Mitochondrial gene expression profiles in PTG in the amygdala of a PTSD model following corticosterone therapy.

Abstract

The metabolic and neuronal mechanisms underlying the development of posttraumatic growth (PTG) following corticosterone (CORT) therapy in patients with posttraumatic stress disorder (PTSD) are not well defined. In this study, we assess differential gene expression (DEG) profiles associated with mitochondrial function in the amygdala of a PTSD rodent model using a mitochondrial focused gene array chip for both metabolic and neuronal functions. Amygdala tissue samples were excised from four groups of rats (N = 10 each) including: non-stressed control, stressed alone, CORT therapy alone, and CORT therapy with stress. CORT plus stress took place over a three-day period. All groups were sacrificed and assessed after a total of 14 days. Total RNA was isolated, cDNA was synthesized, and gene expression levels were determined using a cDNA microarray. During the development of the anxiety symptom, equivalent to the delayed and exaggerated fear associated with PTSD, 111 DEGs were determined to be statistically significant (p < 0.01) in CORT therapy compared to non-stressed controls. 86 DEGs were determined to be statistically significantly in the CORT with stress administered group in the amygdala complex using stringent criteria (p < 0.01). Furthermore, ingenuity pathway analysis (IPA) revealed six signaling network pathways in the amygdala complex of the CORT+Stress group. As in the CORT+Stress group, the measurement of acoustic startle showed no significant difference in comparison to the control group. Thus, anxiety was mitigated, and resiliency was increased with CORT therapy. In addition, the Venn diagram analysis indicated that 55 DEGs in the stressed group had 13 DEGs independently non-effected by CORT therapy associated with neuronal signaling networks and 42 DEGs dependently effected by CORT therapy in the stressed group alone. Thus, information provided by a neuronal and metabolic gene array allowed us to determine the expression profile of mitochondrial genes in PTG associated with the amygdala complex of a rodent model of PTSD. This result provides further understanding of the metabolic and neuronal signaling mechanisms associated PTG in the development of PTSD.