Skip to main content
Log in

Early molecular events in the hippocampus of rats with streptozotocin-induced diabetes

  • Published:
Neurophysiology Aims and scope

Abstract

In our study, we tried to find whether changes in expressions of inducible nitric oxide synthase (iNOS), corticosteroid (gluco-and mineralocorticoid) receptors (GRs and MRs, respectively), and bcl2 protein within the early stages of streptozotocin (STZ)-induced diabetes in Wistar rats can be involved in hippocampal dysfunction. Expressions of iNOS and bcl2 were studied using indirect immunofluorescence techniques, while GR and MR expressions were estimated using in situ mRNA hybridization. The concentrations of insulin, ACTH, and corticosterone in the blood serum were measured using ELISA kits. It was found that expression of iNOS in the CA2 and CA3 hippocampal areas increased significantly at day 3 after STZ injection, and corticosterone and ACTH levels in the serum increased at day 14. The iNOS expression was downregulated at day 14 of the development of diabetes. These changes were accompanied by significantly increased expression of GRs in the hippocampus. Neither bcl2 nor MR expression increased in the CA2 and CA3 hippocampal areas within the examined period of the development of diabetes. Thus, we first obtained proof of noticeable early molecular events in the rat hippocampus related to experimental diabetes. These events may be linked with diabetes-associated cognitive decline observed in patients suffering from diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. G. J. Biessels, L. P. van der Heide, A. Kamal, et al., “Ageing and diabetes: implications for brain function,” Eur. J. Pharmacol., 441, Nos. 1/2, 1–14 (2002).

    Article  PubMed  CAS  Google Scholar 

  2. G. S. Minhourt, P. Scheltens, M. Diamant, et al., “Diabetic encephalopathy: a concept in need of definition,” Diabetologia, 49, 1447–1448 (2006).

    Article  Google Scholar 

  3. 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 

  4. 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 

  5. S. Amrani, M. Durant, J. Throsby, et al., “Glucose homeostasis in the nonobese diabetic mouse at the prediabetic stage,” Endocrinology, 139, 1115–1124 (1998).

    Article  PubMed  CAS  Google Scholar 

  6. 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  Google Scholar 

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

    Article  PubMed  Google Scholar 

  8. 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 

  9. 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 

  10. 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 

  11. 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 

  12. 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 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. A. Orlovsky.

Additional information

Neirofiziologiya/Neurophysiology, Vol. 39, No. 6, pp. 498–502, November–December, 2007.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Orlovsky, M.A., Spiga, F., Lebed, Y.V. et al. Early molecular events in the hippocampus of rats with streptozotocin-induced diabetes. Neurophysiology 39, 435–438 (2007). https://doi.org/10.1007/s11062-008-9000-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11062-008-9000-0

Keywords

Navigation