Maternal Separation in ABA Rats Promotes Cell Proliferation in the Dentate Gyrus of the Hippocampus

Abstract

Anorexia nervosa (AN) is a serious eating disorder characterized by self-starvation and excessive weight loss. Several studies support the idea that life stressors during the postnatal period could play a pivotal role in the pathogenesis of AN, underlying the multifactorial etiology of this disease. The activity-based anorexia (ABA) animal model mimics core features of the mental disorder, including severe food restriction, weight loss, and hyperactivity. Previous results obtained in our lab showed that maternal separation (MS) induces behavioral changes in anorexic-like ABA rats in a sexually dimorphic way: in females, the MS promoted hyperactivity and a less anxious-like phenotype in ABA animals; in males, instead, the MS attenuated the anxiolytic effect of the ABA protocol. These results led us to investigate the effect of the MS on brain areas involved in the control of the anxiety-like behavior. We focused our attention on the adult hippocampal neurogenesis, a process involved in the response to environmental stimuli and stressful condition. We analyzed the volume of the whole hippocampus and the proliferation rate in the dentate gyrus (DG) by quantifying Ki67-cells density and characterizing neuronal phenotype (DCX) and glial cells (GFAP) with double-fluorescence technique. The results obtained showed that only in maternally separated anorexic rats there is an increase of proliferation in DG, underlying the presence of a synergic effect of MS and ABA that boost the proliferation of new neurons and glia progenitors in a more evident way in females in comparison to males.

Keywords: activity-based anorexia; adult neurogenesis; maternal deprivation; sexual dimorphism.