Abstract
The metabolic mechanisms underlying the development of exaggerated fear in post-traumatic stress disorder (PTSD) are not well defined. In the present study, alteration in the expression of genes associated with mitochondrial function in the amygdala of an animal model of PTSD was determined. Amygdala tissue samples were excised from 10 non-stressed control rats and 10 stressed rats, 14 days post-stress treatment. Total RNA was isolated, cDNA was synthesized, and gene expression levels were determined using a cDNA microarray. During the development of the exaggerated fear associated with PTSD, 48 genes were found to be significantly upregulated and 37 were significantly downregulated in the amygdala complex based on stringent criteria (p < 0.01). Ingenuity pathway analysis revealed up- or downregulation in the amygdala complex of four signaling networks – one associated with inflammatory and apoptotic pathways, one with immune mediators and metabolism, one with transcriptional factors, and one with chromatin remodeling. Thus, informatics of a neuronal gene array allowed us to determine the expression profile of mitochondrial genes in the amygdala complex of an animal model of PTSD. The result is a further understanding of the metabolic and neuronal signaling mechanisms associated with delayed and exaggerated fear.
Highlights
The neurobiology of exaggerated fear is important in understanding traumatic stress and post-traumatic stress disorder (PTSD)
We examined the relationship of altered amygdala mitochondrial-function genes and the molecular signaling pathways associated with a key symptom of PTSD: delayed and exaggerated fear
We have shown that a substantial number of up- and downregulated genes related to mitochondrial function in the amygdala are associated with an animal model of PTSD based on exaggerated startle and retardation of growth [9, 13]
Summary
The neurobiology of exaggerated fear is important in understanding traumatic stress and post-traumatic stress disorder (PTSD). Decades of animal studies have shown that the amygdala is key in the neuronal system that orchestrates the fear memory and exaggerated fear evoked by stress. Mitochondria are targets for stress hormones such as corticosterone (CORT) and are increasingly recognized as key components in stress-related mental disorders [5, 6]. The current study used a rat model of PTSD to further examine amygdala function and traumatic stress. We examined the relationship of altered amygdala mitochondrial-function genes and the molecular signaling pathways associated with a key symptom of PTSD: delayed and exaggerated fear. We screened for 1500 mitochondrial-function-associated genes, including 37 mitochondrial DNA (mtDNA)-encoded genes, 1,098 nuclear DNA (nDNA)-encoded and mitochondria-focused genes, and 365 neuron-related genes [7, 8]
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