JOURNAL ARTICLE

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
Journal of Neural Transmission 2017, 124 (6): 695-708
28470423
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.

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