Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase-3 protein expression in the mouse suprachiasmatic nuclei

Eiko Iwahana, Masashi Akiyama, Kazuko Miyakawa, Ayumi Uchida, Jiro Kasahara, Kohji Fukunaga, Toshiyuki Hamada, Shigenobu Shibata

    Research output: Contribution to journalArticle

    83 Citations (Scopus)

    Abstract

    A circadian clock located in the suprachiasmatic nucleus (SCN) regulates the period of physiological and behavioural rhythms to approximately 24 h. Lithium can lengthen the period of circadian rhythms in most organisms although little is known about the underlying mechanism. In the present study, we examined Drosophila shaggy ortholog glycogen synthase kinase-3 (GSK-3) protein expression in the SCN after lithium treatment. When locomotor activity was assessed, we found an association between the effect of lithium and the period of circadian oscillation as well as the level of GSK-3 protein expression. The decreased expression of GSK-3 and increased expression of phosphorylated GSK-3 (pGSK-3) resulted in an antiphasic circadian rhythm between the two in the SCN of lithium-treated mice housed under both light-dark and constant dark conditions. The enzyme activity of GSK-3 in the SCN was low when the level of pGSK-3 protein was high, as examined by immunoblotting analysis. Thus, GSK-3 enzyme activity has a correlation with the expression of GSK-3 protein in the SCN. Although both GSK-3 and pGSK-3 proteins are also expressed in the arcuate nucleus, lithium did not affect their expression. Based on the association that we found between lengthened circadian period and GSK-3 protein and GSK-3 activity in the SCN, we suggest that GSK-3 plays a role in regulating the period of the mammalian circadian pacemaker.

    Original languageEnglish
    Pages (from-to)2281-2287
    Number of pages7
    JournalEuropean Journal of Neuroscience
    Volume19
    Issue number8
    DOIs
    Publication statusPublished - 2004 Apr

    Fingerprint

    Glycogen Synthase Kinase 3
    Suprachiasmatic Nucleus
    Locomotion
    Circadian Rhythm
    Lithium
    Proteins
    Arcuate Nucleus of Hypothalamus
    Circadian Clocks
    Enzymes
    Immunoblotting
    Drosophila

    Keywords

    • Circadian rhythm
    • Glycogen synthase kinase-3
    • Lithium
    • Suprachiasmatic nucleus

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase-3 protein expression in the mouse suprachiasmatic nuclei. / Iwahana, Eiko; Akiyama, Masashi; Miyakawa, Kazuko; Uchida, Ayumi; Kasahara, Jiro; Fukunaga, Kohji; Hamada, Toshiyuki; Shibata, Shigenobu.

    In: European Journal of Neuroscience, Vol. 19, No. 8, 04.2004, p. 2281-2287.

    Research output: Contribution to journalArticle

    Iwahana, Eiko ; Akiyama, Masashi ; Miyakawa, Kazuko ; Uchida, Ayumi ; Kasahara, Jiro ; Fukunaga, Kohji ; Hamada, Toshiyuki ; Shibata, Shigenobu. / Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase-3 protein expression in the mouse suprachiasmatic nuclei. In: European Journal of Neuroscience. 2004 ; Vol. 19, No. 8. pp. 2281-2287.
    @article{4a6db3625e824bbbb9949d1417acadf5,
    title = "Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase-3 protein expression in the mouse suprachiasmatic nuclei",
    abstract = "A circadian clock located in the suprachiasmatic nucleus (SCN) regulates the period of physiological and behavioural rhythms to approximately 24 h. Lithium can lengthen the period of circadian rhythms in most organisms although little is known about the underlying mechanism. In the present study, we examined Drosophila shaggy ortholog glycogen synthase kinase-3 (GSK-3) protein expression in the SCN after lithium treatment. When locomotor activity was assessed, we found an association between the effect of lithium and the period of circadian oscillation as well as the level of GSK-3 protein expression. The decreased expression of GSK-3 and increased expression of phosphorylated GSK-3 (pGSK-3) resulted in an antiphasic circadian rhythm between the two in the SCN of lithium-treated mice housed under both light-dark and constant dark conditions. The enzyme activity of GSK-3 in the SCN was low when the level of pGSK-3 protein was high, as examined by immunoblotting analysis. Thus, GSK-3 enzyme activity has a correlation with the expression of GSK-3 protein in the SCN. Although both GSK-3 and pGSK-3 proteins are also expressed in the arcuate nucleus, lithium did not affect their expression. Based on the association that we found between lengthened circadian period and GSK-3 protein and GSK-3 activity in the SCN, we suggest that GSK-3 plays a role in regulating the period of the mammalian circadian pacemaker.",
    keywords = "Circadian rhythm, Glycogen synthase kinase-3, Lithium, Suprachiasmatic nucleus",
    author = "Eiko Iwahana and Masashi Akiyama and Kazuko Miyakawa and Ayumi Uchida and Jiro Kasahara and Kohji Fukunaga and Toshiyuki Hamada and Shigenobu Shibata",
    year = "2004",
    month = "4",
    doi = "10.1111/j.0953-816X.2004.03322.x",
    language = "English",
    volume = "19",
    pages = "2281--2287",
    journal = "European Journal of Neuroscience",
    issn = "0953-816X",
    publisher = "Wiley-Blackwell",
    number = "8",

