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Rat brain glucose transporter-2, insulin receptor and glial expression are acute targets of intracerebroventricular streptozotocin: risk factors for sporadic Alzheimer's disease?
J Neural Transm (Vienna). 2017 06; 124(6):695-708.JN

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Salata 11, 10 000, Zagreb, Croatia.Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Salata 11, 10 000, Zagreb, Croatia. Department of Neurology, General Hospital Karlovac, Karlovac, Croatia.Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Salata 11, 10 000, Zagreb, Croatia.Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Salata 11, 10 000, Zagreb, Croatia. Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden.Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Salata 11, 10 000, Zagreb, Croatia.Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia.Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Salata 11, 10 000, Zagreb, Croatia. Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia.Centre of Mental Health, Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.Department of Pharmacology and Croatian Institute for Brain Research, University of Zagreb School of Medicine, Salata 11, 10 000, Zagreb, Croatia. melitas@mef.hr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28470423

Citation

Knezovic, A, et al. "Rat Brain Glucose Transporter-2, Insulin Receptor and Glial Expression Are Acute Targets of Intracerebroventricular Streptozotocin: Risk Factors for Sporadic Alzheimer's Disease?" Journal of Neural Transmission (Vienna, Austria : 1996), vol. 124, no. 6, 2017, pp. 695-708.
Knezovic A, Loncar A, Homolak J, et al. Rat brain glucose transporter-2, insulin receptor and glial expression are acute targets of intracerebroventricular streptozotocin: risk factors for sporadic Alzheimer's disease? J Neural Transm (Vienna). 2017;124(6):695-708.
Knezovic, A., Loncar, A., Homolak, J., Smailovic, U., Osmanovic Barilar, J., Ganoci, L., Bozina, N., Riederer, P., & Salkovic-Petrisic, M. (2017). Rat brain glucose transporter-2, insulin receptor and glial expression are acute targets of intracerebroventricular streptozotocin: risk factors for sporadic Alzheimer's disease? Journal of Neural Transmission (Vienna, Austria : 1996), 124(6), 695-708. https://doi.org/10.1007/s00702-017-1727-6
Knezovic A, et al. Rat Brain Glucose Transporter-2, Insulin Receptor and Glial Expression Are Acute Targets of Intracerebroventricular Streptozotocin: Risk Factors for Sporadic Alzheimer's Disease. J Neural Transm (Vienna). 2017;124(6):695-708. PubMed PMID: 28470423.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rat brain glucose transporter-2, insulin receptor and glial expression are acute targets of intracerebroventricular streptozotocin: risk factors for sporadic Alzheimer's disease? AU - Knezovic,A, AU - Loncar,A, AU - Homolak,J, AU - Smailovic,U, AU - Osmanovic Barilar,J, AU - Ganoci,L, AU - Bozina,N, AU - Riederer,P, AU - Salkovic-Petrisic,Melita, Y1 - 2017/05/03/ PY - 2016/11/25/received PY - 2017/04/18/accepted PY - 2017/5/5/pubmed PY - 2018/3/21/medline PY - 2017/5/5/entrez KW - Alzheimer’s disease KW - Glucose transporter 2 KW - Insulin receptor KW - Streptozotocin SP - 695 EP - 708 JF - Journal of neural transmission (Vienna, Austria : 1996) JO - J Neural Transm (Vienna) VL - 124 IS - 6 N2 - 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. SN - 1435-1463 UR - https://www.unboundmedicine.com/medline/citation/28470423/Rat_brain_glucose_transporter_2_insulin_receptor_and_glial_expression_are_acute_targets_of_intracerebroventricular_streptozotocin:_risk_factors_for_sporadic_Alzheimer's_disease L2 - https://doi.org/10.1007/s00702-017-1727-6 DB - PRIME DP - Unbound Medicine ER -