Eugenia Yazlovitskaya
Faculty Member
Last active: 11/16/2017

Lithium treatment prevents neurocognitive deficit resulting from cranial irradiation.

Yazlovitskaya EM, Edwards E, Thotala D, Fu A, Osusky KL, Whetsell WO, Boone B, Shinohara ET, Hallahan DE
Cancer Res. 2006 66 (23): 11179-86

PMID: 17145862 · DOI:10.1158/0008-5472.CAN-06-2740

Curative cancer treatment regimens often require cranial irradiation, resulting in lifelong neurocognitive deficiency in cancer survivors. This deficiency is in part related to radiation-induced apoptosis and decreased neurogenesis in the subgranular zone of the hippocampus. We show that lithium treatment protects irradiated hippocampal neurons from apoptosis and improves cognitive performance of irradiated mice. The molecular mechanism of this effect is mediated through multiple pathways, including Akt/glycogen synthase kinase-3beta (GSK-3beta) and Bcl-2/Bax. Lithium treatment of the cultured mouse hippocampal neurons HT-22 induced activation of Akt (1.5-fold), inhibition of GSK-3beta (2.2-fold), and an increase in Bcl-2 protein expression (2-fold). These effects were sustained when cells were treated with lithium in combination with ionizing radiation. In addition, this combined treatment led to decreased expression (40%) of the apoptotic protein Bax. The additional genes regulated by lithium were identified by microarray, such as decorin and Birc1f. In summary, we propose lithium treatment as a novel therapy for prevention of deleterious neurocognitive consequences of cranial irradiation.

MeSH Terms (26)

Animals Apoptosis bcl-2-Associated X Protein Cell Line Cells, Cultured Cell Survival Cognition Disorders Cranial Irradiation Dose-Response Relationship, Radiation Female Gene Expression Glycogen Synthase Kinase 3 Glycogen Synthase Kinase 3 beta Hippocampus Lithium Chloride Male Mice Mice, Inbred C57BL Neurons Neuroprotective Agents Pregnancy Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins c-bcl-2 Rats Rats, Sprague-Dawley Signal Transduction

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