On the 50th anniversary of John Cade's discovery of the anti-manic effect of lithium*

Mitchell, Philip B.

doi:10.1046/j.1440-1614.1999.00607.x

Cited by 4 publications

(1 citation statement)

References 40 publications

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“…Both LiCl and BIO have potential for clinical application. LiCl has been used to treat psychiatric conditions such as bipolar disorder for many decades ( Mitchell, 1999 ) and BIO is part of the family of indirubins, which have been identified as the active ingredient of the Chinese medicine Danggui Longhui Wan, which has anti-leukemic activity ( Hoessel et al , 1999 ). Other GSK-3 inhibitors have been developed and tested in a variety of preclinical studies ( Meijer et al , 2004 ; Eldar-Finkelman and Martinez, 2011 ), however, current hurdles for the use of such drugs in clinical practice include optimisation of drug delivery and avoidance of toxic systemic accumulation of the drug.…”

Section: Discussionmentioning

confidence: 99%

Cell migration in paediatric glioma; characterisation and potential therapeutic targeting

et al. 2015

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Background:Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are highly aggressive brain tumours. Their invasive phenotype contributes to their limited therapeutic response, and novel treatments that block brain tumour invasion are needed.Methods:Here, we examine the migratory characteristics and treatment effect of small molecule glycogen synthase kinase-3 inhibitors, lithium chloride (LiCl) and the indirubin derivative 6-bromoindirubin-oxime (BIO), previously shown to inhibit the migration of adult glioma cells, on two pHGG cell lines (SF188 and KNS42) and one patient-derived DIPG line (HSJD-DIPG-007) using 2D (transwell membrane, immunofluorescence, live cell imaging) and 3D (migration on nanofibre plates and spheroid invasion in collagen) assays.Results:All lines were migratory, but there were differences in morphology and migration rates. Both LiCl and BIO reduced migration and instigated cytoskeletal rearrangement of stress fibres and focal adhesions when viewed by immunofluorescence. In the presence of drugs, loss of polarity and differences in cellular movement were observed by live cell imaging.Conclusions:Ours is the first study to demonstrate that it is possible to pharmacologically target migration of paediatric glioma in vitro using LiCl and BIO, and we conclude that these agents and their derivatives warrant further preclinical investigation as potential anti-migratory therapeutics for these devastating tumours.

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Section: Discussionmentioning

confidence: 99%

Cell migration in paediatric glioma; characterisation and potential therapeutic targeting

et al. 2015

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Targeting renal purinergic signalling for the treatment of lithium‐induced nephrogenic diabetes insipidus

et al. 2015

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Lithium still retains its critical position in the treatment of bipolar disorder by virtue of its ability to prevent suicidal tendencies. However, chronic use of lithium is often limited by the development nephrogenic diabetes insipidus (NDI), a debilitating condition. Lithium-induced NDI is due to resistance of the kidney to arginine vasopressin (AVP), leading to polyuria, natriuresis and kaliuresis. Purinergic signalling mediated by extracellular nucleotides (ATP/UTP), acting via P2Y receptors, opposes the action of AVP on renal collecting duct (CD) by decreasing the cellular cAMP and thus AQP2 protein levels. Taking a cue from this phenomenon, we discovered the potential involvement of ATP/UTP-activated P2Y2 receptor in lithium-induced NDI in rats, and showed that P2Y2 receptor knockout mice are significantly resistant to Li-induced polyuria, natriuresis and kaliuresis. Extension of these studies revealed that ADP-activated P2Y12 receptor is expressed in the kidney, and its irreversible blockade by the administration of clopidogrel bisulfate (Plavix®) ameliorates Li-induced NDI in rodents. Parallel in vitro studies showed that P2Y12 receptor blockade by the reversible antagonist PSB-0739 sensitizes CD to the action of AVP. Thus, our studies unraveled the potential beneficial effects of targeting P2Y2 or P2Y12 receptors to counter AVP resistance in lithium-induced NDI. If established in further studies, our findings may pave the way for the development of better and safer methods for the treatment of NDI by bringing a paradigm shift in the approach from the current therapies that predominantly counter the anti-AVP effects to those that enhance the sensitivity of the kidney to AVP action.

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Reflection.

2006

Aust N Z J Psychiatry

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On the 50th anniversary of John Cade's discovery of the anti-manic effect of lithium*

Cited by 4 publications

References 40 publications

Cell migration in paediatric glioma; characterisation and potential therapeutic targeting

Cell migration in paediatric glioma; characterisation and potential therapeutic targeting

Targeting renal purinergic signalling for the treatment of lithium‐induced nephrogenic diabetes insipidus

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