ausblenden:
Schlagwörter:
Energy metabolism, Nucleus accumbens, Anterior cingulate cortex, Posttraumatic stress disorder model, Fluoxetine
Zusammenfassung:
Posttraumatic stress disorder (PTSD) is a prevalent psychiatric
disorder. Several studies have attempted to characterize molecular
alterations associated with PTSD, but most findings were limited to the
investigation of specific cellular markers in the periphery or defined
brain regions. In the current study, we aimed to unravel affected
molecular pathways/mechanisms in the fear circuitry associated with
PTSD. We interrogated a foot shock-induced PTSD mouse model by
integrating proteomics and metabolomics profiling data. Alterations at
the proteome level were analyzed using in vivo (15)N metabolic labeling
combined with mass spectrometry in the prelimbic cortex (PrL), anterior
cingulate cortex (ACC), basolateral amygdala, central nucleus of the
amygdala and CA1 of the hippocampus between shocked and nonshocked
(control) mice, with and without fluoxetine treatment. In silico pathway
analyses revealed an upregulation of the citric acid cycle pathway in
PrL, and downregulation in ACC and nucleus accumbens (NAc). Chronic
fluoxetine treatment prevented decreased citric acid cycle activity in
NAc and ACC and ameliorated conditioned fear response in shocked mice.
Our results shed light on the role of energy metabolism in PTSD
pathogenesis and suggest potential therapy through mitochondrial
targeting.
