Biosynthesis and organizing action of neurosteroids in the developing Purkinje cell

Kazuyoshi Tsutsui

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Probing undiscovered neurosubstances that play important roles in the regulation of cerebellar function is essential for the progress of our understanding of the cerebellum. New findings over the past decade have established that the cerebellum as well as other brain regions synthesizes steroids de novo from cholesterol through mechanisms at least partly independent of peripheral steroidogenic glands. Such steroids synthesized de novo in the brain are called neurosteroids. Recently the Purkinje cell, a cerebellar neuron, has been identified as a major site for neurosteroid formation in the brain. This is the first demonstration of de novo neuronal neurosteroidogenesis in the brain. In mammals, the Purkinje cell actively synthesizes progesterone de novo from cholesterol during neonatal life, when cerebellar cortical formation occurs. 3α,5α-Tetrahydroprogesterone (allopregnanolone) is metabolized from progesterone in the neonatal cerebellum. Estrogen formation in the Purkinje cell may also occur in the neonate. Subsequently, recent studies on mammals using the Purkinje cell have demonstrated organizing actions of neurosteroids. Both progesterone and estradiol promote dendritic growth, spinogenesis and synaptogenesis via each cognate nuclear receptor in Purkinje neurons. Allopregnanolone is also involved in Purkinje and granule cell survival. Thus the Purkinje cell serves as an excellent cellular model for understanding the formation of cerebellar neuronal circuit in relation to organizing actions of neurosteroids.

Original languageEnglish
Pages (from-to)89-96
Number of pages8
JournalCerebellum
Volume5
Issue number2
DOIs
Publication statusPublished - 2006 Jun 1
Externally publishedYes

Keywords

  • Cerebellar development
  • Neuronal growth
  • Neurosteroids
  • Purkinje cell
  • Synaptogenesis

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Biosynthesis and organizing action of neurosteroids in the developing Purkinje cell'. Together they form a unique fingerprint.

  • Cite this