A molecular cell biology of lithium

Williams, Robin S. B.; Ryves, W. J.; Dalton, Emma; Eickholt, Britta J.; Shaltiel, Galit; Agam, Galila; Harwood, Adrian J.

doi:10.1042/bst0320799

Cited by 62 publications

(37 citation statements)

References 53 publications

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“…117 Mood stabilizers drugs could alter the morphogenesis of these new neurons and readjust interactions, which may either restore or augment neural activity. 118 If the processes modulating chemotaxis and neuronal morphology are fully investigated, it may eventually be possible to relate morphometric differences in brain structure between bipolar mood disorder patients and unaffected individuals 119 to changes in phosphatidylinositol signaling.…”

Section: Cytoskeletal Changesmentioning

confidence: 99%

Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited

2004

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Inositol, a simple six-carbon sugar, forms the basis of a number of important intracellular signaling molecules. Over the last 35 years, a series of biochemical and cell biological experiments have shown that lithium (Li þ ) reduces the cellular concentration of myo-inositol and as a consequence attenuates signaling within the cell. Based on these observations, inositol-depletion was proposed as a therapeutic mechanism in the treatment of bipolar mood disorder. Recent results have added significant new dimensions to the original hypothesis. However, despite a number of clinical studies, this hypothesis still remains to be either proven or refuted. In this review of our current knowledge, I will consider where the inositol-depletion hypothesis stands today and how it may be further investigated in the future.

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Section: Cytoskeletal Changesmentioning

confidence: 99%

Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited

2004

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“…For a more extensive discussion of the biochemical and physiological actions of lithium, the interested reader is directed to a number of reviews of such data (Jope, 1999;Phiel and Klein, 2001;Shaldubina et al, 2001;Chuang, 2004;Gould et al, 2004;Williams et al, 2004). This review begins with a discussion of baseline behaviors, and the effect of lithium upon them.…”

Section: The Continued Utility Of Animal Modelsmentioning

confidence: 99%

“…While the purpose of this review is not to fully detail possible mechanisms for the behaviors we have described, this is an obvious critical step in understanding the relevant biochemical actions of lithium. As detailed in Figure 1, lithium has a number of direct inhibitory actions on cellular enzymes, as well as indirect effects on cell signaling pathways and brain physiological processes (see (Jope, 1999;Phiel and Klein, 2001;Shaldubina et al, 2001;Chuang, 2004;Gould et al, 2004;Williams et al, 2004) for extensive discussions).…”

Section: Possible Mechanismsmentioning

confidence: 99%

The behavioral actions of lithium in rodent models: Leads to develop novel therapeutics

O’Donnell

Gould

2007

Neuroscience & Biobehavioral Reviews

121

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For nearly as long as lithium has been in clinical use for the treatment of bipolar disorder, depression, and other conditions, investigators have attempted to characterize its effects on behaviors in rodents. Lithium consistently decreases exploratory activity, rearing, aggression, and amphetamine-induced hyperlocomotion; and it increases the sensitivity to pilocarpine-induced seizures, decreases immobility time in the forced swim test, and attenuates reserpine-induced hypolocomotion. Lithium also predictably induces conditioned taste aversion and alterations in circadian rhythms. The modulation of stereotypy, sensitization, and reward behavior are less consistent actions of the drug. These behavioral models may be relevant to human symptoms and to clinical endophenotypes. It is likely that the actions of lithium in a subset of these animal models are related to the therapeutic efficacy, as well the side effects, of the drug. We conclude with a brief discussion of various molecular mechanisms by which these lithium-sensitive behaviors may be mediated, and comment on the ways in which rat and mouse models can be used more effectively in the future to address persistent questions about the therapeutically relevant molecular actions of lithium.

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“…However, a multiplicity of cell responses is elicited by lithium outside the nervous system and has profound effects on a variety of processes, including metabolism, cell proliferation and development (2,3). In particular, lithium is described as an inhibitor of the cell cycle (4)(5)(6)(7) and an accelerator of cell death (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Lithium induces mortality in medulloblastoma cell lines

et al. 2010

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Abstract. Lithium is the main therapeutic agent for the treatment of bipolar disorders but nerve cells are not the sole target of this drug. Indeed, lithium has been reported to target numerous cell types and to affect cell proliferation, differentiation and death. Lithium targets a variety of enzymes among which there is GSK-3ß and a number of cell responses elicited by lithium are mediated by the Wnt pathway that is involved in medulloblastoma (MB) pathogenesis. We studied the in vitro effects of lithium on two different MB cell lines: D283MED and DAOY. High doses of lithium inhibited GSK3-ß, decreased cell proliferation and induced nonapoptotic cell death in both cell lines independently by intracellular levels of ß-catenin that is consistently high only in D283MED. At clinical doses, the anti-neoplastic effects were observed only in this cell line, highlighting the importance of a specific molecular background in determining the target therapy response. In conclusion, lithium could be a promising drug in MB, but an accurate molecular profile predictive of drug response still needs to be clarified.

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A molecular cell biology of lithium

Cited by 62 publications

References 53 publications

Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited

Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited

The behavioral actions of lithium in rodent models: Leads to develop novel therapeutics

Lithium induces mortality in medulloblastoma cell lines

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