Cellular bioenergetics changes in magnocellular neurons may affect copeptin expression in the late phase of sepsis

• Copeptin plays an important role in the correct structural formation of vasopressin.
• Increased hypothalamic IL-1β and NO levels cause bioenergetics changes.
• Apoptosis markers increased in magnocellular neurons during sepsis.
• Decreased copeptin expression compromising AVP synthesis and secretion in the sepsis.

We investigated whether inflammatory mediators during cecal ligation and puncture (CLP)-induced sepsis may diminish copeptin expression in magnocellular neurons, thus affecting arginine-vasopressin (AVP) synthesis. The transcript abundance of IL-1β, IL-1R1, iNOS and HIF-1α was continuously elevated. IL-1β, iNOS and cytochrome c protein levels progressively increased until 24 h. Immunostaining for these proteins was higher at 6 and 24 h, as also seen in the annexin-V assay, while copeptin was continuously decreased. This suggests that increased IL-1β and NO levels may cause significant bioenergetics changes in magnocellular neurons, affecting copeptin expression and compromising AVP synthesis and secretion in the late phase of sepsis.