engleski

Time-course of astroglial changes and cognitive decline in a rat model of sporadic Alzheimer's disease

Objectives: Cognitive decline is a major behavioural hallmark and astrogliosis is a characteristic neuropathological feature of sporadic Alzheimer's disease (sAD). Central administration of streptozotocin (STZ-icv) is shown to induce both these Alzheimer-like changes in rats due to STZ-icv rat model has been proposed as ananimal model of sAD. We have investigated the 9-month time course of cognitive decline and astrogliosis induced by 3 STZ-icv doses in this rat sAD model. Methods: Male 3 month-old Wistar rats were icv injected by STZ- (0.3, 1 and 3 mg/kg dose) or vehicle (controls) and sacrificed one, three, six or nine months after the treatment. Cognitive functions were tested by Passive Avoidance Test before sacrifice. Paraffin-embedded brain sections were immunohistochemically stained for detection of glial fibrillary acidic protein (GFAP) signal and analysed with cellSense Dimenson software. Data were analysed by Kruskal-Wallis and Mann-Whitney U test (p<0.05). Results: STZ-icv rat model demonstrated dose- and time-dependent cognitive deficits, pronounced with higher doses with acute decline after 1 month (-90%) and progressive one after 6 - 9 months (-45% to -90%). Higher STZ doses increased (+45%) the expression of GFAP positive cells acutely after 1 month, decreased (-63%) it after 6 months and then increased it (+35%) again 9 months following STZ administration. Conclusion: Results suggest that both cognitive deficit and astrogliosis induced by higher STZ-icv doses, demonstrate a biphasic pattern of appearance ; acute changes found after1 month and chronic (progressive) ones found 6-9 months after the treatment. Supported by UKF and MZOS.

astrogliosis; Alzheimer; cognition; streptozotocin

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