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 85 publications

(67 citation statements)

References 40 publications

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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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Section: Preclinical Studiesmentioning

confidence: 99%

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

2019

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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).…”

mentioning

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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“…Notably, recent work studying biomarkers of resilience or vulnerability to stress in rats demonstrated that the expression of miR-708-5p along with miR-126a-3p was higher at the medial prefrontal cortex (mPFC) of vulnerable rats (Chen et al, 2015). The authors also demonstrated that resilient rats differed from vulnerable rats in the set of multiple blood-circulating miRNAs, namely, reduction in miR-139-5p, miR-28-3p, miR-326-3p, and miR-99b-5p in resilient animals and reduction in miR-24-2-5p, miR-27a-3p, miR-30e-5p, miR-3590-3p, miR-362-3p and miR-532-5p levels in vulnerable animals.…”

Section: Discussionmentioning

confidence: 99%

Evidence for Ancestral Programming of Resilience in a Two-Hit Stress Model

Faraji

Soltanpour

Ambeskovic

et al. 2017

Front. Behav. Neurosci.

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In a continuously stressful environment, the effects of recurrent prenatal stress (PS) may accumulate across generations and alter stress vulnerability and resilience. Here, we report in female rats that a family history of recurrent ancestral PS facilitates certain aspects of movement performance, and that these benefits are abolished by the experience of a second hit, induced by a silent ischemia during adulthood. Female F4-generation rats with and without a family history of cumulative multigenerational PS (MPS) were tested for skilled motor function before and after the induction of a minor ischemic insult by endothelin-1 infusion into the primary motor cortex. MPS resulted in improved skilled motor abilities and blunted hypothalamic-pituitary-adrenal (HPA) axis function compared to non-stressed rats. Deep sequencing revealed downregulation of miR-708 in MPS rats along with upregulation of its predicted target genes Mapk10 and Rasd2. Through miR-708 stress may regulate mitogen-activated protein kinase (MAPK) pathway activity. Hair trace elemental analysis revealed an increased Na/K ratio, which suggests a chronic shift in adrenal gland function. The ischemic lesion activated the HPA axis in MPS rats only; the lesion, however, abolished the advantage of MPS in skilled reaching. The findings indicate that MPS generates adaptive flexibility in movement, which is challenged by a second stressor, such as a neuropathological condition. Thus, a second “hit” by a stressor may limit behavioral flexibility and neural plasticity associated with ancestral stress.

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MicroRNAs as biomarkers of resilience or vulnerability to stress

Cited by 85 publications

References 40 publications

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

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.

Evidence for Ancestral Programming of Resilience in a Two-Hit Stress Model

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