Naslov
Chronic corticosteron treatment affect brain insulin system in rats

Autori
Osmanović-Barilar, Jelena ; Šalković-Petrišić, Melita ; Plaschke, Konstanze ; Riederer, Peter

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Periodicum biologorum / - Zagreb, 2010

Skup
The 6th Croatian Congress of Pharmacology with International Participation

Mjesto i datum
Opatija, Hrvatska, 15.09.2010. - 18.09.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
corticosteron; insulin; learning and memory

Sažetak
Introduction Hypercortisolemia has been shown to compromise the function of the insulin receptor (IR) system in the brain and its being recognized as a risk factor for sAD. On the other hand, recent data indicate that sAD is associated with brain insulin deficiency and an insulin resistant brain state. Interaction between the insulin / IR and glucocorticoids has been suggested based on the reports of cortisol acting as the inhibitor of the IR tyrosine kinase activity which consequently lead to IR signaling dysfunction. So we aimed this study to investigate whether a long-lasting treatment with exogenous corticosterone treatment induces changes in rat behavior and in gene expression of rat brain insulin signaling pathway. Materials and methods Two groups of male adult Wister rats were treated with daily subcutaneous injection of CTS (26.8 mg/kg) or vehicle-sesame oil for 60 days while the third group was untreated control. We measured plasma CST, and psychometric investigations were conducted using a rat holeboard test system before and after the treatment. Gene expression analyses were done by RT-PCR in cerebral cortical tissue for insulin genes 1 and 2, insulin receptor (IR), insulin degrading enzyme (IDE) and tau protein. Data were analysed by Kruscal-Wallis and Mann- Whitney U-test (p<0.05). Results Sixty day-treatment of CST daily injections induced a significant 2-fold increase in rat plasma CST concentration in comparison to untreated controls. Significantly reduced behavioral abilities in CST-treated rats were associated with reduced gene expression of insulin 1 (-20%), IDE (-23%), IR (-26%) indicating an insulin resistant brain state followed by increased tau protein (+28%) gene expression. Conclusion Our results shows that chronic CST-treatment affects gene expression of the brain IR signaling cascade and increases tau gene expression associated with reductions in rats’ cognitions capacities. Therefore, exogenous glucocorticoid- mediated changes can be regarded as a major risk factor inducing brain insulin signaling disturbance thus generating abnormalities in brain metabolism and behavior indicative for sAD. Supported by Croatian MZOS and DAAD.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA