Lithium may protect the brain from damage from Radiation therapy for brain mets

[Lani]

Journal of Clinical Investigation
Lithium protects brain cells during cranial radiation

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.

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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

[Lani]

and found this:
for those requiring whole brain irradiation--lithium protects cognitive function
in mice so far, but anything that may preserve cognitive function should be considered


Lithium Treatment Prevents Neurocognitive Deficit Resulting from Cranial Irradiation

Eugenia M. Yazlovitskaya1,2, Eric Edwards1, Dinesh Thotala1, Allie Fu1, Kate L. Osusky1, William O. Whetsell, Jr.3, Braden Boone4, Eric T. Shinohara1 and Dennis E. Hallahan1,2
1 Department of Radiation Oncology, 2 Vanderbilt-Ingram Cancer Center, 3 Department of Pathology, and 4 Vanderbilt Microarray Shared Resource, Vanderbilt University School of Medicine, Nashville, Tennessee

Requests for reprints: Dennis E. Hallahan, Department of Radiation Oncology, Vanderbilt University, 1301 22nd Avenue South, B-902 The Vanderbilt Clinic, Nashville, TN 37232-5671. Phone: 615-343-9244; Fax: 615-343-3075; E-mail: Dennis.Hallahan@vanderbilt.edu.


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-3ß (GSK-3ß) and Bcl-2/Bax. Lithium treatment of the cultured mouse hippocampal neurons HT-22 induced activation of Akt (1.5-fold), inhibition of GSK-3ß (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. (Cancer Res 2006; 66(23): 11179-86)