Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post-traumatic stress disorder

ABSTRACT: A social-stress mouse model, involving exposure of an intruder (male C57BL/6) mouse to a resident aggressor (male SJL) mouse followed by exposure to trauma reminders with post-trauma periods, was used to simulate features of human PTSD.  Transcriptome changes in blood, brain regions and spleen, and DNA methylome changes in hemi-brain of aggressor-exposed and control C57BL/6 mice were assayed at one, 10 and 42 days of post-trauma periods. Assessments of activation patterns for differentially expressed transcripts (overlapping among hemi-brain, blood and spleen), and differentially methylated promoter regions showed increased activations of inflammatory pathways, and inhibited pathways related to neurogenesis and synaptic plasticity at longer post-trauma days.  In amygdala, hippocampus and medial pre-frontal cortext, these pathways were activated at earlier post-trauma periods. But at longer post-trauma periods, neurogenesis and synaptic plasticity were inhibited while lower level of activated inflammation persisted in hippocampus and medial pre-frontal cortex.  Pathways implicated in diabetes, insulin signaling, metabolic disorder, mitochondrial dysfunctions, circadian disruption, oxidative stress and inhibited telomere maintenance were significantly enriched.  Identification of brain – blood overlapping molecular signatures provide increased confidence in using blood as brain surrogate sample for clinical translation. Our findings suggest that stress-induced inflammation triggers impaired neurogenesis, cognitive decline, and chronic pain (physical complaints in PTSD patients).  Signaling pathways implicated in neurogenesis and synaptic plasticity seem to be mediating the effect of neuroinflammation in the development and maintenance of behavioral manifestations of PTSD.  While inflammation seems to be directly involved in tissue damage triggering, exacerbating or maintaining the somatic comorbid pathologies of PTSD.

ORGANISM(S): Mus musculus

PROVIDER: GSE85495 | GEO | 2017/08/31

SECONDARY ACCESSION(S): PRJNA338744

REPOSITORIES: GEO