AM, Arroba A, Frago LM, Pañeda C, García-Cáceres C, Célix ADR, Argente J, Chowen JA (2006b) Activation of the intrinsic cell death pathway, increased apoptosis and modulation of astrocytes in the cerebellum of diabetic rats. Neurobiol Dis 23:290–299

    Article  PubMed  CAS  Google Scholar 

  • Leite MC, Galland F, Brolese G, Guerra MC, Bortolotto JW, Freitas R, Almeida LM, Gottfried C, Gonçalves CA (2008) A simple, sensitive and widely applicable ELISA for S100B: methodological features of the measurement of this glial protein. J Neurosci Methods 169:93–99

    Article  PubMed  CAS  Google Scholar 

  • Li ZG, Zhang W, Grunberger G, Sima A (2002) Hippocampal neuronal apoptosis in type 1 diabetes. Brain Res 946:221–231

    Article  PubMed  CAS  Google Scholar 

  • Li C, Brake WG, Romeo RD, Dunlop JC, Gordon M, Buzescu R et al (2004) Estrogen alters hippocampal dendritic spine shape and enhances synaptic protein immunoreactivity and spatial memory in female mice. Proc Natl Acad Sci USA 101:2185–2190

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lista I, Sorrentino G (2010) Biological mechanisms of physical activity in preventing cognitive decline. Cell Mol Neurobiol 30:493–503

    Article  PubMed  CAS  Google Scholar 

  • Malysz T, Ilha J, Do Nascimento PS, De Angelis K, D’agord Schaan B, Achaval M (2010) Beneficial effects of treadmill training in experimental diabetic nerve regeneration. Clinics (Sao Paulo) 65:1329–1337

    Google Scholar 

  • Marchi N, Rasmussen P, Kapural M, Fazio V, Kight K, Mayberg MR, Kanner A, Ayumar B, Albensi B, Cavaglia M, Janigro D (2003) Peripheral markers of brain damage and blood–brain barrier dysfunction. Restor Neurol Neurosci 21:109–121

    PubMed  CAS  Google Scholar 

  • Melo RM, Martinho E Jr, Michelini LC (2003) Training-induced pressure-lowering effect in SHR: wide effects on circulatory profile of exercised and non exercised muscles. Hypertension 42:851–857

    Article  PubMed  CAS  Google Scholar 

  • Munehiro U, 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 1104:64–72

    Article  Google Scholar 

  • Nardin P, Tramontina F, Leite MC, Tramontina AC, Quincozes-Santos A, de Almeida LM, Battastini AM, Gottfried C, Gonçalves CA (2007) S100B content and secretion decrease in astrocytes cultured in high-glucose medium. Neurochem Int 50:774–782

    Article  PubMed  CAS  Google Scholar 

  • Ohira K, Funatsu N, Homma KJ, Sahara Y, Hayashi M, Kaneko T, Nakamura S (2007) Truncated TrkB-T1 regulates the morphology of neocortical layer 1 astrocytes in adult rat brain slices. Eur J Neurosci 25:406–416

    Article  PubMed  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic Press, San Diego

  • Piazza FV, Pinto GV, Trott G, Marcuzzo S, Gomez R, Fernandes MC (2010) Enriched environment prevents memory deficits in type 1 diabetic rats. Behav Brain Res 217:16–20

    Article  PubMed  Google Scholar 

  • Ma Q (2008) Beneficial effects of moderate voluntary physical exercise and its biological mechanisms on brain health. Neurosci Bull 24:265–270

    Article  PubMed  CAS  Google Scholar 

  • Ra SM, Kim H, Jang MH, Shin MC, Lee TH, Lim BV, Kim CL, Kim EH, Kim KM, Kim SS (2002) Treadmill running and swimming increase cell proliferation in the hippocampal dentate gyrus of rats. Neurosci Lett 333:123–126

    Article  PubMed  CAS  Google Scholar 

  • Reisi P, Alaei H, Babri S, Sharifi MR, Mohaddes G (2009) Effects of treadmill running on spatial learning and memory in streptozotocin-induced diabetic rats. Neurosci Lett 455:79–83

    Article  PubMed  CAS  Google Scholar 

  • Reisi P, Babri S, Alaei H, Sharifi MR, Mohaddes G, Noorbakhsh SM, Lashgari R (2010) Treadmill running improves long-term potentiation (LTP) defects in streptozotocin-induced diabetes at dentate gyrus in rats. Pathophysiology 17:33–38

    Article  PubMed  Google Scholar 

  • Revsin Y, Rekers NV, Louwe MC, Saravia FE, Nicola AF, Kloet ER, Oitzl MS (2009) Glucocorticoid receptor blockade normalizes hippocampal alterations and cognitive impairment in streptozotocin-induced type 1 diabetes mice. Neuropsychopharmacology 34:747–758

    Article  PubMed  CAS  Google Scholar 

  • Rodrigues B, Figueroa DM, Mostarda CT, Heeren MV, Irigoyen MC, De Angelis K (2007) Maximal exercise test is a useful method for physical capacity and oxygen consumption determination in streptozotocin-diabetic rats. Cardiovasc Diabetol 13:6–38

