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Jens Randel Nyengaard

Mitochondria are critical for BDNF-mediated Synaptic and Vascular plasticity of Hippocampus following Repeated Electroconvulsive Seizures

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Background: Electroconvulsive therapy (ECT) 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 non-neuronal changes in microvasculature and mitochondria, and it relationship to Brain-derived neurotrophic factor (BDNF) level changes after repeated electroconvulsive seizures (ECS), an animal model of ECT.

Methods: ECS 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 (FSL/FRL) rats. Stereological principles were employed to quantify numbers of synapses and mitochondria, and the length of microvessels in the hippocampus. The BDNF protein levels were quantified with immunohistochemistry.

Results: In untreated controls, a lower number of synapses and mitochondria were accompanied by shorter microvessels of the hippocampus in "depressive" phenotype (FSL) compared to the "non-depressed" phenotype (FRL). ECS administration significantly increased the number of synapses and mitochondria, and length of microvessels both in FSL-ECS and FRL-ECS rats. In addition, the amount of BDNF protein was significantly increased in FSL and FRL rats after ECS. Furthermore, there was a significant positive correlation between BDNF level and mitochondria/synapses.

Conclusion: Our results indicate that rapid and efficient therapeutic effect of ECS may be related to synaptic plasticity, accompanied by BDNF protein level elevation, mitochondrial and vascular support.

Original languageEnglish
JournalInternational Journal of Neuropsychopharmacology
Pages (from-to)291-304
Number of pages14
Publication statusPublished - 1 Mar 2018

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