Kainate-induced toxicity in the hippocampus: potential role of lithium

Bipolar Disorders
Natalia Crespo-BielMercè Pallàs

Abstract

We investigated the neuroprotective effects of lithium in an experimental neurodegeneration model gated to kainate (KA) receptor activation. The hippocampus from KA-treated mice and hippocampal cell cultures were used to evaluate the pathways regulated by chronic lithium pretreatment in both in vivo and in vitro models. Treatment with KA, as measured by fragmentation of alpha-spectrin and biochemically, induced the activation of calpain resulting in p35 cleavage to p25, indicating activation of cyclin-dependent kinase 5 (cdk5) and glycogen synthase kinase-3ss (GSK-3ss) and an increase in tau protein phosphorylation. Treatment with lithium reduced calpain activation and reduced the effects of cdk5 and GSK-3ss on tau. KA treatment of cultures resulted in neuronal demise. According to nuclear condensed cell counts, the addition of lithium to neuronal cell cultures (0.5-1 mM) a few days before KA treatment had neuroprotective and also antiapoptotic effects. The action of lithium on calpain/cdk5 and GSK-3ss pathways produced similar results in vivo. As calpain is activated by an increase in intracellular calcium, we showed that lithium reduced calcium concentrations in basal and KA-treated hippocampal cells, which was accompanied by...Continue Reading

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Citations

Jul 14, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Olena Y GlushakovaStefania Mondello
Mar 18, 2015·Brain Research·Jerónimo Jurado-ArjonaFélix Hernández
Sep 6, 2013·Pharmaceutical Biology·Zahra KiasalariTourandokht Baluchnejadmojarad
Oct 22, 2014·Proceedings of the National Academy of Sciences of the United States of America·Hei-Man ChowJie Zhang

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