engleski

Cognitive training and brain insulin receptor in rat model of sporadic Alzheimer’s disease

Growing body of evidence indicates that physical and mental activities have beneficial effects on cognitive impairments in sporadic Alzheimer’s disease (sAD) but underlying mechanism is not clear. Brain insulin system dysfunction in regions involved in learning and memory has been recently reported in sAD and its experimental model, streptozotocin intracerebroventriculary (STZ-icv) treated rats. Time-dependent development of alterations in insulin receptor (IR) signaling downstream the phosphatidylinositol-3 kinase pathway resulting in tau hyperphosphorilation and amyloid beta (Aβ) angiopathy three months after STZ-icv treatment have been found. This study was aimed to investigate the effect of cognitive training on the STZ-icv induced early changes of brain IR. Adult male Wistar rats were treated with STZ-icv (1 mg/kg) while the controls received vehicle only. Half of the control and STZ-treated group was rendered to intensive 4-day long mental training in the Morris Water Maze Swimming test, two and four weeks after the drug treatment, while the other half of each group remained untrained. IR protein expression in hippocampus and temporal cortex was determined by immunoblotting 1 month after STZ-icv treatment. Data were analysed by Mann-Whitney U-test (p<0.05). Significant cognitive deficit has been found two (-36.4%) and four (-35.6%) weeks following the STZ-icv treatment. In comparison to the controls, the expression of IR protein in hippocampus was significantly decreased (121.7 ± ; 2.4 vs. 97.3 ± ; 1.5) in all STZ-icv treated animals regardless their previous training condition, while no change was found in temporal cortex between the control and STZ-icv treated rats in both trained and untrained animals. Decreased IR expression in hippocampal and unchanged in cortical tissue one month following the STZ-icv treatment suggests region-specific pattern of brain IR alterations in experimental sAD model. No difference in hippocampal IR expression between the STZ-icv trained and untrained rats in this experiment could suggest that either cognitive training longer than one month or more intensive training within 1 month is needed to induce the beneficial effect on cognitive deficits, since in AD patients this effect has been observed in follow-up studies lasting 2-9 years. Supported by Croatian MZOS (108-1080003-0020) and DAAD.

streptozotocin; sporadic Alzheimer disease; insulin receptor; brain; cognitive training

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