SPLEEN MICROBIOTA-BEHAVIOUR-NEUROGENESIS ASSOCIATIONS IN A SINGLE PROLONGED STRESS MODEL OF PTSD: EFFECT OF ARIPIPRAZOLE

Post-traumatic stress disorder (PTSD) develops following severe trauma and is associated with alterations in neurogenesis and the gut microbiota. Aripiprazole (ARI), an atypical antipsychotic used in PTSD treatment, influences neurogenesis and gut microbial composition. This study investigated the effects of a 28-day ARI treatment on anxiety-like behaviour, hippocampal neurogenesis, spleen bacterial composition, and their interactions in the single prolonged stress (SPS) animal model of PTSD.
Anxiety-like behaviour was assessed using the elevated plus maze (EPM). Expression of selected neurogenic markers in the dorsal and ventral hippocampus and bacterial 16S rRNA in the spleen were analysed using RT-PCR.
SPS exposure induced anxiety-like behaviour in the EPM, however, ARI treatment did not reverse this effect. Notably, time spent in the open arms (OA) of the EPM positively correlated with Firmicutes and Actinobacteria 16S rRNA levels, while the number of OA entries correlated with Bacteroidetes 16S rRNA. In the spleen, SPS and SPS+ARI reduced Bacteroidetes expression, whereas Actinobacteria expression increased in the SPS+ARI group compared to SPS. SPS increased γ/δ-Proteobacteria and Lactobacillus 16S rRNA levels, an effect attenuated by ARI. No significant changes in neurogenic marker mRNA levels were observed in the dorsal or ventral hippocampus following SPS/SPS+ARI exposure. However, GFAP and DCX mRNA levels correlated with spleen Enterobacteria and γ/δ-Proteobacteria expression.
These findings demonstrate that SPS alters spleen bacterial abundance, with specific bacterial changes associated with anxiety-like behaviour and neurogenic markers, underscoring the relevance of the gut-spleen-brain axis in PTSD pathology.
This work was supported by APVV-24-0213 and APP0749.