Transcriptome profiling of spleen, blood and hemi-brain of social stressed C57B6 mice exhibiting PTSD like features
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ABSTRACT: Social stress mouse models were used to simulate human post-traumatic stress disorder (PTSD). C57B/6 mice exposed to SJL aggressor mice exhibited behaviors accepted as PTSD-in-mouse phenotype: 'frozen' motion, aggressor's barrier avoidance, startled jumping, and retarded locomotion. Transcripts in spleen, blood and hemi-brain of stressed and control C57B/6 mice were analyzed using Agilent's mouse genome-wide arrays. C57B6 mice were exposed to SJL aggressor mice for periods of 5 days and 10 days (6 hours each day) to induce anxiety/stress which parallels to PTSD in human. Organs, blood and brain regions were collected after 24 hours and 1.5 week of post 5 days social defeat period; and 24 hour and 6 weeks post 10 days social stress period.
Project description:Social stress mouse models were used to simulate human post-traumatic stress disorder (PTSD). C57B/6 mice exposed to SJL aggressor mice exhibited behaviors accepted as PTSD-in-mouse phenotype: 'frozen' motion, aggressor’s barrier avoidance, startled jumping, and retarded locomotion. Transcripts in hippocampus, amygdala, medial prefrontal cortex, ventral striatum (nucleus acumbens), septal region, corpus striatum, hemi-brain, blood, spleen and heart of stressed and control C57B/6 mice were analyzed using Agilent’s mouse genome-wide arrays. C57B6 mice were exposed to SJL aggressor mice for periods of 5 days and 10days (6 hours each day) to induce anxiety/stress which parallels to PTSD in human Organs, blood and brain regions were collected after 24 hours and 1.5 week of post 5 days social defeat period; and 24 hour and 6 weeks post 10 days social stress period.
Project description:Social stress mouse models were used to simulate human post-traumatic stress disorder (PTSD). C57B/6 mice exposed to SJL aggressor mice exhibited behaviors accepted as PTSD-in-mouse phenotype: 'frozen' motion, aggressor's barrier avoidance, startled jumping, and retarded locomotion. Transcripts in spleen, blood and hemi-brain of stressed and control C57B/6 mice were analyzed using Agilent's mouse genome-wide arrays.
Project description:Social stress mouse models were used to simulate human post-traumatic stress disorder (PTSD). C57B/6 mice exposed to SJL aggressor mice exhibited behaviors accepted as PTSD-in-mouse phenotype: 'frozen' motion, aggressor’s barrier avoidance, startled jumping, and retarded locomotion. Transcripts in hippocampus, amygdala, medial prefrontal cortex, ventral striatum (nucleus acumbens), septal region, corpus striatum, hemi-brain, blood, spleen and heart of stressed and control C57B/6 mice were analyzed using Agilent’s mouse genome-wide arrays.
Project description:We have used a social defeat (SD) mouse model of post-traumatic stress disorder (PTSD) that is based on a brief exposure of a mouse to the aggressor mice for either 5 d or 10 d stress periods. Mice simulating aspects of posttraumatic stress disorder exhibit behavioral changes, body weight gain, increased body temperature, and inflammatory and fibrotic histopathologies and transcriptomic changes of heart tissue. Liver tissue of these mice was subjected to mRNA analysis. Transcriptomic analysis of liver indicated chronic toxicities and metabolic alterations in aggressor-exposed mice that possibly contributed to the persistent metabolic disturbance Two-condition experiment, C57BL6/J mice Biological replicates: 4-6 control replicates, 5-6 stressed replicates.
Project description: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.
Project description:We have used a social defeat (SD) mouse model of post-traumatic stress disorder (PTSD) that is based on a brief exposure of a mouse to the aggressor mice for either 5 d or 10 d stress periods. Mice simulating aspects of posttraumatic stress disorder exhibit behavioral changes, body weight gain, increased body temperature, and inflammatory and fibrotic histopathologies and transcriptomic changes of heart tissue. Liver tissue of these mice was subjected to mRNA analysis. Transcriptomic analysis of liver indicated chronic toxicities and metabolic alterations in aggressor-exposed mice that possibly contributed to the persistent metabolic disturbance
Project description:Using a PTSD mouse model, we investigated the longitudinal transcriptomic changes in heart tissues after the exposure to stress through intimidation We designed our initial study (Study I) with four experimental conditions where we varied the length of time that subservient mice were exposed to aggressor mice and the length of rest time after the exposure. The conditions included were short exposure-short rest (T5R1-T indicates the number of days of trauma exposure; R indicates the number of days of rest after exposure), short exposure-long rest (T5R10), long exposure-short rest (T10R1) and long exposure-long rest (T10R42)
Project description:Using a PTSD mouse model, we investigated the longitudinal transcriptomic changes in heart tissues after the exposure to stress through intimidation We designed our initial study (Study I) with four experimental conditions where we varied the length of time that subservient mice were exposed to aggressor mice and the length of rest time after the exposure. The conditions included were short exposure-short rest (T5R1-T indicates the number of days of trauma exposure; R indicates the number of days of rest after exposure), short exposure-long rest (T5R10), long exposure-short rest (T10R1) and long exposure-long rest (T10R42)
Project description:Using a PTSD mouse model, we investigated the longitudinal transcriptomic changes in heart tissues after the exposure to stress through intimidation We designed our time-course study (Study II) with three experimental conditions where we varied the length of time that subservient mice were exposed to aggressor mice with the same length of rest time after the exposure (1day). The conditions included were 1day-exposure (T1R1), 2day-exposure (T2R1) and 3day-exposure (T3R1). We designed our initial study (Study I) with four experimental conditions where we varied the length of time that subservient mice were exposed to aggressor mice and the length of rest time after the exposure. The conditions included were short exposure-short rest (T5R1-T indicates the number of days of trauma exposure; R indicates the number of days of rest after exposure), short exposure-long rest (T5R10), long exposure-short rest (T10R1) and long exposure-long rest (T10R42)
Project description:Using a PTSD mouse model, we investigated the longitudinal transcriptomic changes in heart tissues after the exposure to stress through intimidation We designed our time-course study (Study II) with three experimental conditions where we varied the length of time that subservient mice were exposed to aggressor mice with the same length of rest time after the exposure (1day). The conditions included were 1day-exposure (T1R1), 2day-exposure (T2R1) and 3day-exposure (T3R1).