Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 1, 2024
Language: Английский
Cell, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Citations
3
Nature, Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 11, 2024
Language: Английский
Citations
8
Science Advances, Journal Year: 2025, Volume and Issue: 11(7)
Published: Feb. 14, 2025
Disruptions in the tightly regulated process of human brain development have been linked to increased risk for and mental illnesses. While genetic contribution these diseases is well established, important environmental factors less studied at molecular cellular levels. Here, we used single-cell cell type-specific techniques investigate effect glucocorticoid (GC) exposure, a mediator antenatal risk, on gene regulation lineage specification unguided neural organoids. We characterized transcriptional response chronic GC exposure during differentiation underlying regulatory networks by integrating transcriptomics with chromatin accessibility data. found lasting changes that included autism genes several transcription associated neurodevelopment. Chronic influenced primarily priming inhibitory neuron through like PBX3. provide evidence convergence common mechanism altering specification.
Language: Английский
Citations
1
Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(8), P. 519 - 534
Published: July 1, 2024
Language: Английский
Citations
5
Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)
Published: April 10, 2024
Biological sex is a key variable influencing many physiological systems. Disease prevalence as well treatment success can be modified by sex. Differences emerge already early in life and include pregnancy complications adverse birth outcomes. The placenta critical organ for fetal development shows sex-based differences the expression of hormones cytokines. Epigenetic regulation, such DNA methylation (DNAm), may underlie previously reported placental sexual dimorphism. We associated DNAm with three cohorts. Individual cohort results were meta-analyzed random-effects modelling. CpG-sites differentially methylated further investigated regarding pathway enrichment, overlap quantitative trait loci (meQTLs), hits from phenome-wide association studies (PheWAS). evaluated consistency findings across tissues (CVS, i.e. chorionic villus sampling placenta, cord blood) gene expression. identified 10,320 epigenome-wide significant sex-differentially probes (DMPs) spread throughout epigenome at birth. Most DMPs presented lower levels females. mapped to genes upregulated brain, enriched neurodevelopmental pathways significantly overlapped meQTLs PheWAS hits. Effect sizes moderately correlated between CVS birth, but only weakly blood. Sex differential was less pronounced implicated genetic regions marginally those DNAm. Our study provides an integrative perspective on sex-differential perinatal underscoring possible link brain.
Language: Английский
Citations
3
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: June 26, 2024
Abstract Human Accelerated Regions (HARs) are highly conserved across species but exhibit a significant excess of human-specific sequence changes, suggesting they may have gained novel functions in human evolution. HARs include transcriptional enhancers with activity and been implicated the evolution brain. However, our understanding how contributed to uniquely features brain is hindered by lack insight into genes pathways that regulate. It unclear whether acted altering expression gene targets between their chimpanzee orthologs or gaining new human, mechanism termed enhancer hijacking. We generated high-resolution map chromatin interactions for 1,590 neural stem cells (NSCs) comprehensively identify both species. targeted set 2,963 enriched neurodevelopmental processes including neurogenesis synaptic transmission. Changes HAR were correlated changes target expression. Conserved among differentially expressed NSCs non-human primate developing adult Species-specific did not converge on known biological significantly genes, alter via targets, also showed cell type-specific patterns brain, outer radial glia, which hypothesized contribute cortical expansion. Our findings support influenced provide means functionally link features.
Language: Английский
Citations
3
Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 1, 2024
Language: Английский
Citations
3
Journal of Thrombosis and Thrombolysis, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 15, 2025
Abstract Some patients with large vessel occlusion (LVO) achieve insufficient clinical improvement (futile recanalization, FR) after intravenous thrombolysis (IVT) during inter-hospital transfer for thrombectomy, while others show good outcomes (effective ER). This study assessed FR and ER rates among treated IVT at non-thrombectomy primary stroke centers (PSCs) aimed to identify predictors of FR. We analyzed data from two PSC registries (2016–2022). Inclusion criteria: treatment, anterior circulation LVO, NIHSS ≥ 6, ASPECTS 5, documented recanalization thrombectomy centers. was defined as a 90-day poor outcome (mRS 3–6) despite LVO on initial angiography. Among 190 post-IVT, 113 (59.5%) had Multivariable analysis identified age (OR = 1.03, 95%CI 1.01–1.07, p 0.021), the 1.13, 1.05–1.22, 0.026), collateral status 0.54, 0.39–0.75, 0.001) independent mortality. A model combining age, NIHSS, score provided highest predictive accuracy is common in LVO-related ischemic Identifying can guide clinicians early decision-making, allowing tailored interventions informed discussions about expected outcomes, potentially leading more optimized patient management. The GOTIC-VTE trial Unique identifier, jRCTs031180124; Registration date, April 06, 2017. Graphical
Language: Английский
Citations
0
Journal of Neuroendocrinology, Journal Year: 2025, Volume and Issue: unknown
Published: March 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.
Language: Английский
Citations
0
Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)
Published: May 9, 2025
Language: Английский
Citations
0