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Mech Ageing Dev. 2009 Apr;130(4):253-61. doi: 10.1016/j.mad.2008.12.006. Epub 2009 Jan 3.

Activation of Akt by lithium: pro-survival pathways in aging.

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Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina, Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain.


The effects of lithium on senescence were investigated using the senescence-accelerated mouse prone 8 (SAMP8) mice and cultures of aging cerebellar granule cells. Our in vitro findings, using cerebellar granule neurons, demonstrate that lithium (1-10mM) exerts neuroprotective effects in young cultures (7-8 days) against LY294002-induced Akt inhibition. Furthermore, lithium (10mM) inhibits GSK-3beta activity by upregulating p-GSK-3beta (ser-9) and increases p-FOXO1 (Ser256) suggesting an effective anti-apoptotic effect. Our data also showed that lithium in aged cultures exerts anti-apoptotic effects via Akt activation and consequent inhibition of downstream targets regulated by this enzyme. Finally, the administration of lithium to senescence-accelerated mice (SAMP8) and senescence-accelerated resistant mice (SAMR1) at 3 months of age also caused increased Akt activity and p-FoxO-1. These results demonstrate the effectiveness of lithium in preventing age-related neural loss and the potential therapeutic applications of lithium in treatment/prevention of neurological disease.

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