Compound B vitamins mitigate post-traumatic stress disorder-like behaviors induced by single prolonged stress in rats by inhibiting hippocampal mitochondrial DNA methylation

Abstract

Background

Post-traumatic stress disorder (PTSD) is a serious mental disorder. Current treatments, typically using serotonin reuptake inhibitors, have limited effectiveness and often cause severe adverse effects. In the present study, we investigated whether Compound B vitamins (VBco) have protective effects in improving PTSD-like behaviors and the possible related molecular mechanisms in a rat model of single prolonged stress (SPS).

Methods

Eighty adult male rats were randomly divided into four groups (n = 20): control (CTRL), SPS, VBco control (CTRL-VBco), and SPS and VBco (SPS-VBco). After modeling, behavioral tests (including open field test, forced swimming test, sucrose preference test, fear conditioning test) were conducted. Blood was collected to detect plasma homocysteine (Hcy) concentrations. Brain tissue was collected for mitochondrial function analysis, western blotting, and quantitative real-time Polymerase Chain Reaction (PCR).

Results

VBco reduced plasma Hcy levels significantly 1 week post-SPS. The SPS-VBco group showed decreased grooming times and increased movement speed in the open field test, less resting time in the forced swim test, increased sucrose preference ratios in the sucrose preference test, and less freezing time in the fear conditioning test. VBco increased the expression of mRNA for subunits of respiratory chain-related protein in hippocampal mitochondria and improved mitochondrial complex I and IV activity and membrane potential in hippocampus. VBco reversed SPS-induced mtND1 and mtND3 methylation in hippocampal mitochondria. VBco downregulated the levels of methyltransferases (DNMT1, DNMT3A, DNMT3B) in hippocampal mitochondria.

Conclusion

VBco can inhibit hippocampal mitochondrial DNA methylation effectively. This may be one of the mechanisms by which it attenuates PTSD-like behaviors.