WFS1 gene as a putative biomarker for development of post-traumatic syndrome in an animal model

Abstract

Post-traumatic stress disorder (PTSD) is an anxiety disorder that may develop after the experiencing or witnessing of a life-threatening event. PTSD is defined by the coexistence of three clusters of symptoms: re-experiencing, avoidance and hyperarousal, which persist for at least 1 month in survivors of the event (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). Using an established model of PTSD, we addressed the well-accepted clinical finding that only a minority (about 20%) of the individuals exposed to a traumatic event develop PTSD. Moreover, we followed individual rat behavior for up to a month, and then treated the PTSD-like animals with citalopram. Our data demonstrate high face (20% of rats exposed to a reminder of the stressor develop symptoms characteristic of PTSD) and predictive (response to citalopram) validities. Based on these validities we identified alterations in the Wolframin gene in the CA1 and amygdala regions, specifically in exposed PTSD-like rats, which were normalized after treatment with citalopram. We suggest the Wolframin gene as a putative biomarker for PTSD. Since Wolframin gene undergoes alternative splicing and has polymorphism in the population, it may serve a future marker for identification of the vulnerable population exposed to a traumatic event.

Biological studies of post-traumatic stress disorder

“…206 Changes in hippocampal serotonin levels have been implicated in SPS/stress–restress models, 207 and a serotonin reuptake inhibitor reversed behavioral changes in a PredEx model. 208 Increases in 5-HT1A receptor levels in the dorsal raphe nucleus 209 and hippocampus 210 have been reported in SPS and time-dependent sensitization models, respectively, and 5-HT1A receptor antagonist (WAY-100635) inhibited SPS-induced increases in GR and CRF expression in hippocampus and hypothalamus. 211 In an SPS model, amygdala 5HT2c receptor gene expression was increased, and administration of a 5HT2c receptor antagonist decreased SPS-induced contextual fear-related freezing.…”

Association of aggression with a novel microRNA binding site polymorphism in the wolframin gene

“…WFS1 deficient mice had a dramatic decrease in the mass of the pancreatic islets and a serious impairment of glucose homeostasis [Ishihara et al, 2004]. Results from behavioral studies of the WFS1 knockout mouse suggested that it could be used as an animal model of mood disorder [Kato et al, 2008], impaired behavioral stress adaptation [Luuk et al, 2009] and post-traumatic stress disorder [Kesner et al, 2009].…”

The relevance of epigenetics to PTSD: Implications for the DSM‐V

“…The preeminent animal models of PTSD (e.g., Cohen, Matar, Richter-Levin, & Zohar, 2006; Kesner et al, 2009; Siegmund & Wotjak, 2006; Zoladz, Conrad, Fleschner, & Diamond, 2008) have relied on stress theory, stress sensitization, and fear conditioning to explain biological mechanisms relevant to PTSD. Epigenetic models complement these approaches by addressing the persistence of the response to a stressor, which is not well explained by classic models of stress and fear or the neural architecture of fear.…”