4249 Markers of mitochondrial biogenesis, fusion and architecture are disturbed in PBMC from war veterans with posttraumatic stress disorder (PTSD)

Abstract

OBJECTIVES/GOALS: The aim of this study was to define the transcription profiles of the molecular markers of mitochondrial biogenesis and fusion/architecture, and the markers of mtDNA copy numbers in the peripheral blood mononuclear cells (PBMCs) from war veterans with/without post-traumatic stress disorder (PTSD). METHODS/STUDY POPULATION: The peripheral blood mononuclear cells (PBMCs) from war veterans with/without post-traumatic stress disorder (PTSD) were used to monitor transcription profile of the molecular markers of mitochondrial biogenesis and fusion/architecture, as well as the markers of mtDNA copy numbers. The human male immortalized monocytes were exposed in vitro to hormonal markers of PTSD in order to monitor the effects of each particular hormonal marker on the molecular markers of mitochondrial biogenesis and fusion/architecture, as well as the markers of mtDNA copy numbers. RQ-PCR analyses were used to define transcriptional profile of above mentioned markers. RESULTS/ANTICIPATED RESULTS: The transcription profiles of above mentioned markers were disturbed, with high individual variability within the groups. A significant increase in the expression of the PPARGC1A transcript was observed in a group of subjects with current PTSD, as well as in the subjects with “life-time” PTSD, compared to healthy controls. PPARGC1B, NRF2 and MFN2 transcripts increased only in PBMCs of “life-time"-PTSD, while the level of transcripts for other investigated genes and the ratio of markers of mtDNA copy numbers showed no significant difference between groups. The in vitro results showed parallelism with the results obtained using the PBMCs from the subjects of the PTSD study. DISCUSSION/SIGNIFICANCE OF IMPACT: Although preliminary (the analysis require a larger number of subjects), the results are first findings and a solid base for further extensive multidisciplinary research in order to clarify the molecular mechanisms for the prevention and treatment of trauma-induced pathological conditions.