Neurophysiology

, 40:26 | Cite as

Neurodegenerative changes in the hippocampus within the early period of experimental diabetes mellitus

  • Yu. V. Lebed
  • M. A. Orlovsky
  • I. V. Lushnikova
  • G. G. Skibo
Article
First Online:
Received:

Abstract

We studied the dynamics of modifications of the structure and architectonics in different zones of the pyramidal layer of the rat hippocampus within the early periods (3, 7, and 14 days) after induction of diabetes mellitus by streptozotocin. Using confocal immunofluorescence microscopy, we found neurons containing a specific protein, NeuN; a fluorescence dye, Hoechst 33258, allowed us to visualize the cell nuclei. The density of localization of neurons in the CA2 area decreased significantly on the 3rd day of development of diabetes. In the CA1 and CA3 areas, a significant decrease in this index was observed beginning from the 7th day. Within this time interval, we observed neurons with clear condensation of chromatin in the nuclei of these cells. The obtained data indicate that formation of appreciable neurodegenerative changes in the hippocampus occurs within the initial stages of development of experimental diabetes mellitus; this phenomenon can be a factor in the development of diabetic encephalopathy.

Keywords

diabetes mellitus hippocampus neurodegeneration streptozotocin 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    G. J. Biessels, “Cerebral complications of diabetes: clinical findings and pathogenetic mechanisms,” Neth. J. Med., 54, 35–45 (1999).PubMedCrossRefGoogle Scholar
  2. 2.
    G. J. Biessels, L. P. van der Heide, A. Kamal, et al., “Ageing and diabetes: implications for brain function,” Eur. J. Pharmacol., 441, 1–14 (2002).PubMedCrossRefGoogle Scholar
  3. 3.
    A. M. Brands, G. J. Biessels, L. J. Kappelle, et al., “Cognitive functioning and brain MRI in patients with type 1 and type 2 diabetes mellitus: a comparative study,” Dement. Geriat. Cogn. Disord., 23, 343–350 (2007).CrossRefGoogle Scholar
  4. 4.
    G. J. Biessels and W. H. Gispen, “The impact of diabetes on cognition: what can be learned from rodent models?” Neurobiol. Aging, 26, 36–41 (2005).PubMedCrossRefGoogle Scholar
  5. 5.
    C. M. Ryan and T. M. Williams, “Effects of insulin-dependent diabetes on learning and memory efficiency in adults,” J. Clin. Exp. Neuropsychol., 15, 685–700 (1993).PubMedCrossRefGoogle Scholar
  6. 6.
    A. M. Wessels, S. A. Rombouts, P. L. Remijnse, et al., “Cognitive performance in type 1 diabetes patients is associated with cerebral white matter volume,” Diabetologia, 50, 1763–1769 (2007).PubMedCrossRefGoogle Scholar
  7. 7.
    R. Prikryl, “Cognitive functions impairment in diabetes mellitus patients,” Cas. Lek. Cesk., 146, 434–437 (2007).PubMedGoogle Scholar
  8. 8.
    C. M. Ryan, “Diabetes, aging, and cognitive decline,” Neurobiol. Aging, 26, 21–25 (2005).PubMedCrossRefGoogle Scholar
  9. 9.
    I. Tuma, “Diabetes mellitus and cognitive impairments,” Vnitr. Lek., 53, 486–488 (2007).PubMedGoogle Scholar
  10. 10.
    A. Kamal, G. J. Biessels, G. M. Ramakers, et al., “The effect of short duration streptozotocin-induced diabetes mellitus on the late phase and threshold of long-term potentiation induction in the rat,” Brain Res., 1053, 126–130 (2005).PubMedCrossRefGoogle Scholar
