| Literature DB >> 19162061 |
Marta Tajes1, Marc Yeste-Velasco, Xiongwei Zhu, Steven P Chou, Mark A Smith, Mercè Pallàs, Antoni Camins, Gemma Casadesús.
Abstract
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.Entities:
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Year: 2009 PMID： 19162061 DOI： 10.1016/j.mad.2008.12.006
Source DB: PubMed Journal: Mech Ageing Dev ISSN： 0047-6374 Impact factor: 5.432