Possible role of pineal allopregnanolone in Purkinje cell survival

Shogo Haraguchi, Sakurako Hara, Takayoshi Ubuka, Masatoshi Mita, Kazuyoshi Tsutsui

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    Abstract

    It is believed that neurosteroids are produced in the brain and other nervous systems. Here, we show that allopregnanolone (ALLO), a neurosteroid, is exceedingly produced in the pineal gland compared with the brain and that pineal ALLO acts on the Purkinje cell, a principal cerebellar neuron, to prevent apoptosis in the juvenile quail. We first demonstrated that the pineal gland is a major organ of neurosteroidogenesis. A series of experiments using molecular and biochemical techniques has further demonstrated that the pineal gland produces a variety of neurosteroids de novo from cholesterol in the juvenile quail. Importantly, ALLO was far more actively produced in the pineal gland than in the brain. Pinealectomy (Px) decreased ALLO concentration in the cerebellum and induced apoptosis of Purkinje cells, whereas administration of ALLO to Px quail chicks prevented apoptosis of Purkinje cells.We further found that Px significantly increased the number of Purkinje cells that expressed active caspase-3, a key protease in apoptotic pathway, and daily injection of ALLO to Px quail chicks decreased the number of Purkinje cells expressing active caspase-3. These results indicate that the neuroprotective effect of pineal ALLO is associated with the decrease in caspase-3 activity during the early stage of neuronal development. We thus provide evidence that the pineal gland is an important neurosteroidogenic organ and that pineal ALLO may be involved in Purkinje cell survival during development. This is an important function of the pineal gland in the formation of neuronal circuits in the developing cerebellum.

    Original languageEnglish
    Pages (from-to)21110-21115
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume109
    Issue number51
    DOIs
    Publication statusPublished - 2012 Dec 18

    Fingerprint

    Pregnanolone
    Purkinje Cells
    Pineal Gland
    Cell Survival
    Quail
    Caspase 3
    Neurotransmitter Agents
    Apoptosis
    Cerebellum
    Brain
    Neuroprotective Agents
    Nervous System
    Peptide Hydrolases
    Cholesterol
    Neurons
    Injections

    Keywords

    • Gas chromatography/mass spectrometry
    • HPLC
    • Melatonin
    • Steroid

    ASJC Scopus subject areas

    • General

    Cite this

    Possible role of pineal allopregnanolone in Purkinje cell survival. / Haraguchi, Shogo; Hara, Sakurako; Ubuka, Takayoshi; Mita, Masatoshi; Tsutsui, Kazuyoshi.

    In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 51, 18.12.2012, p. 21110-21115.

    Research output: Contribution to journalArticle

    Haraguchi, Shogo ; Hara, Sakurako ; Ubuka, Takayoshi ; Mita, Masatoshi ; Tsutsui, Kazuyoshi. / Possible role of pineal allopregnanolone in Purkinje cell survival. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 51. pp. 21110-21115.
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