Cranial radiation therapy to treat brain cancer can result in various long-term neurological side effects, particularly in children. Lithium has protective properties in the brain that make it a potential therapy for reducing these side effects; however, little is known about the mechanisms by which it protects nerves. In a new study, Fen Xia and colleagues, at Vanderbilt University Medical Center, Nashville, present results, generated in irradiated mice, that lithium protects nerves in the region of the brain known as the hippocampus by promoting DNA repair. Specifically, a decreased number of double-strand DNA breaks were observed in lithium-treated, irradiated mice and brain cells compared to controls. This decrease was associated with increased markers for the nonhomologous end-joining DNA repair pathway. When this pathway was blocked in mice, lithium provided substantially less protection to the hippocampal nerve cells. The authors therefore conclude that lithium should be considered as a possible treatment to reduce the long-term neurological side effects of cranial radiation therapy, particularly in children, and that targeted therapies to enhance DNA repair may provide an avenue for future therapeutic development.
TITLE: Lithium-mediated protection of hippocampal cells involves enhancement of DNA-PK–dependent repair in mice
AUTHOR CONTACT:
Fen Xia
Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Phone: (615) 322-2555; Fax: (615) 343-0161; E-mail: fen.xia@vanderbilt.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=34051
Journal
Journal of Clinical Investigation