Mitochondria are critical for BDNF-mediated synaptic and vascular plasticity of hippocampus following repeated electroconvulsive seizures

Abstract

Background Electroconvulsive therapy is a fast-acting and efficient treatment of depression used in the clinic. The underlying mechanism of its therapeutic effect is still unclear. However, recovery of synaptic connections and synaptic remodeling is thought to play a critical role for the clinical efficacy obtained from a rapid antidepressant response. Here, we investigated the relationship between synaptic changes and concomitant nonneuronal changes in microvasculature and mitochondria and its relationship to brain-derived neurotrophic factor level changes after repeated electroconvulsive seizures, an animal model of electroconvulsive therapy. Methods Electroconvulsive seizures or sham treatment was given daily for 10 days to rats displaying a genetically driven phenotype modelling clinical depression: the Flinders Sensitive and Resistant Line rats. Stereological principles were employed to quantify numbers of synapses and mitochondria, and the length of microvessels in the hippocampus. The brain-derived neurotrophic factor protein levels were quantified with immunohistochemistry. Results In untreated controls, a lower number of synapses and mitochondria was accompanied by shorter microvessels of the hippocampus in "depressive" phenotype (Flinders Sensitive Line) compared with the "nondepressed" phenotype (Flinders Resistant Line). Electroconvulsive seizure administration significantly increased the number of synapses and mitochondria, and length of microvessels both in Flinders Sensitive Line-electroconvulsive seizures and Flinders Resistant Line-electroconvulsive seizures rats. In addition, the amount of brain-derived neurotrophic factor protein was significantly increased in Flinders Sensitive Line and Flinders Resistant Line rats after electroconvulsive seizures. Furthermore, there was a significant positive correlation between brain-derived neurotrophic factor level and mitochondria/synapses. Conclusion Our results indicate that rapid and efficient therapeutic effect of electroconvulsive seizures may be related to synaptic plasticity, accompanied by brain-derived neurotrophic factor protein level elevation and mitochondrial and vascular support