Summary: The NTRK2 gene has been implicated in resilience to developing PTSD following psychologically traumatic events. Previous studies outlined the role NTRK2 plays in memory formation. Those with increased regulation of the gene developed fewer traumatic memories following traumatic experiences.
Source: University of Basel
The endogenous regulation of a specific gene is associated with a reduced risk of developing post-traumatic stress disorder following a terrifying experience. In particular, traumatic memories of the experience are less severe. Researchers from the University of Basel have reported these findings in the scientific journal PNAS.
Traumatic experiences, such as an accident, rape or torture, can become deeply entrenched in a person’s memory and cause symptoms of post-traumatic stress disorder (PTSD) even years later. The stress hormone cortisol plays a vital role in the regulation of these memory processes, as demonstrated by a number of studies, including those from the research team led by Professor Dominique de Quervain at the University of Basel.
In their current project, de Quervain’s team took a closer look at the genes involved in cortisol signaling. Specifically, they determined the extent to which these genes are subject to chemical regulation by methyl groups on the DNA molecule. Vanja Vukojevic, one of the lead authors of the study, analyzed DNA methylation in two groups of people affected by trauma, namely 463 survivors of the Ugandan civil war and 350 survivors of the genocide in Rwanda.
In both groups, those who showed stronger regulation of the gene NTRK2 were at less risk of developing PTSD. The researchers were also able to rule out with a high degree of certainty that the trauma itself leads to an altered regulation of this gene. They found no link between the severity of the trauma and the extent of DNA methylation, which suggests that the latter existed before the traumatic experience.
Several basic studies have already shown that the gene NTRK2 plays a key role in memory formation. Indeed, in the current study, individuals with stronger regulation of this gene had fewer traumatic memories. The researchers also found that the regulatory mechanism – DNA methylation on the gene NTRK2 – was also linked to memory in 568 non-traumatized individuals. Those with stronger methylation of the gene performed worse when it came to remembering images they had seen previously. They also showed altered brain activity in regions important for memory during the tests.
These results suggest that increased regulation of the NTRK2 gene reduces memory formation. As a result, traumatic experiences do not become as entrenched in the memory, reducing the risk of developing PTSD. The researchers hope that this mechanism will contribute to the development of new therapies, which may also help in cases of existing PTSD by preventing recurrent unpleasant recollections from further cementing the traumatic memory.
The current study is part of the Basel Genetics Memory Project of the Transfaculty Research Platform Molecular and Cognitive Neurosciences, led by Professor Andreas Papassotiropoulos and Professor Dominique de Quervain. The aim is for the findings to be transferred from basic research into clinical projects as quickly as possible.
About this trauma and genetics research article
Source: University of Basel Contacts: Dominique de Quervain – University of Basel Image Source: The image is credited to University of Basel.
Noradrenergic activation of the basolateral amygdala maintains hippocampus-dependent accuracy of remote memory
Emotional enhancement of memory by noradrenergic mechanisms is well-described, but the long-term consequences of such enhancement are poorly understood. Over time, memory traces are thought to undergo a neural reorganization, that is, a systems consolidation, during which they are, at least partly, transferred from the hippocampus to neocortical networks. This transfer is accompanied by a decrease in episodic detailedness. Here we investigated whether norepinephrine (NE) administration into the basolateral amygdala after training on an inhibitory avoidance discrimination task, comprising two distinct training contexts, alters systems consolidation dynamics to maintain episodic-like accuracy and hippocampus dependency of remote memory. At a 2-d retention test, both saline- and NE-treated rats accurately discriminated the training context in which they had received footshock. Hippocampal inactivation with muscimol before retention testing disrupted discrimination of the shock context in both treatment groups. At 28 d, saline-treated rats showed hippocampus-independent retrieval and lack of discrimination. In contrast, NE-treated rats continued to display accurate memory of the shock–context association. Hippocampal inactivation at this remote retention test blocked episodic-like accuracy and induced a general memory impairment. These findings suggest that the NE treatment altered systems consolidation dynamics by maintaining hippocampal involvement in the memory. This shift in systems consolidation was paralleled by time-regulated DNA methylation and transcriptional changes of memory-related genes, namely Reln and Pkmζ, in the hippocampus and neocortex. The findings provide evidence suggesting that consolidation of emotional memories by noradrenergic mechanisms alters systems consolidation dynamics and, as a consequence, influences the maintenance of long-term episodic-like accuracy of memory.