Recent Genetics and Epigenetics Approaches to PTSD

Current Psychiatry Reports, Journal Year: 2018, Volume and Issue: 20(5)

Published: April 5, 2018

Language: Английский

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Physical Exercise and Epigenetic Modifications in Skeletal Muscle

Sports Medicine, Journal Year: 2019, Volume and Issue: 49(4), P. 509 - 523

Published: Feb. 18, 2019

Language: Английский

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Long noncoding RNAs: a missing link in osteoporosis

Bone Research, Journal Year: 2019, Volume and Issue: 7(1)

Published: March 27, 2019

Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk, particularly the vertebrae hip. This condition associated morbidity mortality increase with population ageing. Long noncoding (lnc) RNAs are transcripts longer than 200 nucleotides not translated into proteins, but play important regulatory roles transcriptional post-transcriptional regulation. Their contribution to onset development increasingly recognized. Herein, we present an integrative revision on studies implicate lncRNAs osteoporosis support their potential use as therapeutic tools. Firstly, current evidence involvement cellular molecular mechanisms linked its major complication, fragility fractures, reviewed. We analyze osteogenesis, osteoclastogenesis, healing events from human animal model studies. Secondly, alterations at genetic transcriptomic level discussed risk factors new circulating biomarkers for diagnosis. Finally, conclude debating possibilities, persisting difficulties, future prospects using treatment osteoporosis.

Language: Английский

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Cell-type-specific epigenetic effects of early life stress on the brain

Translational Psychiatry, Journal Year: 2022, Volume and Issue: 12(1)

Published: Aug. 10, 2022

Early life stress (ELS) induces long-term phenotypic adaptations that contribute to increased vulnerability a host of neuropsychiatric disorders. Epigenetic mechanisms, including DNA methylation, histone modifications and non-coding RNA, are proposed link between environmental stressors, alterations in gene expression, phenotypes. play primary role shaping functional differences cell types can be modified by perturbations, especially early development. Together with contributions from genetic variation, epigenetic mechanisms orchestrate patterns expression within specific variation individuals. To date, many studies have provided insights into changes resulting ELS. However, most these examined heterogenous brain tissue, despite evidence cell-type-specific phenotypes associated In this review, we focus on rodent human induced ELS select isolated the or genes cell-type-restricted neurons, microglia, astrocytes, oligodendrocytes. Although significant challenges remain, future using approaches enable important mechanistic insight effects function.

Language: Английский

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Single-Nucleus Transcriptome Profiling of Dorsolateral Prefrontal Cortex: Mechanistic Roles for Neuronal Gene Expression, Including the 17q21.31 Locus, in PTSD Stress Response

American Journal of Psychiatry, Journal Year: 2023, Volume and Issue: 180(10), P. 739 - 754

Published: July 26, 2023

Objective: Multidisciplinary studies of posttraumatic stress disorder (PTSD) and major depressive (MDD) implicate the dorsolateral prefrontal cortex (DLPFC) in disease risk pathophysiology. Postmortem brain have relied on bulk-tissue RNA sequencing (RNA-seq), but single-cell RNA-seq is needed to dissect cell-type-specific mechanisms. The authors conducted first single-nucleus postmortem study PTSD elucidate transcriptomic pathology with resolution. Method: Profiling 32 DLPFC samples from 11 individuals PTSD, 10 MDD, control subjects was (∼415K nuclei; >13K cells per sample). A replication sample included 15 (∼160K >11K Results: Differential gene expression analyses identified significant differentially expressed genes (snDEGs) excitatory (EX) inhibitory (IN) neurons astrocytes, not other cell types or bulk tissue. MDD had more false discovery rate–corrected snDEGs, a greater rate. In EX IN neurons, biological pathways that were enriched compared glucocorticoid signaling. Furthermore, signaling induced pluripotent stem (iPSC)–derived cortical demonstrated relevance opposite direction regulation especially neurons. Many snDEGs 17q21.31 locus are particularly interesting given causal roles pathogenesis DLPFC-based neuroimaging (PTSD: ARL17B, LINC02210-CRHR1, LRRC37A2; MDD: LRRC37A LRP4), while others regulated by glucocorticoids iPSC-derived SLC16A6, TAF1C; CDH3). Conclusions: findings point mechanisms response highlighting importance examining indicating promising novel biomarkers therapeutic targets.

