A Slowing Down of Circadian Rhythms by Lithium Ions

Engelmann, Wolfgang

doi:10.1515/znc-1973-11-1214

Cited by 96 publications

(28 citation statements)

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“…The free-running period length of the circadian rhythm increases slightly in mice given a daily dose of LiCl in water (44). If the target of LiCl was GSK-3␤ in that study, then our data are consistent with their findings because the effects of lithium might be explained as action on GSK-3␤ that regulates the circadian clock.…”

Section: Figsupporting

confidence: 90%

A Role for Glycogen Synthase Kinase-3β in the Mammalian Circadian Clock

Iitaka

Miyazaki

Akaike

et al. 2005

Journal of Biological Chemistry

339

319

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The Drosophila shaggy gene product is a mammalian glycogen synthase kinase-3␤ (GSK-3␤) homologue that contributes to the circadian clock of the Drosophila through TIMELESS phosphorylation, and it regulates nuclear translocation of the PERIOD/TIMELESS heterodimer. We found that mammalian GSK-3␤ is expressed in the suprachiasmatic nucleus and liver of mice and that GSK-3␤ phosphorylation exhibits robust circadian oscillation. Rhythmic GSK-3␤ phosphorylation is also observed in serum-shocked NIH3T3 cells. Exposing serum-shocked NIH3T3 cells to lithium chloride, a specific inhibitor of GSK-3␤, increases GSK-3␤ phosphorylation and delays the phase of rhythmic clock gene expression. On the other hand, GSK-3␤ overexpression advances the phase of clock gene expression. We also found that GSK-3␤ interacts with PERIOD2 (PER2) in vitro and in vivo. Recombinant GSK-3␤ can phosphorylate PER2 in vitro. GSK-3␤ promotes the nuclear translocation of PER2 in COS1 cells. The present data suggest that GSK-3␤ plays important roles in mammalian circadian clock.

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Section: Figsupporting

confidence: 90%

A Role for Glycogen Synthase Kinase-3β in the Mammalian Circadian Clock

Iitaka

Miyazaki

Akaike

et al. 2005

Journal of Biological Chemistry

339

319

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“…Behavioral data suggest that both deuterium oxide, i.e., 'heavy water' [Daan and Pittendrigh, 1976], and chronic lithium [Engelmann, 1973;Kripke et al, 1978Kripke et al, . 1980Strumwasser and Vielle, 1980;Johnsson et al, 1980;Katz, 1980] slow circadian pace makers.…”

Section: Discussionmentioning

confidence: 99%

“…1980). Lithium has been shown to delay the phase-positions of some behavioral circadian rhythms such as sleeping and waking in man [Engelmann, 1973;Johnsson el al., 1979Johnsson el al., , 1980, and the rest-activity cycle in the rat [Kripke and Wyborney, 1980] and to slow the rate of a circadian pacemaker cell in Aplysia [Strumwasser and Vielle, 1980]. Previous studies have documented that circadian rhythms in the number of rat brain a-and P-adrenergic [Kafka et al, 1981a], acetylcho line [Kafka et al, 1981b], dopaminergic [Naberct al.. 1980], and benzodiazepine [Marangos et al, in preparation] receptors are signif icantly modified by chronic administration of two drugs, which like lithium are antide pressant, viz., imipramine [Naber et al, 1980;Wirz-Justice et al, 1980a, b: Kafka et al.…”

Section: Introductionmentioning

confidence: 99%

Effect of Lithium on Circadian Neurotransmitter Receptor Rhythms

Kafka

Wirz‐Justice²,

Naber

et al. 1982

Neuropsychobiology

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Chronic lithium administration significantly changes characteristics of the circadian rhythms in rat brain α- and β-adrenergic, muscarinic acetylcholine, dopamine, opiate, and benzodiazepine receptors. There are changes in the timing of the peak number of receptors (phase-position), in the amplitude of the rhythms, and in the 24-hour mean number of receptors. The circadian rhythm in the number of forebrain α- and β-adrenergic and benzodiazepine receptors is abolished. The phase-position of forebrain acetylcholine and opiate receptors and striatal benzodiazepine receptors is delayed. As the rhythms of the dopamine receptor number and α-melanocyte-stimulating hormone secretion become bimodal, their phase positions are difficult to evaluate. The mean number of forebrain α- and β-adrenergic, acetylcholine, opiate, and striatal benzodiazepine receptors increases. The mean number of forebrain benzodiazepine and striatal dopamine receptors and the mean concentration of α-melanocyte-stimulating hormone decreases. Lithium has profound effects on each of the receptor rhythms measured. Slowing and altering circadian rhythms may contribute to the therapeutic effects of chronic lithium treatment in affective disorders.

