Spreading depression activates unfolded protein response.

Preconditioning is a process where a preceding non-lethal form of stress activates a stress response that protects cells against an otherwise lethal form of stress. Preconditioning can be induced in various ways including short-term ischemia or spreading depression. Here we investigated the effect of 1 h repetitive spreading depression on the unfolded protein response (UPR), a stress response activated under conditions associated with endoplasmic reticulum (ER) dysfunction. Spreading depression induced processing of xbp1 mRNA, indicative of an activation of UPR. Processing of xbp1 was paralleled by a rise in grp78 mRNA levels resulting from an activation of a signal transduction pathway that depends on protein synthesis. Preconditioning-induced activation of UPR may preserve ER functioning under pathological conditions interfering with ER functions.