Uticaj hiperaktivnosti osovine hipotalamus-hipofiza-nadbubrežna žlezda i oksidativnog stresa na učenje i pamćenje: modulatorna uloga suplementacije magnezijumom

Abstract

Hronični stres, neadekvatan način ishrane kao i oksidativni stres mogu se dovesti u vezu sa kognitivnim poremećajima i poremećajima ponašanja. Za Mg je pokazano da smanjuje hiperaktivnost stres osovine hipotalamus-hipofiza-nadbubrežna žlezda, a uključen je i u regulaciju ekscitatorne sinaptičke transmisije, sinaptičke plastičnosti i neurogeneze putem modulacije aktivnosti NMDA receptora u mozgu. Cilj istraživanja doktorske disertacije bio je da se ispita uticaj hiperaktivnosti stres osovine, izazvane primenom ACTH, na učenje i pamćenje, parametre neurogeneze i parametre oksidativnog stresa Wistar pacova. Takođe, cilj je bio da se ispita modulatorni efekat akutne i dugoročne (300 mg Mg/L, 28 dana) primene Mg kod Wistar pacova u fiziološkim i uslovima hiperaktivnosti HPA osovine. Rezultati istraživanja ukazuju da suplementacija Mg pokazuje pozitivan efekat na memoriju i stimulatorni efekat na proces adultne neurogeneze u hipokampusu eksperimentalnih životinja, dok tretmani ACTH hormonom nisu doveli do poboljšanja memorije. Naime, hiperaktivnost HPA osovine negativno je modulisala proces neurogeneze u hipokampusu, povećala osetljivost DNK molekula na ex-vivo izazvana oksidativna oštećenja i povećala oksidativni stres u plazmi Wistar pacova. Mg je suprimirao hiperaktivnost HPA osovine smanjenjem nivoa kortikosterona i vraćanjem balansa oksidativnog statusa, uz smanjenje osetljivosti DNK na in vitro oksidativna oštećenja. S obzirom da je u ovoj disetaciji pokazan prokognitivni i uticaj Mg na redukciju efekata farmakološki izazvanog stresa kod eksperimentalnih životinja, opravdano bi bilo ispitivanje primene Mg kod pacijenata kod kojih su prisutna kognitivna oštećenja različitog stepena povezana sa promenama u strukturi i funkciji hipokampusa i sa povećanim oksidativnim stresom.

Chronic stress, inadequate diet as well as oxidative stress can be linked with cognitive and behavioral disorders. It has been shown that Mg reduces hyperactivity of stress axis, hypothalamic-pituitary-adrenal axis, whereas it is involved in regulation of excitatory synaptic transmission, synaptic plasticity, and neurogenesis via modulation of NMDA receptor activity in brain. The aim of doctoral dissertation research was to investigate effect of stress axis hyperactivity, via ACTH application, on learning and memory, on parameters of neurogenesis and on parameters of oxidative stress in Wistar rats. Also, aim was to evaluate modulatory effect of acute and chronic (300 mg Mg/L, for 28 days) Mg supplementation in Wistar rats in physiological conditions and during HPA axis hyperactivity. The results indicate that Mg supplementation shows positive effect on memory and stimulatory effect on adult neurogenesis in hippocampus of experimental animals, while ACTH treatment did not show memory improvement. Namely, hyperactivity of HPA axis has negatively modulated neurogenesis in hippocampus, has increased DNA sensitivity to ex-vivo induced oxidative damage and has increased oxidative stress in Wister rats’ plasma. Mg has suppressed HPA axis hyperactivity via decreasing corticosterone levels and via restoring the balance of oxidative status, while decreasing DNA sensitivity to in vitro induced oxidative damage. Considering that procognitive and influence of magnesium on reduction of pharmacological induced stress effects in experimental animals has been shown in this dissertation, it would be justified further investigation of magnesium supplementation in patients with different levels of cognitive disfunction, linked with changes in structure and function of hippocampus and with increased oxidative stress.