engleski

Correlation between astroglial changes, cognitive and cholinergic deficit in a rat model of sporadic Alzheimer's disease: long-term follow up

INTRODUCTION Sporadic Alzheimer’s disease (sAD) is associated with cognitive and cholinergic deficit and astrogliosis in addition to the amyloid and tau protein pathology, development of which is difficult to track in humans. Central administration of streptozotocin (STZ-icv) is shown to induce also these Alzheimer-like changes due to the STZ-icv rat model has been recently proposed as a non-transgenic sAD animal model. We aimed to characterize the STZ-icv dose- and post- treatment time-dependency of cognitive and cholinergic deficit and astrogliosis in the brain of the STZ-icv rat model. MATERIALS AND METHODS Adult Male Wistar rats were given STZ- (0.3, 1 and 3 mg/kg) or vehicle-icv (controls) and sacrificed one, three, six and nine months after the treatment. Cognitive functions were measured by Passive Avoidance Test (PA) before sacrifice. Acetylcholinesterase (AChE) activity was measured in hippocampus (HPC) by Ellman’s method.Paraffin-embedded brain sections were immunohistochemically stained with glial fibrillary acidic protein (GFAP) and analysed with cellSense Dimenson software.Data were analysed by Kruskal-Wallis and Mann-Whitney U test (p<0.05). RESULTS STZ-icv rats exhibit significant dose- and time-dependent cognitive decline in PA test, emphasized with higher doses (-45% to -90%). AChE activity in the STZ-icv(3 mg/kg) treated rats was significantly elevated in HPC after one (+20%) and nine (+32%) months. Higher STZ doses increased (+35 to +45%) the expression of GFAP positive cells in HPC one and nine months following STZ administration compared to the controls. Six months after the STZ-icv treatment GFAP expression was found decreased in STZ animals. DISCUSSION Results suggest that cognitive deficit induced by higher STZ-icv doses, tend to correlate with the appearance of hippocampalastrogliosis and cholinergic deficitin the STZ-icv rat model. Found changes follow similar biphasic pattern which starts with acute changes found 1 moth after the treatment (acute response), followed by normalization and thenprogressive deterioration found 6-9 months after the treatment (chronic response). Acknowledgements: Supported by UKF and MZOS (108-1080003-0020).

sporadic Alzheimer’s disease; intracerebroventricularstreptozotocin; memory; astrogliosis; cholinergic transmission

nije evidentirano