microRNA regulation of persistent stress-enhanced memory

Sillivan, S. E.; Jamieson, S.; de Nijs, L.; Jones, M.; Snijders, C.; Klengel, T.; Joseph, N. F.; Krauskopf, J.; Kleinjans, J.; Vinkers, C. H.; Boks, M. P.; Geuze, E.; Vermetten, E.; Ressler, K. J.; Rutten, B. P.; Rumbaugh, G.; Miller, C.

doi:10.1101/379594

bioRxiv · 10.1101/379594

microRNA regulation of persistent stress-enhanced memory

Sillivan, S. E.·Jamieson, S.·de Nijs, L.·Jones, M.·Snijders, C.·Klengel, T.·Joseph, N. F.·Krauskopf, J.·Kleinjans, J.·Vinkers, C. H.·Boks, M. P.·Geuze, E.·Vermetten, E.·Ressler, K. J.·Rutten, B. P.·Rumbaugh, G.·Miller, C.

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Abstract

Disruption 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.\n\nOne Sentence Summarymir-135 can be manipulated to weaken persistent, stress-associated memory and serve as a biomarker of PTSD.

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Sillivan, S. E., Jamieson, S., de Nijs, L., Jones, M., Snijders, C., Klengel, T., Joseph, N. F., Krauskopf, J., Kleinjans, J., Vinkers, C. H., Boks, M. P., Geuze, E., Vermetten, E., Ressler, K. J., Rutten, B. P., Rumbaugh, G., Miller, C.. 2018-07-28. microRNA regulation of persistent stress-enhanced memory. https://doi.org/10.1101/379594

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