Central nervous system complications of diabetes in streptozotocin-induced diabetic rats: a histopathological and immunohistochemical examination

Int J Neurosci. 2009;119(8):1155-69. doi: 10.1080/00207450902841723.


Diabetes mellitus is a common, potentially serious metabolic disorder. Over the long term, diabetes leads to serious consequences in a number of tissues, especially those that are insulin insensitive (retina, neurons, kidneys). It also causes a variety of functional and structural disorders in the central and peripheral nervous systems. We investigated whether neurodegenerative changes were observable in the hippocampus, cortex, and cerebellum after 4 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of melatonin. Male Wistar rats (n = 32) were divided into four groups (n = 8 each): untreated controls, melatonin-treated controls, untreated diabetics, and melatonin-treated diabetics. Experimental diabetes was induced by a single dose of STZ (60 mg/kg, intraperitoneal (ip)). For 3 days before the administration of STZ, melatonin (200 microg/kg/day, ip) was injected and continued for 4 weeks. Sections of hippocampus, cortex, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, brain tissues were examined immunohistochemically for the expression of glial and neuronal markers, including glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and heat shock protein-70 (HSP-70). No neurodegenerative changes were observed in the hippocampus, cortex, or cerebellum of the untreated diabetic group after 4 weeks compared with the other groups. We did not observe any change in GFAP, NSE, or HSP-70 immunostaining in the brain tissues of STZ-induced diabetic rats. In summary, after 4 weeks of STZ-induced diabetes in rats, no degenerative or immunohistochemical changes were detected in the hippocampus, cortex, or cerebellum.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Brain Chemistry / physiology
  • Central Nervous System Diseases / etiology*
  • Central Nervous System Diseases / pathology*
  • Cerebellum / pathology
  • Cerebral Cortex / pathology
  • Diabetes Complications / pathology*
  • Diabetes Mellitus, Experimental / pathology*
  • Glial Fibrillary Acidic Protein / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Hippocampus / pathology
  • Immunohistochemistry
  • Male
  • Melatonin / pharmacology
  • Neurodegenerative Diseases / chemically induced
  • Neurodegenerative Diseases / pathology
  • Phosphopyruvate Hydratase / metabolism
  • Rats
  • Rats, Wistar


  • Antioxidants
  • Glial Fibrillary Acidic Protein
  • HSP70 Heat-Shock Proteins
  • Phosphopyruvate Hydratase
  • Melatonin