Skip to main content
SpringerLink
Log in

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

  • Published:
Neurophysiology Aims and scope

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.

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

Similar content being viewed by others

References

  1. G. J. Biessels, “Cerebral complications of diabetes: clinical findings and pathogenetic mechanisms,” Neth. J. Med., 54, 35–45 (1999).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  7. R. Prikryl, “Cognitive functions impairment in diabetes mellitus patients,” Cas. Lek. Cesk., 146, 434–437 (2007).

    PubMed  CAS  Google Scholar 

  8. C. M. Ryan, “Diabetes, aging, and cognitive decline,” Neurobiol. Aging, 26, 21–25 (2005).

    Article  PubMed  Google Scholar 

  9. I. Tuma, “Diabetes mellitus and cognitive impairments,” Vnitr. Lek., 53, 486–488 (2007).

    PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  15. M. A. Orlovsky, “Regularities of formation of hyperglycemia under conditions of experimental diabetes mellitus,” Patologiya, 1, 52–56 (2004).

    Google Scholar 

  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).

    Article  CAS  Google Scholar 

  17. R. J. Mullen, C. R. Buck, and A. M. Smith, “NeuN, a neuronal specific nuclear protein in vertebrates,” Development, 116, 201–211 (1992).

    PubMed  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  PubMed  Google Scholar 

  21. H. B. Lee and M. D. Blaufox, “Blood volume in the rat,” J. Nucl. Med., 26, 72–76 (1985).

    PubMed  CAS  Google Scholar 

  22. O. Chan, K. Inouye, M. C. Riddell, et al., “Diabetes and the hypothalamo-pituitary-adrenal (HPA) axis,” Minerva Endocrinol., 28, 87–102 (2003).

    PubMed  CAS  Google Scholar 

  23. T. Kovalenko, I. Osadchenko, A. Nikonenko, et al., “Ischemia-induced modifications in hippocampal CA1 stratum radiatum excitatory synapses,” Hippocampus, 16, 814–825 (2006).

    Article  PubMed  CAS  Google Scholar 

  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. R. M. Sapolsky, “Potential behavioral modification of glucocorticoid damage to the hippocampus,” Behav. Brain Res., 57, 175–182 (1993).

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  39. G. Buzsaki, “Theta rhythm of navigation: link between path integration and landmark navigation, episodic and semantic memory,” Hippocampus, 15, 827–840 (2005).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Bogomolets Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine

    Yu. V. Lebed, M. A. Orlovsky, I. V. Lushnikova & G. G. Skibo

Authors
  1. Yu. V. Lebed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. A. Orlovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. V. Lushnikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. G. Skibo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yu. V. Lebed.

Additional information

Neirofiziologiya/Neurophysiology, Vol. 40, No. 1, pp. 30–37, January–February, 2008.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lebed, Y.V., Orlovsky, M.A., Lushnikova, I.V. et al. Neurodegenerative changes in the hippocampus within the early period of experimental diabetes mellitus . Neurophysiology 40, 26–33 (2008). https://doi.org/10.1007/s11062-008-9019-2

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11062-008-9019-2

Keywords

Search

Navigation