engleski

Primitive plaques are consequence of experimental brain insulin system dysfunction

Amyloid beta (Aβ ) plaques in the brain are thought of as the primary cause of all Alzheimer’ s disease (AD) forms, while other changes are considered as their consequences, including impairments in brain insulin receptor (IR) signaling. We investigated whether damage to brain IR could trigger Aβ pathology in streptozotocin-intracerebroventricularly (STZ-icv) treated rats representing experimental model of sporadic AD (sAD). Aβ 1-42 expression was visualized by immunohystochemistry and Aβ Congo red staining in brain of STZ-icv treated (1-3 mg/kg) male Wistar rats, one, three and six months following the treatment. Cognitive deficits was measured by Morris Water Maze Test and analyzed by Cruscal-Walles ANOVA and Mann-Whitney U test (P<0.05). Cognitive deficits were found already 1 month after STZ treatment and persisted afterwards. At month 1, only gene/protein changes of insulin and IR itself were found followed by mild increase in tau protein expression. At month 3 changes downstream IR signaling cascade were found followed by hyperphosphorylation of tau protein, Aβ -like aggregates in meningeal capillaries and Aβ 1-42 intracellular tissue aggregates. At months 6, Aβ 1-42 signal detected primitive plaques in STZ-icv treated rats. IR signaling cascade dysfunction preceded and induced Aβ plaque development in experimental sAD. Supported by MZOS (108-1080003-0020) and DAAD.

brain insulin ; plaques ; streptozotocin ; experimental rat model ; Alzheimer's disease

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