  11. 11.
    A. Kamal, G. J. Biessels, I. J. Urban, et al., “Hippocampal synaptic plasticity in streptozotocin-diabetic rats: impairment of long-term potentiation and facilitation of long-term depression,” Neuroscience, 90, 737–745 (1999).PubMedCrossRefGoogle Scholar
  12. 12.
    C. A. Grillo, G. G. Piroli, G. E. Wood, et al., “Immunocytochemical analysis of synaptic proteins provides new insights into diabetes-mediated plasticity in the rat hippocampus,” Neuroscience, 136, 477–486 (2005).PubMedCrossRefGoogle Scholar
  13. 13.
    A. M. Magarinos and B. S. McEwen, “Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress,” Proc. Natl. Acad. Sci. USA, 97, 11056–11061 (2000).PubMedCrossRefGoogle Scholar
  14. 14.
    Y. Revsin, F. Saravia, P. Roig, et al., “Neuronal and astroglial alterations in the hippocampus of a mouse model for type 1 diabetes,” Brain Res., 1038, 22–31 (2005).PubMedCrossRefGoogle Scholar
  15. 15.
    M. A. Orlovsky, “Regularities of formation of hyperglycemia under conditions of experimental diabetes mellitus,” Patologiya, 1, 52–56 (2004).Google Scholar
  16. 16.
    G. Baydas, E. Sonkaya, M. Tuzcu, et al., “Novel role for gabapentin in neuroprotection of central nervous system in streptozotocin-induced diabetic rats,” Acta Pharmacol. Sin., 4, 417–422 (2005).CrossRefGoogle Scholar
  17. 17.
    R. J. Mullen, C. R. Buck, and A. M. Smith, “NeuN, a neuronal specific nuclear protein in vertebrates,” Development, 116, 201–211 (1992).PubMedGoogle Scholar
  18. 18.
    M. Saito, M. Kobayashi, S. Iwabuchi, et al., “DNA condensation monitoring after interaction with hoechst 33258 by atomic force microscopy and fluorescence spectroscopy,” J. Biochem., 6, 813–823 (2004).CrossRefGoogle Scholar
  19. 19.
    L. Stoppini, P. A. Buchs, and D. Muller, “A simple method for organotypic cultures of nervous tissue,” J. Neurosci. Method, 37, 173–182 (1991).CrossRefGoogle Scholar
  20. 20.
    M. Bottlang, M. B. Sommers, T. A. Lusardi, et al., “Modeling neural injury in organotypic cultures by application of inertia-driven shear strain,” J. Neurotrauma, 24, 1068–1077 (2007).PubMedCrossRefGoogle Scholar
  21. 21.
    H. B. Lee and M. D. Blaufox, “Blood volume in the rat,” J. Nucl. Med., 26, 72–76 (1985).PubMedGoogle Scholar
  22. 22.
    O. Chan, K. Inouye, M. C. Riddell, et al., “Diabetes and the hypothalamo-pituitary-adrenal (HPA) axis,” Minerva Endocrinol., 28, 87–102 (2003).PubMedGoogle Scholar
  23. 23.
    T. Kovalenko, I. Osadchenko, A. Nikonenko, et al., “Ischemia-induced modifications in hippocampal CA1 stratum radiatum excitatory synapses,” Hippocampus, 16, 814–825 (2006).PubMedCrossRefGoogle Scholar
  24. 24.
    G. G. Skibo, T. M. Kovalenko, I. O. Osadchenko, et al., “Structural changes in the hippocampus in experimental cerebral ischemia,” Ukr. Nevrol. Zh., 4, 38–44 (2006).Google Scholar
  25. 25.
    R. M. Sapolsky, “Potential behavioral modification of glucocorticoid damage to the hippocampus,” Behav. Brain Res., 57, 175–182 (1993).PubMedCrossRefGoogle Scholar
  26. 26.
    R. M. Sapolsky, H. Uno, C. S. Rebert, et al., “Hippocampal damage associated with prolonged glucocorticoid exposure in primates,” J. Neurosci., 10, 2897–2902 (1990).PubMedGoogle Scholar
