MicroRNA regulation of persistent stress-enhanced memory

Sillivan, Stephanie E.; Jamieson, Sarah E.; Nijs, Laurence de; Jones, Meghan E.; Snijders, Clara; Klengel, Torsten; Joseph, Naima T.; Krauskopf, Julian; Kleinjans, Jos; Vinkers, Christiaan H.; Boks, Marco P.; Geuze, Elbert; Vermetten, Eric; Berretta, Sabina; Ressler, Kerry J.; Rutten, Bart P. F.; Rumbaugh, Gavin; Miller, Courtney A.

doi:10.1038/s41380-019-0432-2

Cited by 33 publications

(26 citation statements)

References 43 publications

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“…Consistent with this hypothesis, we recently demonstrated that exposure to a single acute stressor (120 min of restraint stress) induces a change in the molecular profile of the BLA, including differential expression of miRNAs an entire month after stress (Sillivan et al 2019b). Differential miRNA expression has also been reported in the serum of patients with PTSD (Zhou et al 2014;Martin et al 2017;Sillivan et al 2019a) and between rats selectively bred for high or low stress reactivity (Cohen et al 2017). The behavioral consequences of stress exposure have also been linked to miRNA function in the amygdala in several reports.…”

supporting

confidence: 53%

“…miRNAs are small, approximately 22-24 nt long, noncoding RNAs that repress translation of target mRNAs (Filipowicz et al 2008;Gebert and MacRae 2019). miRNAs interact with multiple functional targets directly at the 3 ′ untranslated region of the target mRNA based on complimentary sequences and, therefore, have been hypothesized to support the complex patterns of gene regulation required to support not only the initial formation of longterm memory, but also the persistence of remote memory (Sillivan et al 2019a). In an early example linking miRNAs to learning and memory, knockdown of Dicer1, an enzyme required for mature miRNA processing, enhanced memory performance in the Morris Water Maze, trace FC, and contextual FC (Konopka et al 2010), confirming that miRNA function influences recent memory performance in several different types of tasks.…”

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confidence: 99%

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microRNA mir-598-3p mediates susceptibility to stress enhancement of remote fear memory

et al. 2019

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microRNAs (miRNAs) have emerged as potent regulators of learning, recent memory, and extinction. However, our understanding of miRNAs directly involved in regulating complex psychiatric conditions perpetuated by aberrant memory, such as in posttraumatic stress disorder (PTSD), remains limited. To begin to address the role of miRNAs in persistent memories, we performed small-RNA sequencing on basolateral amygdala (BLA) tissue and identified miRNAs altered by auditory fear conditioning (FC) one month after training. mir-598-3p, a highly conserved miRNA previously unstudied in the brain, was down-regulated in the BLA. Further decreasing BLA mir-598-3p levels did not increase strength of the remote fear memory. Given that stress is a critical component in PTSD, we next assessed the impact of stress and stress-enhanced fear learning (SEFL) on mir-598-3p levels, finding the miRNA is elevated in the BLA of male, but not female, mice susceptible to the effects of stress in SEFL. Accordingly, intra-BLA inhibition of mir-598-3p interfered with expression and extinction of the remote fear memory in male, but not female, mice. This effect could not be attributed to an anxiolytic effect of miRNA inhibition. Finally, bioinformatic analysis following quantitative proteomics on BLA tissue collected 30 d post-SEFL training identified putative mir-598-3p targets and related pathways mediating the differential susceptibility, with evidence for regulation of the actin cytoskeleton, the core mediator of structural plasticity. Taken together, the results suggest BLA mir-598-3p may be recruited by stress to mediate a critical switch from a salient remote fear memory to one that is enhanced and extinction-resistant.

