A new study has identified a link between fear memory and TIA1, a prion-related RNA-binding protein whose capacity to form various types of intracellular aggregates has been implicated in neurodegenerative disease.1,2 Going forward, the finding could usher in fresh therapeutic targets in conditions such as post-traumatic stress disorder (PTSD) and anxiety.
Prions are misfolded proteins that have long been linked to several serious neurological diseases including mad cow disease and its human counterpart Creutzfeldt–Jakob disease (CJD). More recently, however, esteemed Nobel-Prize winner Eric R. Kandel and colleagues at Columbia University, USA, have uncovered several beneficial and functional prions, for example CPEB3, which assist in the maintenance of long-term memories.
In their most recent work, published March 12 in Cell Reports, the authors present research exploring the role of TIA1 in fear memory.1 Using mice models of either deletion or overexpression of TIA1, the researchers investigated how both scenarios would affect conditioned odour response. Here, repeated electrical foot shocks were administered when mice came in contact with the odour. After this conditioning, mice exhibited stress and avoidance behaviour whenever they detected the smell.
In testing, deletion of TIA1 in the mice led to significantly heightened avoidance behaviour in female mice only, with no apparent effect on males. Interestingly, this indicates a physiological and partly sex-specific function of TIA1.
Conversely, when TIA1 was overexpressed in the ventral hippocampus, the researchers observed inhibition of fear memory and odour avoidance in both female and male mice. “We propose that TIA1 is a genetic modifier of conditioned odour avoidance behaviour in mice, and our findings support the idea that TIA1 is a candidate susceptibility locus in stress-linked psychopathology,” the authors write.1
While open questions remain as to the molecular and cellular basis for how TIA1 overexpression influences both synaptic plasticity and behaviour change, TIA1 may have great value as a therapeutic target in the future.
- Rayman JB, Hijazi J, Xiang Li, et al. Genetic Perturbation of TIA1 Reveals a Physiological Role in Fear Memory. Cell Reports. 2019;28;2970–83.
- Scientists identify gene that keeps PTSD-like behavior at bay in female mice. Neuroscience News, March 12, 2019.