Stress and the brain transcriptome: Identifying commonalities and clusters in standardized data from published experiments

Prog Neuropsychopharmacol Biol Psychiatry. 2022 Dec 20:119:110558. doi: 10.1016/j.pnpbp.2022.110558. Epub 2022 Apr 8.

Abstract

Interpretation of transcriptomic experiments is hindered by many problems including false positives/negatives inherent to big-data methods and changes in gene nomenclature. To find the most consistent effect of stress on brain transcriptome, we retrieved data from 79 studies applying animal models and 3 human studies investigating post-traumatic stress disorder (PTSD). The analyzed data were obtained either with microarrays or RNA sequencing applied to samples collected from more than 1887 laboratory animals and from 121 human subjects. Based on the initial database containing a quarter million differential expression effect sizes representing transcripts in three species, we identified the most frequently reported genes in 223 stress-control comparisons. Additionally, the analysis considers sex, individual vulnerability and contribution of glucocorticoids. We also found an overlap between gene expression in PTSD patients and animals which indicates relevance of laboratory models for human stress response. Our analysis points to genes that, as far as we know, were not specifically tested for their role in stress response (Pllp, Arrdc2, Midn, Mfsd2a, Ccn1, Htra1, Csrnp1, Tenm4, Tnfrsf25, Sema3b, Fmo2, Adamts4, Gjb1, Errfi1, Fgf18, Galnt6, Slc25a42, Ifi30, Slc4a1, Cemip, Klf10, Tom1, Dcdc2c, Fancd2, Luzp2, Trpm1, Abcc12, Osbpl1a, Ptp4a2). Provided transcriptomic resource will be useful for guiding the new research.

Keywords: Brain; Glucocorticoids; PTSD; Resistance; Sex; Stress; Transcriptome; Vulnerability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • DNA-Binding Proteins / metabolism
  • High-Temperature Requirement A Serine Peptidase 1 / genetics
  • High-Temperature Requirement A Serine Peptidase 1 / metabolism
  • Humans
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism
  • Stress Disorders, Post-Traumatic* / metabolism
  • TRPM Cation Channels* / genetics
  • TRPM Cation Channels* / metabolism
  • Transcriptome

Substances

  • DNA-Binding Proteins
  • LUZP2 protein, human
  • TRPM Cation Channels
  • TRPM1 protein, human
  • PTP4A2 protein, human
  • Protein Tyrosine Phosphatases
  • High-Temperature Requirement A Serine Peptidase 1
  • HTRA1 protein, human