MicroRNAs as biomarkers of resilience or vulnerability to stress

Chen, R.J.; Kelly, Gregory M.; Sengupta, Abhishek; Heydendael, Willem; Nicholas, Ben; Beltrami, S.; Luz, Sandra; Peixoto, Lucı́a; Abel, Ted; Bhatnagar, Seema

doi:10.1016/j.neuroscience.2015.07.045

Cited by 89 publications

(72 citation statements)

References 40 publications

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“…In different individuals, or under different conditions, either active coping, characterized by the fight or flight response, or passive coping, characterized by immobility and withdrawal, can occur during exposure to stressors (Engel and Schmale, 1972;Koolhaas et al, 1999;Southwick et al, 2005;Wood and Bhatnagar, 2015). The present experiments used an animal model of repeated social defeat stress in which active and passive coping strategies dichotomize into either a resilient or vulnerable trait, respectively, as assessed post hoc by various neuroendocrine measures, behavioral tests (Wood et al, 2010;Chen et al, 2015;Wood and Bhatnagar, 2015;Finnell et al, 2017), and markers of inflammation (Pearson-Leary et al, 2017, 2019. Understanding whether such differences in coping strategy are associated with the subsequent development of sleep disturbances akin to those reported in PTSD may help to provide a basis for examining the mechanisms by which traumatic stress affects sleep in vulnerable individuals.…”

Section: Introductionmentioning

confidence: 99%

Passive Coping Strategies During Repeated Social Defeat Are Associated With Long-Lasting Changes in Sleep in Rats

Grafe

O’Mara

Branch

et al. 2020

Front. Syst. Neurosci.

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Exposure to severe stress has immediate and prolonged neuropsychiatric consequences and increases the risk of developing Posttraumatic Stress Disorder (PTSD). Importantly, PTSD develops in only a subset of individuals after exposure to a traumatic event, with the understanding of this selective vulnerability being very limited. Individuals who go on to develop PTSD after a traumatic experience typically demonstrate sleep disturbances including persistent insomnia and recurrent trauma-related nightmares. We previously established a repeated social defeat paradigm in which rats segregate into either passively or actively coping subpopulations, and we found that this distinction correlates with measures of vulnerability or resilience to stress. In this study, we examined differences between these two behavioral phenotypes in sleep changes resulting from repeated social defeat stress. Our data indicate that, compared to control and actively coping rats, passively coping rats have less slow-wave sleep (SWS) for at least 2 weeks after the end of a series of exposures to social defeat. Furthermore, resilient rats show less exaggerated motor activation at awakenings from rapid eye movement (REM) sleep and less fragmentation of REM sleep compared to control and passively coping rats. Together, these data associate a passive coping strategy in response to repeated social defeat stress with persisting sleep disturbances. Conversely, an active coping strategy may be associated with resilience to sleep disturbances. These findings may have both prognostic and therapeutic applications to stress-associated neuropsychiatric disorders, including PTSD.

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Section: Introductionmentioning

confidence: 99%

Passive Coping Strategies During Repeated Social Defeat Are Associated With Long-Lasting Changes in Sleep in Rats

Grafe

O’Mara

Branch

et al. 2020

Front. Syst. Neurosci.

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“…Clearly, further studies are needed to elucidate the mechanism by which miR-326 alters DRD2 after ELS. Nonetheless, resilience after adult social defeat stress in rats has been inversely correlated with miR-326 expression in the amygdala [60]. Bai et al [36] reported that the same 6 h maternal separation paradigm increased miR-16 expression in the hippocampus as compared with controls and animals who received chronic unpredictable stress.…”

Section: Preclinical Studiesmentioning

confidence: 99%

MicroRNA mediators of early life stress vulnerability to depression and suicidal behavior

2019

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Childhood environment can have a profound impact on brain structure and function. Epigenetic mechanisms have been shown to play a critical role in adaptive and maladaptive processes by regulating gene expression without changing the genome. Over the past few years, early life stress (ELS) has been established as a major risk factor for major depression and suicidal behavior along with other psychiatric illnesses in adulthood. In recent years, the emergence of small noncoding RNAs as a mega controller of gene expression has gained attention for their role in various disease processes. Among various noncoding RNAs, microRNAs (miRNAs) are the most studied and well characterized and have emerged as a major regulator of neural plasticity and higher brain functioning. More recently, although limited in number, studies are focusing on how miRNAs can play a role in the maladaptive processes associated with ELS both at adolescent and adult age and whether these processes are critical in developing depression and suicidal behavior. In this review, we critically evaluate how postnatal ELS relates to abnormalities in miRNA expression and functions from both animal and human literature and draw connections from these findings to depression and suicidal behavior later in life.

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“…Likewise, neural activity in the mPFC provides inhibitory control over conditioned fear (Do-Monte, Manzano-Nieves, Quinones-Laracuente, Ramos-Medina, & Quirk, 2015; Giustino & Maren, 2015), the neuroendocrine stress response (Radley, Gosselink, & Sawchenko, 2009), acquisition of anxiety and depression-like behavior (Vialou et al, 2014), and drug seeking behavior (Britt et al, 2012). Ventral portions of the mPFC (vmPFC) have also been implicated in behavioral and physiological responses to social defeat stress (Chen et al, 2015; Vialou, et al, 2014). In Syrian hamsters, acute social defeat stress leads to a dramatic shift from normal territorial aggression to submissive and defensive behavior during subsequent social interaction testing (Huhman et al, 2003).…”

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confidence: 99%

Social play in juvenile hamsters alters dendritic morphology in the medial prefrontal cortex and attenuates effects of social stress in adulthood.

Burleson¹,

Pedersen²,

Seddighi³

et al. 2016

Behavioral Neuroscience

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Social play is a fundamental aspect of behavioral development in many species. Social play deprivation in rats alters dendritic morphology in the ventromedial prefrontal cortex (vmPFC) and we have shown that this brain region regulates responses to social defeat stress in Syrian hamsters. In this study, we tested whether play deprivation during the juvenile period disrupts dendritic morphology in the prefrontal cortex and potentiates the effects of social defeat stress. At weaning, male hamsters were either group-housed with peers or pair-housed with their mother, with whom they do not play. In adulthood, animals received acute social defeat stress or no-defeat control treatment. The hamsters were then tested for a conditioned defeat response in a social interaction test with a novel intruder, and were also tested for social avoidance of a familiar opponent. Brains were collected for Golgi-Cox staining and analysis of dendritic morphology in the infralimbic (IL), prelimbic (PL), and orbitofrontal cortex (OFC). Play-deprived animals showed an increased conditioned defeat response and elevated avoidance of a familiar opponent compared to play-exposed animals. Also, play-deprived animals showed increased total length and branch points in apical dendrites of pyramidal neurons in the IL and PL cortices, but not in the OFC. These findings suggest that social play deprivation in juvenile hamsters disrupts neuronal development in the vmPFC and increases vulnerability to the effects of social stress in adulthood. Overall, these results suggest that social play is necessary for the natural dendritic pruning process during adolescence and promotes coping with stress in adulthood.

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MicroRNAs as biomarkers of resilience or vulnerability to stress

Cited by 89 publications

References 40 publications

Passive Coping Strategies During Repeated Social Defeat Are Associated With Long-Lasting Changes in Sleep in Rats

Passive Coping Strategies During Repeated Social Defeat Are Associated With Long-Lasting Changes in Sleep in Rats

MicroRNA mediators of early life stress vulnerability to depression and suicidal behavior

Social play in juvenile hamsters alters dendritic morphology in the medial prefrontal cortex and attenuates effects of social stress in adulthood.

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