Single‐Nucleus RNA Sequencing Reveals That Gabra6+ Neurons in Prefrontal Cortex Promote the Progression of PTSD After Shockwave‐Induced TBI DOI Creative Commons
Xiaowei Fei,

Zehan Zhang,

Yanan Dou

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 12, 2024

Abstract Shockwave‐induced traumatic brain injury (TBI) results in the onset of post‐traumatic stress disorder (PTSD), triggered either by TBI itself or other stressors. However, interplay and underlying mechanisms how these factors synergistically induce PTSD remain inadequately elucidated. Here, mice (induced biological shock tube blast injury) single prolonged method) groups both displayed symptoms behaviors, with TBI+PTSD (composite model) group exhibiting more severe manifestations. The result snRNA‐seq demonstrated a noticeable increase population Gabra6 + neurons prefrontal cortex region group. Knocking down cortical mitigated PTSD‐related behavioral outcomes. Mechanistically, Smad3/4 complex activation led to upregulation expression neurons. Interaction Homer1 activated downstream cAMP signaling pathways. KO‐Nestin show reduced susceptibility PTSD. Subsequently, efficacy monoclonal antibody intervention at 218 site ameliorating development is verified. This study suggests that stressors act as independent components development, pivotal facilitating formation. Strategies geared toward minimizing exposure singular combined may effectively diminish risk developing

Язык: Английский

A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex DOI
Louise A. Huuki-Myers, Abby Spangler, Nicholas J. Eagles

и другие.

Science, Год журнала: 2024, Номер 384(6698)

Опубликована: Май 23, 2024

The molecular organization of the human neocortex historically has been studied in context its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification transcriptionally defined domains that move beyond classic cytoarchitecture. We used Visium gene expression platform to generate a data-driven neuroanatomical atlas across anterior-posterior axis dorsolateral prefrontal cortex. Integration with paired single-nucleus RNA-sequencing data revealed distinct cell type compositions and cell-cell interactions domains. Using PsychENCODE publicly available data, we mapped enrichment types genes associated neuropsychiatric disorders discrete

Язык: Английский

Процитировано

19
Stress System Concordance: A Signature of Resilience DOI Creative Commons
E. R. de Kloet, Marc L. Molendijk

Biological Psychiatry Global Open Science, Год журнала: 2025, Номер 5(1), С. 100427 - 100427

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Stress-induced changes in the molecular processes underlying fear memories: implications for PTSD and relevant animal models DOI Creative Commons
Raül Andero

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

Процитировано

0
AI as an accelerator for defining new problems that transcends boundaries DOI Creative Commons
Tayo Obafemi-Ajayi,

Steven Jennings,

Yu Zhang

и другие.

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

Процитировано

0
The evolving neurobiology of early-life stress DOI Creative Commons
Matthew T. Birnie, Tallie Z. Baram

Neuron, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Corticosteroid‐regulated gene transcription in SH‐SY5Y‐derived neurons: Insights into the mineralocorticoid and glucocorticoid receptor‐mediated response DOI Open Access

Justina F. Lugenbühl,

Clara Snijders,

Cameron D. Pernia

и другие.

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

Процитировано

0
Epigenetic factors in posttraumatic stress disorder resilience and susceptibility DOI Creative Commons
Majeed M. A. Ali,

Ibrahim El Tantawy El Sayed,

Yuliang Wang

и другие.

Egyptian Journal of Medical Human Genetics, Год журнала: 2025, Номер 26(1)

Опубликована: Март 20, 2025

Abstract Background Posttraumatic stress disorder (PTSD) affects approximately 8% of the US population, with varying susceptibility among individuals exposed to trauma. While genetic factors contribute PTSD risk, emerging evidence suggests that epigenetic mechanisms play a crucial role in translating environmental exposures into lasting neurobiological changes. Purpose This review provides comprehensive analysis cutting-edge research on PTSD, particular emphasis novel findings regarding resilience and mechanisms. We explore recent technological advances their applications understanding pathophysiology. Main body Advanced epigenomic approaches have revealed complex interactions between DNA methylation, histone modifications, non-coding RNAs PTSD. Novel highlight cell type-specific signatures temporal dynamics following trauma exposure. Single-cell studies identified previously unknown cellular heterogeneity responses. Recent data modifications not only influence individual but may also transgenerational transmission effects. Integrative multi-omics new insights molecular networks underlying vulnerability. Conclusion unprecedented complexity These open avenues for personalized interventions based profiles suggest therapeutic strategies targeting modifications. enhanced has significant implications risk assessment, prevention, treatment. Graphical abstract

Язык: Английский

Процитировано

0
Designing clinical trials for an inflammatory subtype of major depression DOI
Andrew H. Miller, Jennifer C. Felger, Ebrahim Haroon

и другие.

Biological Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Transcriptomic analysis of the human habenula in schizophrenia DOI Creative Commons
Ege A Yalcinbas, Bukola Ajanaku, Erik D. Nelson

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 27, 2024

Abstract Pathophysiology of many neuropsychiatric disorders, including schizophrenia (SCZD), is linked to habenula (Hb) function. While pharmacotherapies and deep brain stimulation targeting the Hb are emerging as promising therapeutic treatments, little known about cell type-specific transcriptomic organization human or how it altered in SCZD. Here we define molecular neuroanatomy identify changes individuals with SCZD compared neurotypical controls. Utilizing Hb-enriched postmortem tissue, performed single nucleus RNA-sequencing (snRNA-seq; n=7 donors) identified 17 molecularly defined types across 16,437 nuclei, 3 medial 7 lateral populations, several which were conserved between rodents humans. Single molecule fluorescent situ hybridization (smFISH; n=3 validated snRNA-seq mapped their spatial locations. Bulk type deconvolution tissue from 35 33 controls yielded 45 SCZD-associated differentially expressed genes (DEGs, FDR < 0.05), 32 (71%) unique tissue. eQTL analysis 717 independent SNP-gene pairs (FDR where either SNP a risk variant (16 pairs) gene DEG (7 pairs). colocalization 16 colocalized genes. These results topographically organized distinct signatures demonstrate genetic associated SCZD, thereby providing novel insights into role disorders. One Sentence Summary Transcriptomic identification illness state.

Язык: Английский

Процитировано

4
Regulation of Stress-Induced Immunosuppression in the Context of Neuroendocrine, Cytokine, and Cellular Processes DOI Creative Commons
Evgenii I. Balakin, Kseniya A. Yurku, M. V. Ivanov

и другие.

Biology, Год журнала: 2025, Номер 14(1), С. 76 - 76

Опубликована: Янв. 15, 2025

Understanding the regulatory mechanisms of stress-induced immunosuppression and developing reliable diagnostic methods are important tasks in clinical medicine. This will allow for development effective strategies prevention treatment conditions associated with immune system dysfunction induced by chronic stress. The purpose this review is to conduct a comprehensive analysis synthesis existing data on immunosuppression. aimed at identifying key neuroendocrine, cytokine, cellular processes underlying suppression response under study involved search scientific literature covering cellular, molecular regulation, as well modern its diagnosis. Major international bibliographic databases publications biomedicine, psychophysiology, immunology were selected search. results identified regulating reviewed provided detailed descriptions neuroendocrine cytokine A significant portion confirms that activation hypothalamic-pituitary-adrenal (HPA) axis subsequent elevation cortisol levels exert substantial immunosuppressive effects cells, particularly macrophages lymphocytes, leading innate adaptive responses. also highlight crucial role catecholamines (adrenaline noradrenaline) initiating

Язык: Английский

Процитировано

0