engleski

Acute changes of acethylcholinesterase activity and tau protein phosphorylation in mouse model of sporadic Alzheimer’s disease

Introduction: Intracerebroventricular (icv) administration of streptozotocin (STZ) generates a mouse model of sporadic Alzheimer’s disease. Long term effects of STZ-icv treatment have been well documented but the acute neurochemical impairment have not been investigated thoroughly enough. We aimed to explore acute (within 24 hours post icv injection) cholinergic and tau protein changes in STZ-icv mouse model. Materials and methods: Mice (strain C57Bl/6) were injected icv with STZ (1 and 1, 5 mg/kg) or vehicle-citrate buffer (controls). The animals were sacrificed 15 min, 1, 6 and 24 hours following the STZ-icv treatment. Acetylcholinesterase (AChE) activity in hippocampus (HPC) and parietal cortex (PC) was measured spectrophotometrically by Ellman’s method. Protein expression of phosphorylated tau protein (PHF13 and AT8) in HPC and PC was measured by SDS-PAGE electrophoresis, followed by Western blot analysis. Data were analysed by Mann-Whitney U test (p<0.05). Results: One hour after STZ-icv injection only the expression of PHF13 was found significantly increased in HPC (+26%) and PC (+37%), while the expression of AT8 was found significantly increased (+96%) in PC only. The AChE activity in PC was significantly increased 6 (+10%) and 24 hours (+15.5%) following the STZ-icv injection Conclusion: Results indicate that changes in tau phosphorylation are occurring earlier than those of AChE activity. Additionally, both changes occur earlier in PC than in the HPC, which indicates that STZ-icv administration triggers different acute post-treatment time- and brain-region dependent changes in the mouse brain.

mice; streptozotocin; cholinergic; tau

nije evidentirano