Mechanisms of microbial-gut-brain axis modulation by electroconvulsive therapy in the treatment of depression
摘要
The present study aims to evaluate the effects of electroconvulsive therapy (ECT) on depressive behaviors. In addition, we explore mechanisms by which ECT alters the composition and functioning of gut microbiota through the microbiota-gut-brain axis.
MethodsA depression model in mice was established using chronic unpredictable mild stress. The mice were divided into three groups: control, depression, and ECT-treated. Depressive behaviors were assessed through a series of behavioral tests, including monitoring body weight, open field tests, sucrose preference and forced swim tests. Histological and microcirculatory assessments of brain and gut tissues were conducted using hematoxylin and eosin (H&E) staining, Nissl staining and immunofluorescence methodology along with laser speckle contrast imaging. In addition, the inflammatory cytokines Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6) and Interleukin-1β (IL-1β) were quantified in gut tissues using enzyme-linked immunosorbent assay. Metagenomic sequencing was employed to evaluate the diversity and abundance of the gut microbiota.
ResultsECT significantly improved depressive behaviors in mice as evidenced by increased body weight and decreased immobility time in the forced swim tests. H&E staining indicated a substantial reduction in gut inflammation while Nissl staining revealed a restoration of neuronal morphology following ECT treatment. Furthermore, immunofluorescence analysis showed elevated c-Fos expression in the hippocampal region (P < 0.05). Assessments of inflammatory cytokines demonstrated significant reductions in TNF-α, IL-6, and IL-1β levels in the ECT group. In addition, metagenomic sequencing showed that ECT enhanced gut microbiota diversity, particularly restoring the abundance of Bacteroides and Verrucomicrobia (P < 0.05).
ConclusionECT exerts its antidepressant effects by modulating gut microbiota and enhancing the functionality of the gut-brain axis.