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 (STZicv) 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. Paraffinembedded 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 timedependent 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.

Alzheimer’s disease; Streptozotocin; Amyloid protein; Tau protein; Lysosomes; Cognitive decline

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