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“…Its period-lengthening effect on circadian rhythms has been documented in a great variety of species, e.g., desert cactus (8), cockroaches (15), molluscs (42}, hamsters (4,15), desert rats (8), rats (24,41), mice (33), squirrel monkeys (46), and humans (16). to the effect that the therapeutic effect of these drugs may be based on their phase delaying effect on the circadian pacemaker.…”

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confidence: 99%

Effect of lithium carbonate on activity level and circadian period in different strains of rats

Hafen

Wollnik

1994

Pharmacology Biochemistry and Behavior

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HAFEN, T. AND F. WOLLNIK. Effect of lithium carbonate on activity level and circadian period in different strains of rats. PHARMACOL BIOCHEM BEHAV 49(4) [975][976][977][978][979][980][981][982][983] 1994.-Lithium, an important pharmacological agent for the treatment of manic-depressive illness in humans, is known to lengthen the circadian period in a number of different species. Recent experiments, on the other hand, suggest that pharmacological agents may affect the circadian system indirectly through an increase or decrease of activity. To explore the interaction between pharmacological and activity effects on the circadian system, lithium was administered chronically to three different strains of rats (ACI, BH, and LEW) while wheel-running activity was studied quantitatively. Two of these inbred strains (BH and LEW) show profound abnormalities in their circadian activity rhythms, namely, a reduced overall level of activity and bimodal or multimodal activity patterns. Wheel-running activity was monitored for 4 weeks under baseline conditions, followed by 3 weeks with lithium treatment (0.3% Li 2 C0 1 administered with food) and 4 weeks with normal food. Treatment with lithium (average intake per day = 3.6 ± 0.2 mg) consistently decreased both the overall level and the circadian amplitude of the activity rhythm. The free-running period r was slightly lengthened during lithium treatment, while the most dramatic effect on period was observed after lithium withdrawal. Correlation analysis, however, revealed only a small negative correlation between activity level and period length, which proved significant only for animals of the ACI strain. Our data support the traditional interpretation that lithium lengthens circadian period by a direct pharmacological effect on the circadian pacemaker rather than through indirect effects of activity feedback. to the effect that the therapeutic effect of these drugs may be based on their phase delaying effect on the circadian pacemaker. So far, the mechanisms responsible for lithium's chronopharmacological actions are not known. It has been suggested that lithium could lengthen the circadian period by a) slowing of cellular oscillators, b) by altering the coupling between multiple circadian oscillators, or c) by altering light sensitivity (17). The hypothesis that lithium may weaken the mutual interaction between multiple oscillators is especially intriguing because modifications in coupling strength could theoretically account for changes in period, as well as entrained phase, wave form, and amplitude of circadian rhythms. Circadian rhythmsThe period-lengthening effect of lithium is of special interest with respect to the hypothesis that there may be an association between the pathophysiology of affective disorders and disturbances of circadian rhythms (22,48). Several studies in humans have demonstrated that many circadian rhythms are phase advanced in depressed patients compared to controls [reviewed in (12,44,45)]. Because lithium and a few other antidepressant agents (5,47...

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A Slowing Down of Circadian Rhythms by Lithium Ions

Cited by 96 publications

References 0 publications

A Role for Glycogen Synthase Kinase-3β in the Mammalian Circadian Clock

A Role for Glycogen Synthase Kinase-3β in the Mammalian Circadian Clock

Effect of Lithium on Circadian Neurotransmitter Receptor Rhythms

Effect of lithium carbonate on activity level and circadian period in different strains of rats

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