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Lithium and Valproate Protect Hippocampal Slices Against ATP-induced Cell Death

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Abstract

Lithium and valproate (VPA) are the most commonly prescribed mood-stabilizing drugs. Recently, several studies have reported their neuroprotective properties in several models of neural toxicity and, in some pathological conditions, large amounts of intracellular ATP can be released from damaged cells. In the present study, we investigate the potential neuroprotective effect of lithium and VPA against ATP-induced cell death in hippocampal slices of adult rats. Acute (in vitro) and chronic (in vivo) treatment at therapeutic doses with lithium or VPA significantly prevent the ATP-induced cell death. Lithium and VPA also exerted a synergic effect in the prevention of ATP-induced cell death. Moreover, hippocampal slices prepared from rats chronically treated with lithium or VPA presented a significant reduction in cell death in the presence of cytotoxic extracellular ATP. Although further investigations are necessary, our results show the neuroprotective effect of lithium and VPA against neuronal death induced by extracellular ATP, probably through a different pathway, and suggest novel uses of these drugs in neurogenerative diseases.

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Authors and Affiliations

  1. Departamento de Bioquímica—ICBS, Universidade Federal do Rio Grande do Sul, Av. Ramiro Barcelos, 2600 - anexo, Porto Alegre, RS, CEP 90035-003, Brazil

    Leandre Carmen Wilot, Andressa Bernardi, Rudimar Luiz Frozza, Ana Lucilia Marques, Helena Cimarosti, Christianne Salbego, Elizabete Rocha & Ana Maria Oliveira Battastini

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  1. Leandre Carmen Wilot
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  2. Andressa Bernardi
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  3. Rudimar Luiz Frozza
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  4. Ana Lucilia Marques
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  5. Helena Cimarosti
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  6. Christianne Salbego
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  7. Elizabete Rocha
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  8. Ana Maria Oliveira Battastini
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Correspondence to Ana Maria Oliveira Battastini.

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L. C. Wilot and A. Bernardi equally contributed by this work.

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Wilot, L.C., Bernardi, A., Frozza, R.L. et al. Lithium and Valproate Protect Hippocampal Slices Against ATP-induced Cell Death. Neurochem Res 32, 1539–1546 (2007). https://doi.org/10.1007/s11064-007-9348-3

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  • DOI: https://doi.org/10.1007/s11064-007-9348-3

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