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Correlation of structural and cognitive changes with insulin resistance in the brain of a rat model of sporadic Alzheimer's disease (CROSBI ID 634225)

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Knezovic, Ana ; Osmanovic-Barilar, Jelena ; Salkovic-Petrisic, Melita Correlation of structural and cognitive changes with insulin resistance in the brain of a rat model of sporadic Alzheimer's disease. 2015

Podaci o odgovornosti

Knezovic, Ana ; Osmanovic-Barilar, Jelena ; Salkovic-Petrisic, Melita

engleski

Correlation of structural and cognitive changes with insulin resistance in the brain of a rat model of sporadic Alzheimer's disease

INTRODUCTION The ethiopathogenesis of sporadic Alzheimer’s disease (sAD) in humans is unknown and pathology onset and development can only be investigated in well characterized and validated representative animal sAD model. Central administration of streptozotocin (STZ- icv) is shown to induce many of AD-like changes in rodents and STZ-icv rat model has been proposed as a non-transgenic sAD animal model. We aimed to characterize dose- and post- treatment time-dependency of cognitive deficit, structural changes and insulin resistance in the brain of a 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 1 and 2 weeks and 1, 3, 6 and 9 months after the treatment. Cognitive functions were measured by Passive Avoidance (PA) and Morris Water Maze (MWM) tests before sacrifice. Insulin receptor (IR) mRNA expression was measured by RT-PCR and protein expression of glycogen synthase kinase 3 (GSK3) and tau protein by Western blot in hippocampus. Histology data obtained by Bielschowsky silver and Nissl staining were analysed with cellSense Dimenson software. Kruskal-Wallis and Mann- Whitney U test (p<0.05) were used for statistical analysis. RESULTS STZ-icv rats exhibited significant dose- and time-dependent biphasic cognitive decline in PA and MWM tests, emphasized with higher doses. Morphological changes (corpus callosum thinning and expansion of lateral ventricles) showed dose- and time-dependent slow development and progression most pronounced with the highest dose 9 months after the STZ-icv treatment. Acute upregulation of IR mRNA expression was followed by a long-term persistent downregulation that started 3 months after the treatment while increment in GSK3 activity and tau hyperphosphorylation followed a biphasic pattern. DISCUSSION Results suggest that high dose-induced cognitive decline correlate well with dysfunctional signalling downstream IR cascade in STZ-icv rat model, all following the biphasic pattern of changes: acute response which can be partially/totally normalised, and pathology worsening/reappearance as a long-term chronic response. This chronic neurochemical/cognitive response correlates well with manifestation of structural deterioration of the brain which develops slowly. The late phase in STZ-icv rat pathology is more representative for mimicking human sAD condition.

sporadic Alzheimer’s disease; intracerebroventricular; streptozotocin; memory; insulin resistance; corpus callosum

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o prilogu

2015.

objavljeno

Podaci o matičnoj publikaciji

Podaci o skupu

5.Hrvatski kongres neuroznanosti

poster

17.09.2015-19.09.2015

Split, Hrvatska

Povezanost rada

Temeljne medicinske znanosti