Language: Английский

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Biological Embedding of Early-Life Adversity and a Scoping Review of the Evidence for Intergenerational Epigenetic Transmission of Stress and Trauma in Humans

Genes, Journal Year: 2023, Volume and Issue: 14(8), P. 1639 - 1639

Published: Aug. 17, 2023

Severe or chronic stress and trauma can have a detrimental impact on health. Evidence suggests that early-life adversity become biologically embedded has the potential to influence health outcomes decades later. Epigenetics is one mechanism been implicated in these long-lasting effects. Observational studies humans indicate effects of could even persist across generations, although whether not epigenetic mechanisms are involved remains under debate. Here, we provide an overview animals demonstrate DNA methylation, most widely studied mechanisms, summarize findings from animal models demonstrating involvement epigenetics transmission generations. We then describe results scoping review determine extent which terms intergenerational transgenerational used human investigating via mechanisms. end with discussion key areas for future research advance understanding role legacy trauma.

Language: Английский

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Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts

Cell Reports, Journal Year: 2020, Volume and Issue: 31(9), P. 107716 - 107716

Published: June 1, 2020

To reveal post-traumatic stress disorder (PTSD) genetic risk influences on tissue-specific gene expression, we use brain and non-brain transcriptomic imputation. We impute genetically regulated expression (GReX) in 29,539 PTSD cases 166,145 controls from 70 ancestry-specific cohorts identify 18 significant GReX-PTSD associations corresponding to specific tissue-gene pairs. The results suggest substantial heterogeneity based ancestry, cohort type (military versus civilian), sex. Two study-wide are identified European military cohorts; ZNF140 is predicted be upregulated whole blood, SNRNP35 downregulated dorsolateral prefrontal cortex, respectively. In peripheral leukocytes 175 marines, the observed differential correlates with differences for these individuals, deployment produces glucocorticoid-regulated changes that include downregulation of both SNRNP35. knockdown cells validates its functional role U12-intron splicing. Finally, exogenous glucocorticoids mice downregulate Snrnp35 expression.

Language: Английский

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Emerging roles of non-coding RNAs in the pathogenesis, diagnosis and prognosis of osteosarcoma

Investigational New Drugs, Journal Year: 2018, Volume and Issue: 36(6), P. 1116 - 1132

Published: Aug. 6, 2018

Language: Английский

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Brain Trauma, Glucocorticoids and Neuroinflammation: Dangerous Liaisons for the Hippocampus

Biomedicines, Journal Year: 2022, Volume and Issue: 10(5), P. 1139 - 1139

Published: May 15, 2022

Glucocorticoid-dependent mechanisms of inflammation-mediated distant hippocampal damage are discussed with a focus on the consequences traumatic brain injury. The effects glucocorticoids specific neuronal populations in hippocampus depend their concentration, duration exposure and cell type. Previous stress elevated level prior to pro-inflammatory impact, as well long-term though moderate elevation glucocorticoids, may inflate effects. Glucocorticoid-mediated long-lasting circuit changes after trauma involved late post-traumatic pathology development, such epilepsy, depression cognitive impairment. Complex diverse actions hypothalamic-pituitary-adrenal axis neuroinflammation be essential for pathology. These applicable remote occurring other types focal (stroke, epilepsy) or central nervous system diseases without obvious Thus, liaisons excessive glucocorticoids/dysfunctional neuroinflammation, dangerous hippocampus, crucial many diseases. Taking into account that controls both functions emotional state, further research potential links between glucocorticoid signaling inflammatory processes respective is vital.

Language: Английский

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Alzheimer’s Disease-Related Epigenetic Changes: Novel Therapeutic Targets

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 61(3), P. 1282 - 1317

Published: Sept. 12, 2023

Language: Английский

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