Shared and unique transcriptional changes in the orbitofrontal cortex in psychiatric disorders and suicide

Mon, 29 Jan 2024 00:00:00 +0000

Psychiatric disorders like major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BPD), represent a significant global public health concern. Sex differences in the prevalence and presentation of psychiatric disorders, and the association of a psychiatric diagnosis with increased risk of suicide, are well-established. However, the neurobiology underlying these features of disease are not well understood. Dysfunction of the orbitofrontal cortex (OFC), a brain region responsible for decision-making and sensory processing, has been implicated in psychiatric disorders but remains understudied compared to other frontocortical brain regions.

In this study we investigated sexual dimorphism in psychiatric illnesses and suicide by analyzing publicly available OFC transcriptional profiles (RNAseq data obtained from the Stanley Neuropathology Consortium) from individuals with SCZ, BPD, MDD, and non-psychiatric controls (n=15/group).

Gene set enrichment analysis (GSEA) revealed significant differences in immune-related processes in male and female comparisons and in psychiatric disorders relative to controls. Analysis of top differentially expressed genes found changes in P2RY12 in males and females who died by suicide. Additionally, downregulation of protein folding processes was observed in female suicide subjects, suggesting an association between dysregulated protein metabolism and suicide. Our results further our understanding of the shared and unique molecular pathways underlying psychiatric disorders and suicide.

Probiotic Protects Kidneys Exposed to Microcystin-LR

Mon, 29 Jan 2024 00:00:00 +0000

Cyanobacterial Harmful Algal Blooms (CyanoHABs) occur when colonies of photosynthetic bacteria called cyanobacteria grow out of control, usually in warm, nutrient-rich, slow-moving waters. They are becoming increasingly prevalent around the world and release harmful toxins called cyanotoxins into bodies of water, which negatively affect human and ecological health. One such cyanotoxin is microcystin, with microcystin-leucine arginine (MC-LR) being the most widespread. Exposure to MC-LR inhibits serine and threonine protein phosphatase 1 and 2A in humans, causing a myriad of health problems. Fortunately, certain naturally occurring bacteria may be able to degrade MC-LR and reverse its effects. Mice were separated into five experimental groups based on three types of pre-treatments (control drinking water/vehicle, probiotic-supplemented drinking water, and heat-inactivated probiotic-supplemented drinking water) as well as two types of exposures (microcystin-LR and water/vehicle). RNA was extracted from kidneys for sequencing because MC-LR exacerbates kidney disease. Gene expression data were analyzed with 3 Pod Reports, an R package that produces a three-part report consisting of Gene Set Enrichment Analysis (GSEA), EnrichR, and integrative LINCS (iLINCS). MC-LR exposure was associated with upregulated cellular respiration and metabolism pathways and downregulated transcription pathways. Probiotic pre-treatment combined with MC-LR exposure was associated with upregulated lipoprotein particle pathways and downregulated respiration and ribosome pathways. Overall, the probiotic mixture corrected the transcriptional profile resulting from MC-LR exposure. Future high yield pathways that could be targeted for therapeutic benefit include VEGFR inhibitors and increased expression of renal kidney indicator genes such as EGFR.

Translation: The University of Toledo Journal of Medical Sciences

Shared and unique transcriptional changes in the orbitofrontal cortex in psychiatric disorders and suicide

Probiotic Protects Kidneys Exposed to Microcystin-LR