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confidence: 53%

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confidence: 99%

microRNA mir-598-3p mediates susceptibility to stress enhancement of remote fear memory

et al. 2019

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“…miRNAs are single-stranded RNA molecules 18-25 nucleotides in length that regulate gene expression in many cellular processes (2,27). Although the protective role of miR-135b was previously reported in neurons (16,17), the expression pattern and specific role of miR-135b in AIS remain poorly understood. The present study demonstrated that miR-135b expression in the peripheral blood samples obtained from the IS group was higher compared with the healthy control group.…”

Section: Discussionmentioning

confidence: 98%

“…The neuroprotective role of miR-135b in SH-SY5Y cells and stress-enhanced memory has been previously demonstrated (16,17). In Parkinson's disease (PD), the protective role of miR-135b is achieved by targeting GSK-3β in SH-SY5Y cells intoxicated with 1-methyl-4-phenyl-pyridinium (16).…”

Section: Introductionmentioning

confidence: 97%

“…In Parkinson's disease (PD), the protective role of miR-135b is achieved by targeting GSK-3β in SH-SY5Y cells intoxicated with 1-methyl-4-phenyl-pyridinium (16). Additionally, overexpression of miR-135b-5p in the basolateral amygdala complex of stress-resilient animals increased remote fear memory expression and contributed to spontaneous renewal 14 days after death (17). These observations suggested the potentially important role of miR-135b in cerebral neurons.…”

Section: Introductionmentioning

confidence: 99%

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miR-135b levels in the peripheral blood serve as a marker associated with acute ischemic stroke

Yang

Wang³

et al. 2020

Exp Ther Med

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The protective role of microRNA (miR)-135b in cerebral neurons has been previously identified. However, to the best of our knowledge, the involvement of miR-135b in acute ischemic stroke has yet to be elucidated. The present study aimed to investigate the expression profile of miR-135b in peripheral blood obtained from patients with acute ischemic stroke. A total of 76 patients with acute ischemic stroke were selected as the case group, which included 33 cases of aorta atheromatous plague, 19 cases of cardioembolism, 16 cases of small arterial occlusion and 8 cases with unknown causes. In addition, 60 healthy subjects were selected as the control group. Reverse transcription-quantitative PCR was used to measure the expression of miR-135b in the peripheral blood of the patients. The National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate the severity of acute ischemic stroke. The relationship between miR-135b levels and acute stroke was subsequently analyzed. The expression of miR-135b in the peripheral blood of the case group was found to be significantly higher compared with that in the control group. By contrast, the expression levels of miR-135b in the case group did not differ significantly between the different etiology types of acute ischemic stroke. In addition, a significant positive correlation was observed between levels of miR-135b expression and NIHSS scores. Further analysis demonstrated that hypertension, hyperglycemia, platelet count, international normalized ratio and miR-135b were risk factors for acute ischemic stroke. Based on bioinformatics analysis, a conserved binding site for miR-135b was identified in the 3'-untranslated region of the transient receptor potential cation channel subfamily C member 6 (TRPC6). Dual luciferase reporter and western blot analysis showed that TRPC6 was a target gene of miR-135b. In conclusion, data from the present study suggest that elevated expression of miR-135b in the peripheral blood of patients with acute ischemic stroke is closely associated with disease severity.

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Sex differences in acute early life stress‐enhanced fear learning in adult rats

Minshall,

Skipper,

Riddle

et al. 2024

Developmental Psychobiology

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Patients diagnosed with posttraumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms resulting from exposure to trauma. Women are twice as likely to be diagnosed with anxiety and PTSD compared to men; however, the reason for this vulnerability remains unknown. We conducted four experiments where we first demonstrated a female vulnerability to stress‐enhanced fear learning (SEFL) with a moderate, acute early life stress (aELS) exposure (4 footshocks in a single session), compared to a more intense aELS exposure (15 footshocks in a single session) where males and females demonstrated comparable SEFL. Next, we demonstrated that this female vulnerability does not result from differences in footshock reactivity or contextual fear conditioning during the aELS exposure. Finally, using gonadectomy or sham surgeries in adult male and female rats, we showed that circulating levels of gonadal steroid hormones at the time of adult fear conditioning do not explain the female vulnerability to SEFL. Additional research is needed to determine whether this vulnerability can be explained by organizational effects of gonadal steroid hormones or differences in sex chromosome gene expression. Doing so is critical for a better understanding of increased female vulnerability to certain psychiatric diseases.

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MicroRNA regulation of persistent stress-enhanced memory

Cited by 33 publications

References 43 publications

microRNA mir-598-3p mediates susceptibility to stress enhancement of remote fear memory

microRNA mir-598-3p mediates susceptibility to stress enhancement of remote fear memory

miR-135b levels in the peripheral blood serve as a marker associated with acute ischemic stroke

Sex differences in acute early life stress‐enhanced fear learning in adult rats

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