    Google Scholar 

  • Roriz-Filho J, Sá-Roriz TM, Rosset I, Camozzato AL, Santos AC, Chaves ML, Moriguti JC, Roriz-Cruz M (2009) (Pre)diabetes, brain aging, and cognition. Biochim Biophys Acta 1792:432–443

    CAS  Google Scholar 

  • Rothermundt M, Peters M, Prehn JH, Arolt V (2003) S100B in brain damage and neurodegeneration. Microsc Res and Tech 60:614–632

    Article  CAS  Google Scholar 

  • Schmidt H, Gerber J, Stuartz K, Djukic M, Bunkowski S, Fischer FR, Otto M, Nau R (2010) S100B in the cerebrospinal fluid- a marker for glial damage in the rabbit model of pneumococcal meningitis. Neurosci Lett 475:104–107

    Article  PubMed  CAS  Google Scholar 

  • Sternberger LA (1979) The unlabeled antibody (PAP) method, introduction. J Histochem Cytochem 27:1657

    Article  PubMed  CAS  Google Scholar 

  • Stranahan AM, Lee K, Becker KG, Zhang Y, Maudsley S, Martin B, Cutler RG, Mattson MP (2008) Hippocampal gene expression patterns underlying the enhancement of aging memory by running in aged mice. Neurobiol Aging 31:1937–1949

    Article  PubMed  Google Scholar 

  • Tramontina F, Leite MC, Cereser K, Souza DF, Tramontina AC, Nardin P, Andreazza AC, Gottfried C, Kapczinski F, Gonçalves CA (2007) Immunoassay for glial fibrillary acidic protein: antigen recognition is affected by its phosphorylation state. J Neurosci Methods 162:282–286

    Article  PubMed  CAS  Google Scholar 

  • Tuzcu M, Baydas G (2006) Effect of melatonin and vitamin E on diabetes-induced learning and memory impairment in rats. Europ J Pharmacol 537:106–110

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • VanGilder RL, Kelly KA, Chua MD, Ptachcinski RL, Huber JD (2009) Administration of sesamol improved blood–brain barrier function in streptozotocin-induced diabetic rats. Exp Brain Res 197:23–34

    Article  PubMed  CAS  Google Scholar 

  • Van Praag H, Kempermann G, Gage FH (1999a) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266–279

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Viola G, Rodrigues L, Américo J, Hansel G, Vargas R, 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 1274:47–54

    Article  PubMed  CAS  Google Scholar 

  • Wessels AM, Scheltens P, Barkhof F, Heine RJ (2008) Hyperglycaemia as a determinant of cognitive decline in patients with type 1 diabetes. Eur J Pharmacol 585:88–96

    Article  PubMed  CAS  Google Scholar 

  • Xavier LL, Viola G, Ferraz AC, Cunha C, Deonizio JMD, 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 Prot 16:58–64

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by UFRGS and the Brazilian funding agencies National Council for Scientific and Technological Development (CNPq) and Coordination for the Improvement of Higher Education Personnel (CAPES). We are grateful to Silvia Barbosa and Antonio Generoso Severino for their technical assistance. Priscylla Senna was supported by an MSc scholarship from CAPES and Carlos Alberto Gonçalves, Matilde Achaval and Léder Leal Xavier are CNPq investigators.

Conflict of Interest

The authors declare that they have no conflict of interest

Author information

Authors and Affiliations

  1. Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil

    Priscylla Nunes de Senna, Jocemar Ilha, Patrícia Severo do Nascimento, Carlos Alberto Gonçalves & Matilde Achaval

  2. Laboratório de Histofisiologia Comparada, Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil

    Priscylla Nunes de Senna, Jocemar Ilha, Patrícia Severo do Nascimento & Matilde Achaval

  3. Laboratório de Biologia Celular e Tecidual, Departamento de Ciências Morfofisiológicas, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga 6681, prédio 12, sala 144, Porto Alegre, RS, Brasil, CEP 90619-900

    Pedro Porto Alegre Baptista, Mariana Fontoura Paim & Léder Leal Xavier

  4. Departamento de Bioquímica, Instituto de Ciências Básica da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil

    Marina Concli Leite & Carlos Alberto Gonçalves

Authors
  1. Priscylla Nunes de Senna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jocemar Ilha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pedro Porto Alegre Baptista
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patrícia Severo do Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marina Concli Leite
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mariana Fontoura Paim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carlos Alberto Gonçalves
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Matilde Achaval
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Léder Leal Xavier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Léder Leal Xavier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Senna, P.N., Ilha, J., Baptista, P.P.A. et al. Effects of physical exercise on spatial memory and astroglial alterations in the hippocampus of diabetic rats. Metab Brain Dis 26, 269–279 (2011). https://doi.org/10.1007/s11011-011-9262-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-011-9262-x

Keywords

Search

Navigation