Substance P receptor activation induces downregulation of the AMPA receptor functionality in cortical neurons from a genetic model of Amyotrophic Lateral Sclerosis

► Substance P (SP) is able to reduce significantly in G93A cortical neurons the kainate-induced currents and the mEPSCs. ► The effect is blocked by GR 82334, a NK1 competitive antagonist of SP receptor. ► Western blot and immunocytochemistry analysis indicate a higher NK1 expression level in G93A compared to Control cultures. ► Toxicity experiments reveal that SP is able to rescue G93A cortical neurons to a greater extent than Control neurons. ► The indication of a protective role of SP in the G93A mouse suggests an use of SP as a clinical therapeutic treatment.