Uticaj hiperaktivnosti osovine hipotalamus-hipofiza-nadbubrežna žlezda i oksidativnog stresa na učenje i pamćenje: modulatorna uloga suplementacije magnezijumom
Effects of hyperactivity of the hypothalamic-pituitary-adrenal axis and oxidative stress on learning and memory: modulatory role of magnesium supplementation
Докторанд
Đurić, VedranaМентор
Stanić, DušankaЧланови комисије
Petrović, JelenaStarčević, Ana
Pejušković, Bojana
Метаподаци
Приказ свих података о дисертацијиСажетак
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 i...mprovement. 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.