title: Possible role of pineal allopregnanolone in Purkinje cell survival.
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.
authors.affiliation: Laboratory of Integrative Brain Sciences, Department of Biology and Center for Medical Life Science,  Waseda University, Tokyo 162-8480,  Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Haraguchi
authors.forename: Sakurako
authors.initials: S
authors.lastname: Hara
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ubuka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Mita
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Tsutsui
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000096:biosynthesis; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D008550:Melatonin / Q000378:metabolism; D010870:Pineal Gland / Q000166:cytology* / Q000601:surgery; D011280:Pregnanolone / Q000494:pharmacology*; D011689:Purkinje Cells / Q000378:metabolism*; D011784:Quail; D013256:Steroids / Q000737:chemistry / Q000378:metabolism
chemical_list: D013256:Steroids; D011280:Pregnanolone; D053148:Caspase 3; D008550:Melatonin