Translational neuroscience of anorexia nervosa: A genetic and environmental interplay underlying behavioural hyperactivity in mice

摘要: Anorexia Nervosa is a severe mental illness, affecting young females more than males. nervosa runs chronic, relapsing course and associated with high disability mortality rates. The hallmark of the disease keeping low body weight, less 85% what expected. etiology anorexia complex (unknown), risks involving environmental, temperamental, developmental genetic factors. Though not specified in diagnosis criteria, excessive physical activity has also been described as prominent feature disorder. It plays significant role development, maintenance recovery rate This thesis aims at unraveling environmental factors hyperactivity behavior susceptibility to based (ABA) model, which models this rodents. Rodent studies take place under controlled conditions, where dissection phenotypes facilitated. In we report on following novel findings. Physical levels prior restriction phase were found highly predict across set eleven inbred mouse strains exposed ABA model. Mapping behavior, by screening chromosome substitution (CS) panel, generated from C7BL/6J A/J mice, shown potential quantitative trait loci (QTL) chromosomes 4, 12 13. Further analysis revealed locus proximal region 12, however, additional research needed search for candidate genes within QTL interval that contribute observed phenotype. Early life events (inter- intra- strain cross-fostering experiments mice) able modulate background susceptible CS 4. Change maternal environment, was differences DNA methylation when compared mice raised their own biological mothers. Several implicated different psychiatric disorders, such Cntnap2, showed hypermethylated regions related reduced cross-fostering. Thus, early may adult maladaptive via epigenetic modifications. Altogether, suggest trajectory likely defined an ongoing gene environment interplay starting stage. Close onset exercise or risk factor becomes it should be considered illness severity. These results warrant further investigate modifications brain structures i.e. neuronal organizations or/and connections, have occurred how these dynamic changes affect mal-adaptive behavior.