Activation of Akt by lithium: Pro-survival pathways in aging
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- 作者：Marta Tajes ; Marc Yeste-Velasco ; Xiongwei Zhu ; Steven P. Chou ; Mark A. Smith ; Mercè ; Pallà ; s ; Antoni Camins ; Gemma Casadesú ; s
- 关键词：Neurodegeneration ; Lithium chloride ; SAMP8 ; Neuroprotection ; Aging
- 刊名：Mechanisms of Ageing and Development
- 出版年：2009
- 出版时间：April 2009
- 年：2009
- 卷：130
- 期：4
- 页码：253-261
- 全文大小：1248 K
文摘
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 (1–10 mM) exerts neuroprotective effects in young cultures (7–8 days) against LY294002-induced Akt inhibition. Furthermore, lithium (10 mM) inhibits GSK-3β activity by upregulating p-GSK-3β (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.