Radix Polygalae Extract Attenuates PTSD-like Symptoms in a Mouse Model of Single Prolonged Stress and Conditioned Fear Possibly by Reversing BAG1

ABSTRACT

Radix Polygalae (RP) has been used to relieve psychological stress in traditional oriental medicine. Recently, cell protective, antiamnestic and antidepressant-like effects were disclosed but the possible application of RP to post-traumatic stress disorder, in which exaggerated fear memory persists, has not yet been explored. For this purpose, the effects of RP on fear behavior was examined in a mouse model of single prolonged stress and conditioned fear (SPS-CF), previously shown to mimic key symptoms of post-traumatic stress disorder. Male mice received daily oral dose of RP extract or vehicle during the SPS-CF procedure. Then fear-related memory (cohort 1, n=25), non-fear-related memory (cohort 2, n=38) and concentration-dependent effects of RP on fear memory (cohort 3, n=41) were measured in 3 separate cohort of animals. Also working memory and anxiety-like behaviors were measured in cohort 1. RP-treated SPS-CF mice exhibited attenuated contextual but not cued freezing and no impairments in the working memory and spatial reference memory performances relative to vehicle-treated SPS-CF controls. RP-treated SPS-CF and naive mice also demonstrated no difference in anxiety-like behavior levels relative to vehicle-treated SPS-CF and naive controls, respectively. In the hippocampus of SPS-CF mice, expression of BAG1, which regulates the activity of GR, was decreased, whereas RP increased expression of BAG1 in naïve and SPS-CF mice. These results suggest that RP exerts some symptomatic relief in a mouse with exaggerated fear response. RP and its molecular components may thus constitute valuable research targets in the development of novel therapeutics for stress-related psychological disorders.