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Repurposing Citicoline for single prolonged stress-induced behavioral and hippocampal molecular abnormalities in male mice: Novel mechanistic attenuation of endoplasmic reticulum stress, mitochondrial

3 hours ago
  • #Mitophagy
  • #Citicoline
  • #PTSD
  • The study investigated repurposing citicoline for PTSD-like symptoms in male mice exposed to single prolonged stress (SPS).
  • Citicoline reversed SPS-induced behavioral deficits in social novelty preference, marble burying, and cue-induced freezing.
  • Molecularly, citicoline attenuated endoplasmic reticulum stress by modulating unfolded protein response components (e.g., reducing phosphorylated PERK, ATF4, ATF6).
  • It enhanced protective mitophagy via increased PTEN-induced kinase 1 and parkin expression, aiding clearance of damaged mitochondria and reactive oxygen species.
  • Citicoline reduced oxidative stress by lowering lipid peroxidation and restoring glutathione levels.
  • It promoted mitochondrial biogenesis via upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and inhibited apoptosis by suppressing caspase-3.