Neurosteroids in the Purkinje cell: Biosynthesis, mode of action and functional significance

Kazuyoshi Tsutsui

    Research output: Contribution to journalArticlepeer-review

    51 Citations (Scopus)

    Abstract

    Neurosteroids are synthesized de novo from cholesterol in the brain. To understand neurosteroid action in the brain, data on the regio- and temporal-specific synthesis of neurosteroids are needed. Recently the Purkinje cell, an important cerebellar neuron, has been identified as a major site for neurosteroid formation in 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 using the Purkinje cell as an excellent cellular model. In mammals, the Purkinje cell actively synthesizes progesterone and estradiol de novo from cholesterol during neonatal life. Both progesterone and estradiol promote dendritic growth, spinogenesis, and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such organizing actions that may be mediated by neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), contribute to the formation of cerebellar neuronal circuit during neonatal life. Allopregnanolone, a progesterone metabolite, is also synthesized in the cerebellum and acts on Purkinje cell survival in the neonate. This review summarizes the advances made in our understanding of the biosynthesis, mode of action and functional significance of neurosteroids in the Purkinje cell.

    Original languageEnglish
    Pages (from-to)116-125
    Number of pages10
    JournalMolecular Neurobiology
    Volume37
    Issue number2-3
    DOIs
    Publication statusPublished - 2008 Jun

    Keywords

    • Allopregnanolone
    • Brain-derived neurotrophic factor
    • Estradiol
    • Neuronal growth
    • Neurosteroids
    • Progesterone
    • Purkinje cell
    • Synaptogenesis

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience

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