Role of MicroRNAs in the Synaptic Plasticity Dysfunction During Post-Traumatic Stress Disorder

PUBLIC ABSTRACT

At present, there is no definitive treatment and no cure for post-traumatic stress disorder (PTSD). Brain function of PTSD individuals is strongly impacted, especially with changes in brain plasticity. The goal of this proposal is to investigate micro-RNAs (mi-RNAs), novel non-coding transcripts of approximately 21 nucleotides, which can act as local synaptic modulators of the expression of coding messenger RNAs (mRNAs), to develop therapeutic applications for the reversal of brain malfunction caused by stress. This will allow for the alleviation of anxiety episodes in military and/or civilians associated with PTSD.

We hypothesize that mi-RNAs play a major role in the changes of synaptic plasticity after a stressful insult, by regulating local translation in the dendrites of limbic system neurons. Mi-RNAs in the central nervous system appear critical for controlling cell identity, and these play an important role in the development of brain function. In neurons, distances between nucleus and dendrite projections are long, making nuclear regulation of protein synthesis and structural change difficult. Mi-RNAs circumvent this difficulty by controlling translation not at the level of the nucleus, but on the machinery near the site of protein synthesis. Some of the end targets of mi-RNAs include signaling proteins that play important roles in plasticity and brain function. Any abnormality in the function of mi-RNAs will result in the disruption of the translation of mRNAs affecting proteins that mediate brain function, altering neural plasticity. Therefore, understanding the way the mi-RNA profile may change in PTSD will allow for therapeutic intervention.