Hipofízis adenilát-cikláz aktiváló polipeptid génhiányos egerek stresszadaptációs rendszereinek vizsgálata akut és krónikus modellekben

Abstract

János Selye defined the classic concept of stress as a „nonspecific response of the body to any threatening demand” (1936). More recently, McEwen (2000) defined stress as a real or interpreted threat to the physiological or psychological integrity on an individual that results in physiological and/or behavioral responses”. The prevalence of mood disorders in the western type of communities is continuously increasing: major depression is now the most common reason for chronic disability causing significant social and financial load on the healthcare systems (WHO, 2016). The complex neurobiological and neurochemical background of depression is not fully understood. Despite the fact that multiple groups of medicines are available for the treatment, there are patients who do not respond to the pharmacotherapy. Additionally, due to the wide range of side effects sometimes it is not possible to introduce the optimal therapeutic strategy. Therefore, to find more effective therapeutical strategies it is essential to deeper understand the pathophysiological background of the psychopathology. To reach this purpose the identification of new key mediators and drug targets is required. This may be possible if the imperative need for new well characterized and more reliable animal models will be fulfilled. Numerous groups neuropeptides and their receptors have been found to exert a tonic regulatory role in stress adaptation-response both in animals and humans. Clinical trials have been lunched to test if newly designed pharmacological agents targeted to the neuropeptide receptors may be applied as useful tools in the management of depression. (Lin 2012, Kormos and Gaszner 2013, Catena-Dell’Osso at al., 2013). The main goal of my PhD research program was to examine the stress adaptation systems in acute and chronic mouse models with the hope that our new findings may contribute to gain deeper insight into the neurobiological background of depression and may help to identify new therapeutical approaches.