Mitochondrial transplantation attenuates lipopolysaccharide- induced depression-like behaviors

Abstract The dysfunction of mitochondria plays important roles in the development of depression. Interestingly, increasing numbers of evidence show the therapeutic benefits of mitochondria transfer. Therefore, we hypothesized that injection of exogenous mitochondria would contribute to ameliorate depressive-like symptoms. In this study, the antidepressant-like effect of intravenous isolated mitochondria was evaluated on a lipopolysaccharide (LPS)- induced model of depression. The depressive-like behaviors were assessed using forced swim test (FST), tail suspension test (TST) and sucrose preference test. Besides, the neurogenesis, expression of brain-derived neurotrophic factor (BDNF), glial activation, neuroinflammation, oxidative stress and ATP production were determined in the hippocampus. The results showed that treatment of isolated mitochondria decreased the immobility time of mice in the FST and TST, and attenuated the decrease in sucrose preference test. Moreover, isolated mitochondria significantly reduced the activation of astrocyte and microglia as well as neuroinflammation (i.e. 1 L-1β, TNF-α and COX-2), increased BDNF expression and neurogenesis, restored the dysfunction of ATP production and oxidative stress in inflammation- induced depression. Taken together, the data suggested for the first time that injection of isolated mitochondria ameliorated LPS- induced depressive-like behaviors. The new discovery for the present study provides that mitochondrial transplantation might act as a new therapeutic strategy for MDD.