Potential neuroprotective effects of dehydroepiandsterone (DHEA) and its sulphate (DHEAS) in brain injury model

Neurosteroid dehidroepiandrosteron (DHEA) ključan je u modulaciji neurogeneze, metabolizma neurona i njihovog preživljenja, a uključen je i u regulaciju važnih moždanih funkcija poput neuralne plastičnosti, učenja, pamćenja i ponašanja. Dosadašnja istraživanja pokazala su da DHEA i njegov sulfat (DHEAS) ublažavaju posljedice ekscitotoksičnosti i oštećenja prouzrokovanih oksidativnim stresom te imaju potencijalno protektivno djelovanje u slučaju ishemijske ozljede mozga. Deprivacija glukoze, smanjen protok krvi te hipometabolizam glukoze povezuju se s degeneracijom i smrti neurona kod ishemijskog moždanog udara, ali i kod neurodegenerativnih bolesti kao što su Alzheimerova te Parkinsonova bolest. Sve navedeno upućuje na to da bi DHEA i DHEAS mogli biti obećavajući kandidati za istraživanja usmjerena prema zaštiti neurona, odnosno prema smanjenju oštećenja i odumiranja neurona koji prate različita akutna stanja, kronične neurodegenerativne bolesti te normalno starenje. Cilj ovog diplomskog rada je istražiti i razjasniti potencijalne učinke neurosteroida DHEA i DHEAS u prevenciji neuronske smrti i promicanju preživljavanja neurona uporabom in vitro pristupa, odnosno uporabom modela deprivacije kisika i glukoze, te reperfuzije (OGD/R) koji vrlo dobro oponaša ishemijske uvjete i s tim povezana patološka stanja. Rezultati istraživanja upućuju na to da ispitivani neurosteroidi imaju potencijal u liječenju i prevenciji ozljeda izazvanih ishemijom, kao i onih uzrokovanih neurodegeneracijom.The neurosteroid dehydroepiandrosterone (DHEA) is crucial in modulating neurogenesis, neuronal metabolism, and survival, and is involved in the regulation of important brain functions such as neural plasticity, learning, memory, and behavior. Previous research has shown that DHEA and its sulfate (DHEAS) alleviate the effects of excitotoxicity and damage caused by oxidative stress and have potentially protective effects in the case of ischemic brain injury. Glucose deprivation, decreased blood flow and glucose hypometabolism are associated with degeneration and death of neurons in ischemic stroke, but also in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. All of the above suggests that DHEA and DHEAS could be promising candidates for research aimed at protecting neurons, i.e. reducing the damage and death of neurons that accompany various acute conditions, chronic neurodegenerative diseases and normal aging. The aim of this thesis is to investigate and clarify the potential effects of the neurosteroid DHEA and DHEAS in preventing neuronal death and promoting neuronal survival using an in vitro approach, i.e. using a model of oxygen and glucose deprivation and reperfusion (OGD/R) that mimics very well ischemic conditions and related pathological conditions. Pretreatment and posttreatment with DHEA (S) proved to be neuroprotective. The results of the study suggest that the studied neurosteroids have potential in the treatment and prevention of injuries caused by ischemia, as well as those caused by neurodegeneration