engleski

Metabolic response to central streptozotocin application in a rat model of sporadic Alzheimer's disease

Introduction Glucose is the main source of energy in the periphery and brain and insulin plays a major role in its homeostasis. Recently, insulin resistant brain state has been found in streptozotocin (STZ)-intracerebroventricularly (icv) treated rats, which represent an experimental model of sporadic Alzheimer’s disease (sAD). Methods Adult male Wistar rats were injected icv with three STZ doses (0.3-3 mg/kg) or vehicle only (controls) and sacrificed one week and three months after the treatment. Cognitive functions were tested by Passive Avoidance (PA) Test before sacrifice. Plasma glucose concentrations were measured by glucose oxidase method (Glucose-PAP Test). IR mRNA expression in hippocampus (HPC) was measured by RT-PCR (3 mg/kg STZ-icv dose). Data were analysed by Kruskal-Wallis and Mann-Whitney U test (p<0.05). Results Cognitive functions, unaltered after one week, were significantly decreased in STZ-icv treated rats with 1 and 3 mg dose three months after the treatment (-46.67% and -66.79%, respectively). Blood glucose concentration was mildly increased with 1 and 3 mg STZ dose one week after the STZ- icv treatment (+14.76% and +17.90%, respectively) and normalised three months afterwards. IR mRNA expression in HPC was significantly increased early after the STZ-icv treatment (+39.83%) but declined to -19.23% three months after the treatment. Conclusion Results show the possible dose-dependent acute metabolic response to STZ-icv treatment seen both peripherally (blood glucose increment) and centrally (HPC-IR mRNA increment), while eventually, the consequences of STZ-icv treatment are manifested at the central level only, impairing also the memory. Acknowledgement Supported by UKF, DAAD and MZOS (108-1080003- 0020).

streptozotocin; insulin receptor; glucose

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