Effects of gut microbiota disturbance induced in early life on the expression of extrasynaptic GABA-A receptor α5 and δ subunits in the hippocampus of adult rats

Previous studies have demonstrated that gut microbiota disturbance significantly increases the risk of emotional disorders via the gut-brain axis, but the mechanism is unclear. Furthermore, gamma-aminobutyric acid (GABA) deficits were reported to be implicated in the development of depression and amnesia, but the alterations in the GABA-A receptor subunits that are involved in the pathogenetic process have not been fully elucidated. This study used juvenile rats that were fed ampicillin-Na to establish degree III dysbiosis of the intestinal flora and examined emotional change via the tail suspension test, forced swim test and Morris water maze. Additionally, our study investigated the expression of GABA-A receptor alpha 5 and delta subunits in the hippocampus in adulthood via q-PCR and immunohistochemistry. We focused on the role of GABA-A receptor alpha 5 and delta subunit changes induced by juvenile gut microbiota disturbance in the pathogenesis of emotional disorders in adulthood. In addition, we investigated the protective effects of probiotics and benzodiazepine (clonazepam). Findings showed that juvenile gut microbiota disturbances induced chronic depression and memory loss and reduced the expression of GABA-A receptor alpha 5 and delta subunits in the hippocampus of the adult rat. Furthermore, moderate probiotic administration led to a significant improvement compared to short-term BZ treatment. However, we are aware that these results have been established with a single animal experiment and will require further confirmation with a larger group of individuals. Future directions for the exploration of the effects of gut microbiota disturbance on GABA-A receptor alpha 5 and delta subunits are discussed.