Early life stress dampens stress responsiveness in adolescence: Evaluation of neuroendocrine reactivity and coping behavior

Hsiao, Young Ming; Tsai, Tsung-Chih; Lin, Yu Ting; Chen, Chien‐Chung; Huang, Chiung Chun; Hsu, Kuei Sen

doi:10.1016/j.psyneuen.2016.02.004

Cited by 40 publications

(37 citation statements)

References 58 publications

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“…In male mice, shifting the timing of ELS to P10-17 (or P10-20) also did not alter depression-like behaviors at baseline, but instead increased the risk that a second stress in adulthood would result in depression-like behaviors. These findings are in contrast to other rodent ELS paradigms that report baseline depression-like behaviors from early (<P14) postnatal stress in female mice 27 , and evidence that ELS prior to P9 may in fact blunt hippocampal plasticity and dampen responses to additional stress 28,29 . Studies of humans that experienced early life adversity have found earlier development of anxiety, depression, and other psychiatric illnesses, as well as latent vulnerability to these diseases [30][31][32] .…”

Section: Discussioncontrasting

confidence: 87%

Early life stress alters transcriptomic patterning across reward circuitry in male and female mice

Peña

Smith

Ramakrishnan

et al. 2019

Preprint

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Abuse, neglect, and other forms of early life stress (ELS) significantly increase risk for psychiatric disorders including depression. In this study, we show that ELS in a postnatal sensitive period increases sensitivity to adult stress in female mice, consistent with our earlier findings in male mice. We used RNA-sequencing in the ventral tegmental area, nucleus accumbens, and prefrontal cortex of male and female mice to show that adult stress is distinctly represented in the brain's transcriptome depending on ELS history. We identify: 1) biological pathways disrupted after ELS and associated with increased behavioral stress sensitivity, 2) putative transcriptional regulators of the effect of ELS on adult stress response, and 3) subsets of primed genes specifically associated with latent behavioral changes. We also provide transcriptomic evidence that ELS increases sensitivity to future stress through enhancement of known programs of cortical plasticity.

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Section: Discussioncontrasting

confidence: 87%

Early life stress alters transcriptomic patterning across reward circuitry in male and female mice

Peña

Smith

Ramakrishnan

et al. 2019

Preprint

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“…Several recent studies in mice reported impaired neurogenesis and cognition with early life stress [23], as well as altered CpG methylation in NR3C1 , the gene encoding the glucocorticoid receptor [24]. Similar adverse effects have been observed in humans with exposure to early life stress [25, 26]. This link was further bolstered by an overrepresentation analysis that showed an enrichment of AUC weekday cortisol-associated genes in GenRED Offspring blood and saliva with suicide-associated genes in prefrontal neurons as well as previously identified genes associated with cortisol stress reactivity in blood [20], indicating that there are consistent cross-tissue DNA methylation changes with cortisol dysregulation and a behavioral outcome such as suicide.…”

Section: Discussionmentioning

confidence: 83%

Discovery and replication of a peripheral tissue DNA methylation biosignature to augment a suicide prediction model

et al. 2016

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BackgroundSuicide is the second leading cause of death among adolescents in the USA, and rates are rising. Methods to identify individuals at risk are essential for implementing prevention strategies, and the development of a biomarker can potentially improve prediction of suicidal behaviors. Prediction of our previously reported SKA2 biomarker for suicide and PTSD is substantially improved by questionnaires assessing perceived stress or anxiety and is therefore reliant on psychological assessment. However, such stress-related states may also leave a biosignature that could equally improve suicide prediction. In genome-wide DNA methylation data, we observed significant overlap between waking cortisol-associated and suicide-associated DNA methylation in blood and the brain, respectively.ResultsUsing a custom bioinformatic brain to blood discovery algorithm, we derived a DNA methylation biosignature that interacts with SKA2 methylation to improve the prediction of suicidal ideation in our existing suicide prediction model across both blood and saliva data sets. This biosignature was independently validated in the Grady Trauma Project cohort and interacted with HPA axis metrics in the same cohort. The biosignature showed a relationship with immune status by its correlation with myeloid-derived cell proportions in all data sets and with IL-6 measures in a prospective postpartum depression cohort. Three probes showed significant correlations with the biosignature: cg08469255 (DDR1), cg22029879 (ARHGEF10), and cg24437859 (SHP1), of which SHP1 methylation correlated with immune measures.ConclusionsWe conclude that this biosignature interacts with SKA2 methylation to improve suicide prediction and may represent a biological state of immune and HPA axis modulation that mediates suicidal behavior.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0279-1) contains supplementary material, which is available to authorized users.