  27. 27.
    D. F. Swaab, A. M. Bao, and P. J. Lucassen, “The stress system in the human brain in depression and neurodegeneration,” Ageing Res. Rev., 4, 141–194 (2005).PubMedCrossRefGoogle Scholar
  28. 28.
    P. J. Lucassen, V. M. Heine, M. B. Muller, et al., “Stress, depression and hippocampal apoptosis,” CNS Neurol. Disord. Drug Targets, 5, 531–546 (2006).PubMedCrossRefGoogle Scholar
  29. 29.
    S. Rossie, H. Jayachandran, and R. L. Meisel, “Cellular co-localization of protein phosphatase 5 and glucocorticoid receptors in rat brain,” Brain Res., 1111, 1–11 (2006).PubMedCrossRefGoogle Scholar
  30. 30.
    M. P. Armanini, C. Hutchins, B. A. Stein, et al., “Glucocorticoid endangerment of hippocampal neurons is NMDA-receptor dependent,” Brain Res., 532, 7–12 (1990).PubMedCrossRefGoogle Scholar
  31. 31.
    J. A. Van Eekelen and E. R. de Kloet, “Co-localization of brain corticosteroid receptors in the rat hippocampus,” Prog. Histochem. Cytochem., 26, 250–258 (1992).PubMedGoogle Scholar
  32. 32.
    G. Yang, M. F. Matocha, and S. I. Rapoport, “Localization of glucocorticoid receptor messenger ribonucleic acid in hippocampus of rat brain using in situ hybridization,” Mol. Endocrinol., 2, 682–685 (1988).PubMedGoogle Scholar
  33. 33.
    L. E. Haynes, M. R. Griffiths, R. E. Hyde, et al., “Dexamethasone induces limited apoptosis and extensive sublethal damage to specific subregions of the striatum and hippocampus: implications for mood disorders,” Neuroscience, 104, 57–69 (2001).PubMedCrossRefGoogle Scholar
  34. 34.
    S. Kang, J. Song, H. Kang, et al., “Insulin can block apoptosis by decreasing oxidative stress via phosphatidyl inositol 3-kinase-and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells,” Eur. J. Endocrinol., 148, 147–155 (2003).PubMedCrossRefGoogle Scholar
  35. 35.
    F. Bertrand, A. Atfi, A. Cadoret, et al., “A role for nuclear factor kappaB in the antiapoptotic function of insulin,” J. Biol. Chem., 5, 2931–2938 (1998).CrossRefGoogle Scholar
  36. 36.
    M. A. Orlovsky, F. Spiga, Y. V. Lebed, et al., “Early molecular events in the hippocampus of rats with streptozotocin-induced diabetes,” Neurophysiology, 39, No. 6, 435–438 (2007).CrossRefGoogle Scholar
  37. 37.
    F. Han, H. Ozawa, K. Matsuda, et al., “Colocalization of mineralocorticoid receptor and glucocorticoid receptor in the hippocampus and hypothalamus,” Neurosci. Res., 51, 371–381 (2005).PubMedCrossRefGoogle Scholar
  38. 38.
    A. Mercer, H. L. Trigg, and A. M. Thomson, “Characterization of neurons in the CA2 subfield of the adult rat hippocampus,” J. Neurosci., 27, 7329–7338 (2007).PubMedCrossRefGoogle Scholar
  39. 39.
    G. Buzsaki, “Theta rhythm of navigation: link between path integration and landmark navigation, episodic and semantic memory,” Hippocampus, 15, 827–840 (2005).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2008

Authors and Affiliations

  • Yu. V. Lebed
    • 1
  • M. A. Orlovsky
    • 1
  • I. V. Lushnikova
    • 1
  • G. G. Skibo
    • 1
  1. 1.Bogomolets Institute of PhysiologyNational Academy of Sciences of UkraineKyivUkraine

Personalised recommendations