Role of Sex Hormones in Regulation of Sodium-Proton Exchanger NHE1: Implications for Migraine

Migraine is the most common neurological disorder, affecting approximately 11% of the world population. Because women comprise over 75% of the migraineur population, female reproductive hormones, namely estrogen, are thought to play a crucial role in this debilitating disease. Preclinical studies have demonstrated that estrogen increases susceptibility to an electrical phenomenon in the brain called cortical spreading depression (CSD), which is theorized to be associated with migraine with aura; however, its mechanism is unknown. Dysregulation of pH in the brain is also known to occur in CSD and potentially aura, however it is unknown if estrogen influences brain pH. NHE1 is a ubiquitously expressed Na+/H+ exchanger involved in maintaining cellular pH. Both increases and decreases in NHE1 expression may affect neuronal excitability and meningeal nociception, which have implications in migraine. In vivo studies in Sprague-Dawley rats were conducted to compare NHE1 expression in male and female rat whole-br...