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“…Oxtr impairs long-term potentiation at EC¡CA2 synapses A recent study reported that long-term SRM in rats is mediated by OXT-dependent synaptic plasticity in the medial amygdala (MeA; Gur et al, 2014). In addition, we and others reported previously that OXT can enhance LTP at Schaffer collateral¡CA1 synapses and improve long-lasting spatial memory function during motherhood (Tomizawa et al, 2003;Lin et al, 2012).…”

Section: Conditional Deletion Of Ca2/ca3amentioning

confidence: 86%

“…Prominent glutamatergic inputs to CA2 pyramidal neurons come from the dentate gyrus, CA3 pyramidal neurons and the entorhinal cortex (EC;Kohara et al, 2014;Chevaleyre and Piskorowski, 2016). Furthermore, CA2 pyramidal neurons receive afferent inputs from the septum, medium raphe nucleus, basal nucleus of the amygdala, and hypothalamic paraventricular and supramammillary nuclei (Haglund et al, 1984;Pikkarainen et al, 1999;Cui et al, 2013;Zhang and Hernández, 2013;Chevaleyre and Piskorowski, 2016). Although little is known about its functional properties and physiological roles, growing evidence suggests that the CA2 is more than a passive transition region between the CA1 and CA3.…”

Section: Introductionmentioning

confidence: 99%

Conditional Deletion of Hippocampal CA2/CA3a Oxytocin Receptors Impairs the Persistence of Long-Term Social Recognition Memory in Mice

Lin¹,

Hsieh²,

et al. 2017

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Oxytocin (OXT) receptors (OXTRs) are prominently expressed in hippocampal CA2 and CA3 pyramidal neurons, but little is known about its physiological function. As the functional necessity of hippocampal CA2 for social memory processing, we tested whether CA2 OXTRs may contribute to long-term social recognition memory (SRM) formation. Here, we found that conditional deletion of from forebrain () or CA2/CA3a-restricted excitatory neurons in adult male mice impaired the persistence of long-term SRM but had no effect on sociability and preference for social novelty. Conditional deletion of CA2/CA3a showed no changes in anxiety-like behavior assessed using the open-field, elevated plus maze and novelty-suppressed feeding tests. Application of a highly selective OXTR agonist [Thr,Gly]-OXT to hippocampal slices resulted in an acute and lasting potentiation of excitatory synaptic responses in CA2 pyramidal neurons that relied on -methyl-d-aspartate receptor activation and calcium/calmodulin-dependent protein kinase II activity. In addition, mice displayed a defect in the induction of long-term potentiation, but not long-term depression, at the synapses between the entorhinal cortex and CA2 pyramidal neurons. Furthermore, deletion led to a reduced complexity of basal dendritic arbors of CA2 pyramidal neurons, but caused no alteration in the density of apical dendritic spines. Considering that the methodologies we have used to delete do not rule out targeting the neighboring CA3a region, these findings suggest that OXTR signaling in the CA2/CA3a is crucial for the persistence of long-term SRM. Oxytocin receptors (OXTRs) are abundantly expressed in hippocampal CA2 and CA3 regions, but there are little known about their physiological function. Taking advantage of the conditional knock-out mice, the present study highlights the importance of OXTR signaling in the induction of long-term potentiation at the synapses between the entorhinal cortex and CA2 pyramidal neurons and the persistence of long-term social recognition memory. Thus, OXTRs in the CA2/CA3a may provide a new target for therapeutic approaches to the treatment of social cognition deficits, which are often observed in patients with neuropsychiatric disorders.

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Early life stress dampens stress responsiveness in adolescence: Evaluation of neuroendocrine reactivity and coping behavior

Cited by 40 publications

References 58 publications

Early life stress alters transcriptomic patterning across reward circuitry in male and female mice

Early life stress alters transcriptomic patterning across reward circuitry in male and female mice

Discovery and replication of a peripheral tissue DNA methylation biosignature to augment a suicide prediction model

Conditional Deletion of Hippocampal CA2/CA3a Oxytocin Receptors Impairs the Persistence of Long-Term Social Recognition Memory in Mice

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