engleski

Early changes of acetylcholinesterase activity and insulin system in the brain of the streptozotocin- intracerebroventricularly treated rat model of sporadic Alzheimer's disease

Introduction Sporadic Alzehimer’s disease (sAD) is associated with central cholinergic deficit and impaired insulin receptor (IR) signaling both in humans and its animal model, rats treated intracerebroventricularly with streptozotocin (STZ-icv) which enable assessment/follow up of alterations starting immediately after the STZ- induced brain damage. Aims We aimed to explore the acute changes of central cholinergic transmission and insulin system in the STZ-icv rats, measured 1 day, 1 and 2 weeks after the STZ-icv treatment. Methods Adult Wistar rats were administered STZ (0.3-3 mg/kg) or vehicle (controls) icv injections. IR and insulin-degrading enzyme (IDE) protein expression was measured in hippocampus (HPC) by SDS-PAGE electrophoresis and immunoblotting. Acetylcholinesterase (AChE) activity was measured in HPC and parietotemporal cortex (PTC) by Ellman’s method. Data were analysed by Mann- Whitney U test (p<0.05). Results One day after STZ-icv (1 mg/kg) administration hippocampal IR (45.34%) and IDE (30.83%) protein expression was significantly increased as well as AChE activity (26.31%) which after 1 week was normalized in HPC but significantly increased in PTC (23.37%). No clear dose-dependent effect on AChE activity was found with 0.3-3 mg/kg STZ-icv dose range. IR and IDE protein expression in HPC was normalized 2 weeks after STZ-icv (3 mg/kg) administration. Conclusion Cholinergic and insulin brain system are differently affected immediately after STZ-icv induced brain damage ; the former showing immediate but mild onset and development of cholinergic deficit and the latter demonstrating acute, stress-induced response in IR signalling which is compensated during the following two weeks. Acknowledgement Supported by UKF, MZOŠ (108-1080003-0020) and DAAD.

streptozotocin; acetylcholinesterase; sporadic Alzheimer's disease

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