Der Einfluss von starvationsbedingtem Östrogenmangel und Östrogensubstitution auf Gehirn-Plastizität und Verhalten bei der Ratte - eine translationale Perspektive für die Behandlung der adoleszenten Anorexia nervosa

The third most common chronic disease in young adulthood and adolescence is Anorexia nervosa (AN). Severe brain volume reductions of grey and white matter were shown in patients with AN and are connected to neuropsychological deficits and prognosis. Until now the underlying pathophysiology of this brain volume loss is unclear. Memory functions partially depend on 17β-estradiol (E2) activity. Both, memory and E2 plasma levels, are affected in patients with AN. The activity-based anorexia rat paradigm (ABA) was implemented and modified in our study. We used a 25 % starvation model in 4 weeks old animals, thus modelling chronic AN. Furthermore, we confirmed in these animals an increase in running activity and a complete loss of the estrous cycle, typical symptoms of patients with AN. For the first time, we could show that the volumes of the cerebral cortex and corpus callosum in ABA were reduced which mirrors reductions in patients with AN. These alterations were associated with a reduction of GFAP-positive astrocytes and astrocyte cell surface area as well as GFAP mRNA-expression in cerebral cortex and corpus callosum. No alterations in neuron, oligodendrocyte and microglia cell numbers were seen. Decreased E2 plasma levels and impaired object recognition memory in ABA animals were found compared to the control group. Moreover, the E2 reduction also correlated positively with the impairment of recognition memory. An E2-substitution lasting two weeks showed a trend to an increase of cerebral cortex volume reduction and E2 also significantly diminished the reduction of GFAP covered cell surface area. Our modified ABA model thus seems well suited to analyze the consequences of chronic AN on underlying behavioral, hormonal and brain pathobiology. Clinical studies are required to confirm the efficacy of E2 in the treatment of AN. Since astroglia represents the main target cell population for E2 due to high expression of various E2 receptors on astrocytes, we postulate that positive E2 effects could be the result of E2 and astroglia interactions. Our findings regarding astrocyte cell alterations could lead to new targets in the treatment of AN patients