Stress-induced changes in the molecular processes underlying fear memories: implications for PTSD and relevant animal models

Molecular Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Most of the fear literature on humans and animals tests healthy individuals. However, memories can differ between individuals those previously exposed to traumatic stress, such as a car accident, sexual abuse, military combat personal assault. Traumatic stress lead post-traumatic disorder (PTSD) which presents alterations in memories, an impairment extinction recall. PTSD-like animal models are single highly stressful experience laboratory, immobilization or single-prolonged stress. Some days later, model be tested procedures that help uncover molecular mechanisms memories. In this review, there discussed stress-induced patients with PTSD models. The focus is effects estradiol cortisol/corticosterone hormones different genes, FKBP prolyl isomerase 5 gene (FKBP5) - FK506 binding protein 51 (FKBP51), pituitary adenylate cyclase-activating peptide (PACAP) polypeptide type I receptor (PAC1R), endocannabinoid (eCB) system tropomyosin kinase B (TrkB) brain-derived neurotrophic factor (BDNF). conclusion greater emphasis should placed investigating PTSD, through direct testing use relevant

Язык: Английский

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AI as an accelerator for defining new problems that transcends boundaries

BioData Mining, Год журнала: 2025, Номер 18(1)

Опубликована: Фев. 18, 2025

Interdisciplinary, transdisciplinary, convergence, and No-Boundary Thinking (NBT) research are methodology technology-agnostic approaches to problem solving. The focus is on defining problems informed by access multiple knowledge sources expert perspectives across different domains, with the goal of accessing all available perspectives. While could be seen as a difficult attain objective, recent rise AI we might closer approaching this goal. We review several examples methodologies technologies that have been used put these strategies into action, but primary paper how advances in now enable quantum leap forward new problems. By leveraging capacity synthesize from tools can propose candidate definitions. uniquely able draw upon many more than any individual-or even very large team-could. Coupled human intelligence, better defined address complex scholarly or societal challenges.

Язык: Английский

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An Update on the Psychiatric Genomics of Posttraumatic Stress Disorder (PTSD)

Psychiatric Clinics of North America, Год журнала: 2025, Номер 48(2), С. 403 - 415

Опубликована: Март 4, 2025

Язык: Английский

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The evolving neurobiology of early-life stress

Neuron, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Corticosteroid‐regulated gene transcription in SH‐SY5Y‐derived neurons: Insights into the mineralocorticoid and glucocorticoid receptor‐mediated response

Journal of Neuroendocrinology, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

Abstract Post‐traumatic stress disorder (PTSD) and major depressive (MDD) are debilitating stress‐related psychiatric disorders that can develop following exposure to traumatic events or chronic in some individuals. The neurobiological processes leading disease remain largely unknown. Among others, these characterized by a dysregulated hypothalamic–pituitary–adrenal axis, which is regulated the glucocorticoid receptor (GR) mineralocorticoid (MR). This leads altered downstream corticosteroid‐induced gene expression. In vitro models promising tools investigate specific underpinnings of response brain. Here, we investigated suitability SH‐SY5Y‐derived neurons as cost‐efficient system study role GR MR neuronal response. were characterized, exposed corticosteroids, analyzed on transcriptomic proteomic levels. We show (i) express sufficient seemingly functional allow transcription, (ii) three corticosteroids cortisol, dexamethasone, aldosterone, induced similar effects, (iii) antagonist spironolactone mildly attenuated effects dexamethasone FKBP5 , DUSP1 SUPV3L1 . Mifepristone did not significantly alter effect aldosterone. (iv) Integrating alterations corticosteroid‐exposed with those iPSC‐derived showed concordant two systems. To determine translational validity, compared expression transcriptome postmortem brain samples from individuals PTSD MDD, yielding stronger negative correlations corticosteroid signatures than MDD signatures. Upon further refinement validation, may serve simplistic tool implicated molecular networks around MR. Strengthening our insight into receptors' functions improves understanding commonly such MDD.

Язык: Английский

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A multi-omic approach implicates novel protein dysregulation in post-traumatic stress disorder

Genome Medicine, Год журнала: 2025, Номер 17(1)

Опубликована: Апрель 29, 2025

Abstract Background Post-traumatic stress disorder (PTSD) is a common and disabling psychiatric disorder. PTSD involves multiple brain regions often comorbid with other disorders, such as major depressive (MDD). Recent genome-wide association studies (GWASs) have identified many risk loci transcriptomics of postmortem found differentially expressed genes associated cases. In this study, we integrated measures across modalities to identify convergent molecular effects in the brain. Methods We performed tandem mass spectrometry (MS/MS) on large cohort donors ( N = 66) two prefrontal cortical areas, dorsolateral cortex (DLPFC), subgenual (sgPFC). also coupled proteomics data microRNA (miRNA) profiling from RNA-seq small-RNA sequencing, respectively for same cohort. Additionally, utilized published GWAS results disorders integrative analysis. Results proteins co-expression protein modules disrupted by PTSD. Integrative analysis miRNA pointed hsa-mir-589 regulatory responsible dysregulation neuronal networks PTSD, including gamma-aminobutyric acid (GABA) vesicular transporter, SLC32A1. addition, significant enrichment autism spectrum (ASD) (MDD) within modules, suggesting shared pathology. Conclusions mRNA expression MDD, control (CON) brains divergent processes genomic modalities. substantially expand number downregulation GABAergic proteome. This provides novel framework future integrating proteomic non-coding RNAs human studies.

