Decoding the transcriptomic signatures of psychological trauma in human cortex and amygdala

Опубликована: Окт. 23, 2024

Psychological trauma has profound effects on brain function and precipitates psychiatric disorders in vulnerable individuals, however, the molecular mechanisms linking with risk remain incompletely understood. Using RNA-seq data postmortem tissue of a cohort 304 donors (N=136 exposure), we investigated transcriptional signatures exposures two cortical regions (dorsolateral prefrontal cortex, dorsal anterior cingulate cortex) amygdala (medial basolateral amygdala) associated stress processing regulation. We focused dissecting heterogeneity traumatic experiences these by investigating exposure to several types (childhood, adulthood, complex, single acute, combat, interpersonal traumas) interactions sex. Overall, were more childhood traumas, whereas adulthood (regardless experience). cell-type-specific expression imputation, identified strong response medial excitatory neurons trauma, which coincided dysregulation observed human induced pluripotent stem cell (hiPSC)-derived glutamatergic exposed hydrocortisone. resolved multiscale coexpression networks for each region modules enriched whose connectivity was altered trauma. Trauma-associated provide insight into coordinated functional different traumas point potential gene targets further dissection. Together, characterization long-lasting encoding corticolimbic brain.

Язык: Английский

Single‐Nucleus RNA Sequencing Reveals That Gabra6⁺ Neurons in Prefrontal Cortex Promote the Progression of PTSD After Shockwave‐Induced TBI

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