Probiotic treatment restores normal developmental trajectories of fear memory retention in maternally separated infant rats

Abstract

Early life stress (ELS) can affect brain development and increase lifetime prevalence of psychiatric illnesses. However, the effective therapeutic interventions to ameliorate the deleterious effects of ELS have not yet been well established. Here, we confirmed that maternal separation (MS) for 3 h daily between postnatal days 2–14, a frequently used experimental model of ELS, resulted in early expression of adult-like fear memory retention in male infant rats. Administration of a probiotic formulation, Lacidofil® (95% Lactobacillus rhamnosus R0011 and 5% Lactobacillus helveticus R0052), during the separation period, prevented the precocious transition to adult-like fear memory retention in MS infant rats. Consonant with this effect, probiotic treatment also ameliorated the MS-induced increases in anxiety-like behavior as measured by the elevated plus maze and the light-dark box tests. In addition, probiotic treatment reduced MS-induced increases in neuronal activation and brain-derived neurotrophic factor protein levels in the basolateral nucleus of amygdala (BLA) after auditory fear conditioning. Furthermore, we found that probiotic treatment significantly rescued the heightened hypothalamic-pituitary-adrenal (HPA) axis response to restraint stress in MS infant rats. Taken together, these findings suggest that probiotics can restore normal developmental trajectories of fear memory retention in MS infant rats, at least in part by normalizing HPA axis abnormalities, and that the BLA serves as a critical node to mediate these interventions. Thus, we offer a potential therapeutic intervention to protect children against the harmful effects of ELS.