Mitochondrial Gene Expression Profiles and Metabolic Pathways in the Amygdala Associated with Exaggerated Fear in an Animal Model of PTSD

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.

The inulin-type oligosaccharides extract from morinda officinalis, a traditional Chinese herb, ameliorated behavioral deficits in an animal model of post-traumatic stress disorder

“…Also, the decreased open arm exploration in the EPM test following exposure to SPS was consistent with the previous reports (Zhang et al 2012). One possible explanation for the behavioral deficits was that SPS elicited an acquisition of conditioned fear, such as exaggerated fear (Li et al 2014). The dampened allopregnanolone in the central nervous system (CNS) was associated with PTSD-like behavioral deficits (Agís-Balboa et al 2007).…”

The prevalence and risk of metabolic syndrome and its components among people with posttraumatic stress disorder: a systematic review and meta-analysis

“…Emerging evidence suggests that both share pathophysiological features, including hypothalamic-pituitary-adrenal (HPA) and sympathoadrenomedullary dysfunction [46,47], inflammation [48], common genetic links and epigenetic interactions [49,50]. Third the extent to which traumatic experiences associated with physical injury may moderate associations between PTSD and MetS need to be examined, particularly in relation to compromised function of the endocrine organs.…”

Global arginine bioavailability, a marker of nitric oxide synthetic capacity, is decreased in PTSD and correlated with symptom severity and markers of inflammation

“…Recent evidence suggests that the psychiatric, physical and biological aspects of PTSD and related stress disorders may be associated with significant dysfunctions in several cellular processes including alterations in inflammation (Lindqvist et al 2014, Wilson et al 2013, oxidative stress (Ceprnja et al 2011, Wilson et al 2013, telomere homeostasis (Jergovic et al 2014, O'Donovan et al 2011), neuroendocrine regulation (Rasmusson et al 2010, Yehuda 2001, mitochondrial activity (Li et al 2014, Mellon et al 2015, Su et al 2008) and nitric oxide (NO) production (Bugajski 1999, Harris et al 2000, Lopez-Figueroa et al 1998, Persoons et al 1995, Yeh et al 2002.…”