Язык: Английский

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Systematic review and mega-analysis of the peripheral blood transcriptome in depression implicates dysregulation of lymphoid cells and histones

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 5, 2025

Depression has been associated with transcriptomic changes in peripheral blood. However, the contribution of specific immune cell subsets or pathways remains unclear, and findings have variable across previous studies, which not tended to account for sample cellular composition. We performed a systematic review blood transcriptome studies depression. For five datasets meeting criteria (total N=6,011), we harmonized reprocessing cell-composition-adjusted differential gene transcript analyses, followed by bias- inflation-adjusted weighted Z-score mega-analysis. investigated biological implicated results. also sex-stratified network mega-analysis using consensus co-expression analysis (WGCNA). Few genes showed robust expression (DGE) was reproducibly decreases replication-dependent histones, decrease oxidative phosphorylation females only. Cell source analyses lymphoid cells (T NK cells) as likely contributors depression signature. WGCNA revealed multiple modules depression, PUF60 -related module upregulated both female male analyses. Two predicted be causally relevant transcriptome-wide association ( GPX4 GYPE ) significant DGE. These results are convergent immunogenetic evidence implicating dysregulation while highlighting histone alterations key molecular signature They indicate importance large-scale biomarker discovery context heterogeneous disorders like

Язык: Английский

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Advancing an Inflammatory Subtype of Major Depression

American Journal of Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Май 7, 2025

Chronic inflammation plays a prominent role in multiple medical disorders, including psychiatric diseases such as major depression. Exposure to inflammatory stimuli leads changes neurotransmitter systems and neurocircuits the brain that are associated with depressive symptoms. Blockade of cytokines can reduce symptoms medically ill healthy individuals Increased levels biomarkers an overrepresentation neurovegetative symptoms, anhedonia, fatigue, psychomotor slowing, predict response antidepressant treatments. Importantly, however, increased occur only subgroup Thus, there appears be subset patients depression unique symptom presentation treatment whose disease is primarily driven by inflammation. Further identifying characterizing this subtype foster development treatments targeting immune system its effects on brain. Moreover, using mechanism-based approach parsing heterogeneity depression, we refine our diagnostic nosology model strategy for precision medicine targeted therapeutics psychiatry.

Язык: Английский

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Canonical and non-canonical roles of oligodendrocyte precursor cells in mental disorders

npj Mental Health Research, Год журнала: 2025, Номер 4(1)

Опубликована: Май 15, 2025

Abstract Psychiatric research has shifted from a neuroncentric view to understanding mental disorders as disturbances of heterogeneous brain networks. Oligodendrocyte precursor cells (OPCs)— actively involved in the modulation neuronal functions – are altered psychiatric patients, but extent and related consequences unclear. This review explores canonical non-canonical OPC-related pathways schizophrenia, bipolar disorder, post-traumatic stress depression humans, highlighting potential mechanisms shared across diagnostic entities.

Язык: Английский

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Idebenone Mitigates Traumatic-Brain-Injury-Triggered Gene Expression Changes to Ephrin-A and Dopamine Signaling Pathways While Increasing Microglial Genes

Cells, Год журнала: 2025, Номер 14(11), С. 824 - 824

Опубликована: Июнь 1, 2025

Traumatic brain injury (TBI) leads to persistent pro-inflammatory microglial activation implicated in neurodegeneration. Idebenone, a coenzyme Q10 analogue that interacts with both mitochondria and the tyrosine kinase adaptor SHC1, inhibits aspects of vitro. We used NanoString neuropathology Panel test hypothesis idebenone post-treatment mitigates TBI-pathology-associated acute gene expression changes by moderating response injury. Controlled cortical impact adult male mice increased signature peri-lesional cortex at 24 h post-TBI. Unexpectedly, several genes upregulated TBI were further post-injury administration. However, significantly attenuated TBI-mediated perturbations associated behavior, particularly ontology–biological process (GO:BP) pathways “ephrin receptor signaling” “dopamine metabolic process”. Gene co-expression analysis correlated levels complement component 1q (C1q) neurotrophin Ntrk1 large (>3-fold) TBI-induced decreases dopamine Drd1 Drd2 mitigated treatment. Bioinformatics identified SUZ12 as candidate transcriptional regulator idebenone-modified changes. Overall, results suggest may enhance number within first identify ephrin-A signaling novel targets.

Язык: Английский

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