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Free keywords:
Inflammatory pathways, Anterior cingulate cortex, PTSD model, Fluoxetine
Abstract:
Despite intense research efforts the molecular mechanisms affecting
stress-vulnerable brain regions in posttraumatic stress disorder (PTSD)
remain elusive. In the current study we have applied global
transcriptomic profiling to a PTSD mouse model induced by foot shock
fear conditioning. We compared the transcriptomes of prelimbic cortex,
anterior cingulate cortex (ACC), basolateral amygdala, central nucleus
of amygdala, nucleus accumbens (NAc) and CAI of the dorsal hippocampus
between shocked and non shocked (control) mice, with and without
fluoxetine treatment by RNA sequencing. Differentially expressed (DE)
genes were identified and clustered for in silico pathway analysis.
Findings in relevant brain regions were further validated with
immunohistochemistry. DE genes belonging to 11 clusters were identified
including increased inflammatory response in ACC in shocked mice. In
line with this finding, we noted higher microglial activation in ACC of
shocked mice. Chronic fluoxetine treatment initiated in the aftermath of
the trauma prevented inflammatory gene expression alterations in ACC and
ameliorated PTSD-like symptoms, implying an important role of the immune
response in PTSD pathobiology. Our results provide novel insights into
molecular mechanisms affected in PTSD and suggest therapeutic
applications with anti-inflammatory agents. (C) 2016 Elsevier Ltd. All
rights reserved.
