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

• Published in: Translational psychiatry 2017-05, Vol.7 (5), p.e1135-e1135
• Main Authors: Muhie, S, Gautam, A, Chakraborty, N, Hoke, A, Meyerhoff, J, Hammamieh, R, Jett, M
• Format: Article
• Language: English
• Subjects: 631/378/340; 631/477; 692/699/476; Amygdala - metabolism; Animals; Behavioral Sciences; Behavioral Symptoms - metabolism; Biological Psychology; Brain - metabolism; Brain - pathology; Disease Models, Animal; Hippocampus - metabolism; Inflammation - blood; Inflammation - metabolism; Male; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Neurogenesis; Neurogenesis - genetics; Neurogenesis - physiology; Neuronal Plasticity - genetics; Neuronal Plasticity - physiology; Neurosciences; Original; original-article; Pharmacotherapy; Post traumatic stress disorder; Prefrontal Cortex - metabolism; Psychiatry; Stress Disorders, Post-Traumatic - genetics; Stress, Psychological - metabolism; Transcriptome - genetics
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/tp.2017.91

A social-stress mouse model was used to simulate features of post-traumatic stress disorder (PTSD). The model involved exposure of an intruder (male C57BL/6) mouse to a resident aggressor (male SJL) mouse for 5 or 10 consecutive days. Transcriptome changes in brain regions (hippocampus, amygdala, medial prefrontal cortex and hemibrain), blood and spleen as well as epigenome changes in the hemibrain were assayed after 1- and 10-day intervals following the 5-day trauma or after 1- and 42-day intervals following the 10-day trauma. Analyses of differentially expressed genes (common among brain, blood and spleen) and differentially methylated promoter regions revealed that neurogenesis and synaptic plasticity pathways were activated during the early responses but were inhibited after the later post-trauma intervals. However, inflammatory pathways were activated throughout the observation periods, except in the amygdala in which they were inhibited only at the later post-trauma intervals. Phenotypically, inhibition of neurogenesis was corroborated by impaired Y-maze behavioral responses. Sustained neuroinflammation appears to drive the development and maintenance of behavioral manifestations of PTSD, potentially via its inhibitory effect on neurogenesis and synaptic plasticity. By contrast, peripheral inflammation seems to be directly responsible for tissue damage underpinning somatic comorbid pathologies. Identification of overlapping, differentially regulated genes and pathways between blood and brain suggests that blood could be a useful and accessible brain surrogate specimen for clinical translation.