аЯрЁБс>ўџ 35ўџџџ2џџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџьЅСo@№Пєbjbj p p 4"oom џџџџџџˆ|||||||, MЖDDDDDDDDœžžžžžž$RUzТE|DDDDDТ||DDLLLDР|D|DœLDœL(Lt||tD8 АТШœ)Ц4tœ0MtЯ8 Яt||||Я|t(DDLDDDDDТТDдDB дBackground. Streptozotocin-intracerebroventricularly (STZ-icv) treated rats have been proposed as an experimental model of sporadic type of Alzheimer’s disease (sAD). Decreased brain glucose/energy metabolism and cognitive deficits, similar to those observed in human sAD, have been reported in this experimental model. Changes have been generally investigated within one month following the STZ-icv treatment, with brain insulin receptor (IR) signalling and beta amyloid related changes being poorly explored. Objective. We have investigated behavioral, neurochemical, and structural changes in the brain of STZ-icv d"3 mg/kg) rats, measured one and three months following the STZ-icv treatement. Methods. Cognitive functions were tested in Morris Water Maze Swimming Test, neurochemical changes of enzymes/substrates of IR signalling cascade, like protein kinase B/Akt (Akt/PKB), phosphorylated/non-phosphorylated glycogen synthase kinase 3Б/В (pGSK 3Б/В / GSK 3Б/В) and tau protein were investigated by Western blot analysis, and beta amyloid aggregates were visualized by Congo red staining and green autofluorescence in cross-polarized light. Results. STZ-icv treated rats demonstrated significant cognitive deficits in learning and memory function in comparison to the control group, that were more pronounced after three (-46%) than one month (-33%) after the drug icv treatment. Time dependent changes of the expression of enzymes downstream the IR signalling cascade were found at the level of Akt/PKB and the pGSK   6:JKLV_e{ЁЄЈБа > @ Ч ш э ў џ    < P R V r „  И ф p r ‚ Ъ  X  Рє*\dv–адмц0,ѓычрчрчрмрмрмрмрчрмрчмчмчдЯрчрчрчрчрчрчдчФМчГ­Ѓ­ФМФМФМФМчЁчМчUhєl†h2№5aJ h2№aJhv<йh2№aJh2№B*phhІK0h2№B*ph h2№5hєl†h2№5hfUm hІK0h2№h2№h2№mHsHhєl†h2№5mHsH=ђєњјgd2№є§3Б/В / GSK 3Б/В ration, both being mildly but significantly decreased (-9%) in the hippocampus three but not one month following the STZ-icv treatment. Total tau protein expression was significantly increased in the hippocampus of STZ-icv treated rats, being more pronounced three (~170%) than one (~40%) months following the STZ-icv treatment, in comparison to the respective controls. All neurochemical changes were region specific, as a different patter was found in the frontal cortex. Histological examination revealed diffuse congophilic deposits in the brain blood vessels of STZ-icv treated rats three months following the drug treatment. Conclusion. Results strongly support the hypothesis of STZ-icv rat being a representative experimental model of the human sAD, with the potential of follow up the time course of changes at the behavioural, neurochemical and structural level. ,02Dжш l†$&ђєљятятяйгйгЩТгЗh2№hЂ2mH sH  h2№5aJhєl†h2№5aJ h2№aJhv<йh2№aJhv<йh2№B*aJphh2№B*aJph hЌ3Ѓh2№21h:p2№А‚. 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