MicroRNA regulation of persistent stress-enhanced memory

• DOI: 10.1038/s41380-019-0432-2
• Publication Date: 2019-05-29T14:03:53Z
• Authors: Stephanie E. Daws; Sarah Jamieson; Laurence de Nijs; Meghan Jones; Clara Snijders; Torsten Klengel; Nadine F. Joseph; Julian Krauskopf; Jos Kleinjans; Christiaan H. Vin...; Marco P. M. Boks; Elbert Geuze; Eric Vermetten; Sabina Berretta; Kerry J. Ressler; Bart P. F. Rutten; Gavin Rumbaugh; Courtney A. Miller
• Keywords: Basolateral amygdala; Impaired memory; Extinction (optical mineralogy)

AbstractDisruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. Using a stress-enhanced fear learning protocol that results in differential susceptibility in inbred mice, we integrated small-RNA sequencing with quantitative proteomics on basolateral amygdala tissue collected one month after training. We identified persistently changed microRNAs, including mir-135b-5p, and predicted target proteins associated with PTSD-like heightened fear expression. Functional manipulations of mir-135b-5p bidirectionally modulated stress-associated memory. mir-135b-5p is expressed in human amygdala and its passenger strand was elevated in serum from a well-characterized military PTSD cohort. miR-135b-5p is a therapeutic target for dampening persistent, stress-enhanced memory and its passenger strand a potential biomarker for responsivity to a mir-135-based therapeutic.One Sentence Summarymir-135 can be manipulated to weaken persistent, stress-associated memory and serve as a biomarker of PTSD.