It was already shown that microdoses of lithium carbonate (Li2CO3) promoted memory stabilization in humans and mice. Prolonged treatment also reduced neuronal loss and increased the density of the neurotrophin BDNF in transgenic mice for Alzheimer's disease. The aim of this study was to evaluate whether lithium ions affect inflammatory profiles and neuronal integrity in an animal model of accelerated senescence (SAMP-8).Organotypic hippocampal cultures obtained from 11 to 12-month-old SAMP-8 mice were treated with 2µM, 20µM and 200µM Li2CO3. 2µM Li2CO3 promoted a significant reduction in propidium iodide uptake in the CA2 area of hippocampus, whereas 20µM promoted neuroprotection in the CA3 and GrDG areas. 200µM caused an increase in cellular death, showing toxicity. Measured with quantitative PCR, IL-1α, IL-6 and MIP-1B/CCL-4 gene expression was significantly reduced with 20µM Li2CO3, whereas IL-10 gene expression was significantly increased with the same concentration. In addition, 2µM and 20µM Li2CO3 were also effective in reducing the activation of NFkB and inflammatory cytokines densities, as evaluated by ELISA. It is concluded that very low doses of Li2CO3 can play an important role in neuroprotection as it can reduce neuronal loss and neuroinflammation in older individuals.