Journal of Neural Transmission

, Volume 124, Issue 6, pp 695–708 | Cite as

Rat brain glucose transporter-2, insulin receptor and glial expression are acute targets of intracerebroventricular streptozotocin: risk factors for sporadic Alzheimer’s disease?

  • A. Knezovic
  • A. Loncar
  • J. Homolak
  • U. Smailovic
  • J. Osmanovic Barilar
  • L. Ganoci
  • N. Bozina
  • P. Riederer
  • Melita Salkovic-Petrisic
Translational Neurosciences - Original Article


Accumulated evidence suggests that the insulin-resistant brain state and cerebral glucose hypometabolism might be the cause, rather than the consequence, of the neurodegeneration found in a sporadic Alzheimer’s disease (sAD). We have explored whether the insulin receptor (IR) and the glucose transporter-2 (GLUT2), used here as their markers, are the early targets of intracerebroventricularly (icv) administered streptozotocin (STZ) in an STZ-icv rat model of sAD, and whether their changes are associated with the STZ-induced neuroinflammation. The expression of IR, GLUT2 and glial fibrillary acidic protein (GFAP) was measured by immunofluorescence and western blot analysis in the parietal (PC) and the temporal (TC) cortex, in the hippocampus (HPC) and the hypothalamus. One hour after the STZ-icv administration (1.5 mg/kg), the GFAP immunoreactivity was significantly increased in all four regions, thus indicating the wide spread neuroinflammation, pronounced in the PC and the HPC. Changes in the GLUT2 (increment) and the IR (decrement) expression were mild in the areas close to the site of the STZ injection/release but pronounced in the ependymal lining cells of the third ventricle, thus indicating the possible metabolic implications. These results, together with the finding of the GLUT2-IR co-expression, and also the neuronal IR expression in PC, TC and HPC, indicate that the cerebral GLUT2 and IR should be further explored as the possible sAD etiopathogenic factors. It should be further clarified whether their alterations are the effect of a direct STZ-icv toxicity or they are triggered in a response to STZ-icv induced neuroinflammation.


Streptozotocin Alzheimer’s disease Glucose transporter 2 Insulin receptor 



Supported by University of Zagreb (funds awarded to M. Salkovic-Petrisic, 2015–2016), AMAC-UK (funds awarded to U. Smailovic, 2013) and the Edda Neele Stiftung (funds awarded to M. Salkovic-Petrisic). Z. Mikloska, Ph.D. is thanked for English editing.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

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© Springer-Verlag Wien 2017

Authors and Affiliations

  • A. Knezovic
    • 1
  • A. Loncar
    • 1
    • 2
  • J. Homolak
    • 1
  • U. Smailovic
    • 1
    • 3
  • J. Osmanovic Barilar
    • 1
  • L. Ganoci
    • 4
  • N. Bozina
    • 1
    • 4
  • P. Riederer
    • 5
  • Melita Salkovic-Petrisic
    • 1
  1. 1.Department of Pharmacology and Croatian Institute for Brain ResearchUniversity of Zagreb School of MedicineZagrebCroatia
  2. 2.Department of NeurologyGeneral Hospital KarlovacKarlovacCroatia
  3. 3.Department of Neurobiology, Care Sciences and Society, Division of Clinical GeriatricsKarolinska InstituteStockholmSweden
  4. 4.Department of Laboratory DiagnosticsUniversity Hospital Centre ZagrebZagrebCroatia
  5. 5.Centre of Mental Health, Department of Psychiatry, Psychosomatics, and PsychotherapyUniversity Hospital of WürzburgWürzburgGermany

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