    }

    TY - JOUR

    T1 - Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase-3 protein expression in the mouse suprachiasmatic nuclei

    AU - Iwahana, Eiko

    AU - Akiyama, Masashi

    AU - Miyakawa, Kazuko

    AU - Uchida, Ayumi

    AU - Kasahara, Jiro

    AU - Fukunaga, Kohji

    AU - Hamada, Toshiyuki

    AU - Shibata, Shigenobu

    PY - 2004/4

    Y1 - 2004/4

    N2 - A circadian clock located in the suprachiasmatic nucleus (SCN) regulates the period of physiological and behavioural rhythms to approximately 24 h. Lithium can lengthen the period of circadian rhythms in most organisms although little is known about the underlying mechanism. In the present study, we examined Drosophila shaggy ortholog glycogen synthase kinase-3 (GSK-3) protein expression in the SCN after lithium treatment. When locomotor activity was assessed, we found an association between the effect of lithium and the period of circadian oscillation as well as the level of GSK-3 protein expression. The decreased expression of GSK-3 and increased expression of phosphorylated GSK-3 (pGSK-3) resulted in an antiphasic circadian rhythm between the two in the SCN of lithium-treated mice housed under both light-dark and constant dark conditions. The enzyme activity of GSK-3 in the SCN was low when the level of pGSK-3 protein was high, as examined by immunoblotting analysis. Thus, GSK-3 enzyme activity has a correlation with the expression of GSK-3 protein in the SCN. Although both GSK-3 and pGSK-3 proteins are also expressed in the arcuate nucleus, lithium did not affect their expression. Based on the association that we found between lengthened circadian period and GSK-3 protein and GSK-3 activity in the SCN, we suggest that GSK-3 plays a role in regulating the period of the mammalian circadian pacemaker.

    AB - A circadian clock located in the suprachiasmatic nucleus (SCN) regulates the period of physiological and behavioural rhythms to approximately 24 h. Lithium can lengthen the period of circadian rhythms in most organisms although little is known about the underlying mechanism. In the present study, we examined Drosophila shaggy ortholog glycogen synthase kinase-3 (GSK-3) protein expression in the SCN after lithium treatment. When locomotor activity was assessed, we found an association between the effect of lithium and the period of circadian oscillation as well as the level of GSK-3 protein expression. The decreased expression of GSK-3 and increased expression of phosphorylated GSK-3 (pGSK-3) resulted in an antiphasic circadian rhythm between the two in the SCN of lithium-treated mice housed under both light-dark and constant dark conditions. The enzyme activity of GSK-3 in the SCN was low when the level of pGSK-3 protein was high, as examined by immunoblotting analysis. Thus, GSK-3 enzyme activity has a correlation with the expression of GSK-3 protein in the SCN. Although both GSK-3 and pGSK-3 proteins are also expressed in the arcuate nucleus, lithium did not affect their expression. Based on the association that we found between lengthened circadian period and GSK-3 protein and GSK-3 activity in the SCN, we suggest that GSK-3 plays a role in regulating the period of the mammalian circadian pacemaker.

    KW - Circadian rhythm

    KW - Glycogen synthase kinase-3

    KW - Lithium

    KW - Suprachiasmatic nucleus

    UR - http://www.scopus.com/inward/record.url?scp=2342477767&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=2342477767&partnerID=8YFLogxK

    U2 - 10.1111/j.0953-816X.2004.03322.x

    DO - 10.1111/j.0953-816X.2004.03322.x

    M3 - Article

    VL - 19

    SP - 2281

    EP - 2287

    JO - European Journal of Neuroscience

    JF - European Journal of Neuroscience

    SN - 0953-816X

    IS - 8

    ER -