Transcriptomic Evaluation of a Stress Vulnerability Network Using Single-Cell RNA Sequencing in Mouse Prefrontal Cortex.

BACKGROUND: Increased vulnerability to stress is a major risk factor for several mood disorders, including major depressive disorder. Although cellular and molecular mechanisms associated with depressive behaviors following stress have been identified, little is known about the mechanisms that confer the vulnerability that predisposes individuals to future damage from chronic stress. METHODS: We used multisite in vivo neurophysiology in freely behaving male and female C57BL/6 mice (n = 12) to measure electrical brain network activity previously identified as indicating a latent stress vulnerability brain state. We combined this neurophysiological approach with single-cell RNA sequencing of the prefrontal cortex to identify distinct transcriptomic differences between groups of mice with inherent high and low stress vulnerability. RESULTS: We identified hundreds of differentially expressed genes (padjusted < .05) across 5 major cell types in animals with high and low stress vulnerability brain network activity. This unique analysis revealed that GABAergic (gamma-aminobutyric acidergic) neuron gene expression contributed most to the network activity of the stress vulnerability brain state. Upregulation of mitochondrial and metabolic pathways also distinguished high and low vulnerability brain states, especially in inhibitory neurons. Importantly, genes that were differentially regulated with vulnerability network activity significantly overlapped (above chance) with those identified by genome-wide association studies as having single nucleotide polymorphisms significantly associated with depression as well as genes more highly expressed in postmortem prefrontal cortex of patients with major depressive disorder. CONCLUSIONS: This is the first study to identify cell types and genes involved in a latent stress vulnerability state in the brain.

Persistence of 2,4,6-triamino-1,3,5-trinitrobenzene in the environment.

2,4,6-triamino-1,3,5-trinitrobenzene (TATB) is an Insensitive High Explosive (IHE) that is increasingly being used as a safer alternative to traditional energetic materials. However, the high thermal stability of TATB poses challenges for its disposal, particularly through existing open burning methods and its ability to remain in the environment for long period of time. Therefore, this study investigated the persistence of TATB in the environment by conducting small-scale experiments which were designed to examine the resistance of TATB to open burning and to assess unburnt residues. To evaluate the fate and transport of the unburnt materials in soil, laboratory-scale soil column transport studies were conducted to gauge the movement of TATB through soil. The results indicate that TATB exhibits a high resistance to burning, leaving unburnt materials that can persist in soil. The study emphasizes the importance of efficient disposal methods for explosives and highlights the need for further research to understand the environmental impact and toxicity of TATB.