Physiological roles of redox signals in relation to synaptic plasticity and brain functions

Abstract

In our classical knowledge, redox molecules, including reactive oxygen species (ROS), nitric oxide (NO) and hydrogen sulfide, are considered to be generated as byproducts of aerobic metabolism and act as harmful oxidants of macromolecules, such as proteins and lipids. On the other hands, recently, expressions of enzymes producing redox molecules are identified and reported to be expressed in wide range of tissues, including brain. Moreover, activities of some of these enzymes are revealed to be regulated by physiological signals (e.g. calcium). These observations suggest that redox molecules act as physiological messengers and have biological functions. Actually, recent studies indicate possible involvement of redox signals in functional modification of proteins essential for synaptic plasticity in cultured cells and acute slice preparations. For example, S-nitrosylation of type 1 ryanodine receptor, an intracellular calcium-release channel, is revealed to be essential for NO-induced calcium release (NICR) and synaptic plasticity in cerebellar Purkinje cells. Further studies on mutant animals deficient in redox-modification site may clarify essential role of redox signals in brain functions in vivo.