Efficacy of Probiotic Escherichia coli Nissle 1917 in Counteracting Reserpine-induced Depression-like Symptoms and Neuroinflammation in Zebrafish

Background: Depression is emerging as a significant global public health concern. Escherichia coli Nissle 1917 (EcN), a well-known probiotic, is recognized for its antioxidant and anti-inflammatory properties and has demonstrated efficacy in treating inflammatory bowel diseases and other gastrointestinal disorders. Methods: Reserpine, an obsolete antihypertensive medicine known to cause neurotoxicity, was used to induce depression-like symptoms in adult zebrafish. Our experimental approach encompassed various stages, including behavior assessment, histological examination, antioxidant assays, and enzyme-linked immunosorbent assay (ELISA). Results: Reserpine exposure resulted in significant behavioral deficits, increased oxidative stress, neuronal damage, and elevated pro-inflammatory cytokine levels in the zebrafish brain. EcN treatment significantly improved locomotor and exploratory behaviors and restored social preference compared with the reserpine group ( p < .05). EcN markedly increased antioxidant enzyme activities (Catalase and Superoxide dismutase) while reducing lactate dehydrogenase, nitric oxide, and lipid peroxidation levels ( p < .05). Furthermore, EcN significantly reduced tumor necrosis factor-α, interleukin-1β, and necrosis factor-κB levels in the brain relative to reserpine-treated fish ( p < .001). These effects were comparable, though slightly less pronounced, than those observed with Venlafaxine. Conclusions: EcN significantly attenuated reserpine-induced depression-like behavior, oxidative stress, neuronal damage, and neuroinflammation in adult zebrafish, as evidenced by statistically significant improvements in behavioral, biochemical, and inflammatory endpoints. These findings support EcN as a promising psychobiotic with antidepressant-like properties, warranting further mechanistic and translational investigations.