engleski

Time course of amyloid beta pathology in streptozotocin-rat model of sporadic Alzheimer's disease.

Objectives: Modelling of Alzheimer&#8217; s disease usually involves transgenic mice models which represent early onset familiar type of Alzheimer&#8217; s disease (AD) for which pathological assemblies of amyloid beta (A&#946; ) are thought to be the primary cause. Streptozotocin-intracerebroventricularly (STZ-icv) treated rats have been recognized as an experimental model for more frequent sporadic type of AD (sAD) which share with humans similarities of impaired brain insulin receptor (IR) signalling. We aimed to investigate the six month long time course of possible pathological changes of beta amyloid following the brain damage induced by STZ-icv treatment in rats. Methods. Male Wistar rats (3-4 month old) were sacrifice one, three or six months after STZ-icv treatment (1-3 mg/kg). Congo red staining and A&#946; 1-42 immunohistochemistry analyses were done on fixative-perfused, paraffin-embedded brain sections. Cognitive functions were tested in Morris Water Maze Test. Cruscal-Walles ANOVA and Mann-Whitney U test (P<0.05) were used. Results. One month after STZ-icv treatment no changes of A&#946; were observed, while congophilic A&#946; aggregates in meningeal capillaries which gave autoflorescence green light in cross-polarized light, and intracellular A&#946; 1-42 accumulation in hippocampus/cerebral cortex were found after three months. In these regions A&#946; 1-42 signal revealed primitive plaques formation six months following the STZ-icv treatment. Cognitive deficits, observed already after one month, persisted along the experiment. Conclusions. Results demonstrate the sequence of A&#946; pathology development starting in capillaries, moving to intracellular and finally extracellular accumulation and primitive plaque formation with the duration of period after the brain damage induced by betycytotoxic drug streptozotocin. Since STZ-icv treatment induces insulin resistant brain state (IRBS) in rats, these results provide evidence that IRBS could be a pathological core in generation of sAD preceding and triggering A&#946; plaque development and tau protein hyperphosphorylation.

Streptozotocin rat model; Sporadic Alzheimer's Disease; Beta-Amyloid

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