Studies on the mechanisms for autonomic function regulation by Melanocortin-4 receptors

Abstract

Melanocortin-4 receptors (MC4Rs) regulate appetite and metabolism in the central nervous system. Loss-of-function mutation of MC4R results in hyperphagia, obesity, hyperinsulinemia, and decreased energy expenditure, both in human patients and model mice. As obese patients baring MC4R mutations are protected against hypertension, MC4Rs are regarded as a future key target for novel drug for obesity, diabetes, and hypertension. MC4Rs in the autonomic nervous system reciprocally regulate sympathetic and parasympathetic nervous system. A previous study revealed that MC4R agonist hyperpolarized neurons of the dorsal motor nucleus of the vagus nerve (DMV), whereas depolarized neurons of the intermediolateral cell column of the spinal cord (IML). However, detailed mechanism of MC4R action is still unknown. In this thesis, I studied detailed mechanisms of MC4R-mediated regulation of miniature postsynaptic currents in the autonomic nervous system with whole-cell patch clamp technique.