Biosynthesis, mode of action and functional significance of neurosteroids in the developing Purkinje cell

Abstract

New findings over the past decade have shown that the brain has the capability of forming steroids de novo from cholesterol, the so-called “neurosteroids”. To understand neurosteroid action in the brain, data on the regio- and temporal-specific synthesis of neurosteroids are needed. Recently, we have demonstrated that the Purkinje cell, a cerebellar neuron, is a major site for neurosteroid formation in a variety of vertebrates. This is the first demonstration of de novo neuronal neurosteroidogenesis in the brain. Since this discovery, organizing actions of neurosteroids are becoming clear by the studies on mammals using the Purkinje cell as an excellent cellular model. In mammals, the Purkinje cell actively synthesizes progesterone de novo from cholesterol during neonatal life, when cerebellar neuronal circuit formation occurs. The Purkinje cell may also produces estradiol in the neonate. Interestingly, both progesterone and estradiol promote dendritic growth, spinogenesis and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such organizing actions may contribute to the formation of cerebellar neuronal circuit during neonatal life. This paper summarizes the advances made in our understanding of the biosynthesis, mode of action and functional significance of neurosteroids in the developing Purkinje cell.