Systems Biology Application to Studies of Post Traumatic Stress Disorder (57251LS)
Final rept. 14 Sep 2009-13 Sep 2011
GENEVA FOUNDATION LAKEWOOD WA
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We evaluated a mouse model of multiple aggressor encounters for features of PTSD. Three different strains of subject mice C57BL6, DBA2 and BALBc were exposed to a trained aggressor mouse for 1 to 3 random sessions per day for 5 or 10 days using a cage-in-cage resident-intruder protocol behavioral, physiological, histological, gene expression, and metabolomic parameters were assessed. Subject mice exhibited fewer territorial behaviors reduced urine marking and exploration, weight gain, and increased body temperature, cardiac multifocal vasculitis and myocarditis, spleen morphological changes, and reduced dendritic spine density in the medial prefrontal cortex. Altered behaviors included avoidance of the aggressor and decreased motor activity when near the aggressor, and escape and fighting back that differed among mouse strains. More intense behavioral changes resulted from longer stress. Recovery to control behaviors was incomplete by 4 weeks but complete after 6 weeks of home cage rest. Global metabolic profiling of stressed mouse plasma detected 496 small molecules 330 known and 166 unknown whose altered levels indicate changes in neurotransmitters, redox status, neuronal damage, and energetics suggestive of metabolic syndrome. Ongoing analyses of stress-induced transcriptome changes in mouse brain and human and mouse leukocytes aims to identify common biomarkers of the diseased state.
- Medicine and Medical Research