ArticleThe Journal of clinical investigation2009
Lithium-mediated protection of hippocampal cells involves enhancement of DNA-PK-dependent repair in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Lithium for Radiation-Induced Damage in Pediatric Brain Tumors: Preclinical Evidence and Clinical Perspectives.Journal of clinical medicine · 2026Review
- Lithium as a Potential Senostatic Agent in Central Nervous System Aging and Bipolar Disorder.Pharmaceuticals (Basel, Switzerland) · 2026Review
- GSK3B directs DNA repair choice and determines tumor response to PARP1 inhibition independent of BRCA1.The Journal of clinical investigation · 2025Article
- High Dosage Lithium Treatment Induces DNA Damage and p57International journal of molecular sciences · 2020Article
- GSK3β negatively regulates TRAX, a scaffold protein implicated in mental disorders, for NHEJ-mediated DNA repair in neurons.Molecular psychiatry · 2018Article
- The TRAX, DISC1, and GSK3 complex in mental disorders and therapeutic interventions.Journal of biomedical science · 2018Review
- MARCKS phosphorylation is modulated by a peptide mimetic of MARCKS effector domain leading to increased radiation sensitivity in lung cancer cell lines.Oncology letters · 2017Article
- miR-21-mediated Radioresistance Occurs via Promoting Repair of DNA Double Strand Breaks.The Journal of biological chemistry · 2017Article
- A novel role for the DNA repair gene Rad51 in Netrin-1 signalling.Scientific reports · 2017Article
- Lithium promotes DNA stability and survival of ischemic retinal neurocytes by upregulating DNA ligase IV.Cell death & disease · 2016Article
- Chronic Alcohol Exposure Decreases 53BP1 Protein Levels Leading to a Defective DNA Repair in Cultured Primary Cortical Neurons.Neurotoxicity research · 2016Article
- Lithium increases proliferation of hippocampal neural stem/progenitor cells and rescues irradiation-induced cell cycle arrest in vitro.Oncotarget · 2015Article
- Glycogen synthase kinase 3β orchestrates microtubule remodeling in compensatory glomerular adaptation to podocyte depletion.The Journal of biological chemistry · 2015Article
- WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.Acta neuropathologica communications · 2014Article
- Minocycline ameliorates cognitive impairment induced by whole-brain irradiation: an animal study.Radiation oncology (London, England) · 2014Article
- Glycogen synthase kinase 3β dictates podocyte motility and focal adhesion turnover by modulating paxillin activity: implications for the protective effect of low-dose lithium in podocytopathy.The American journal of pathology · 2014Article
- BRCA1-Ku80 protein interaction enhances end-joining fidelity of chromosomal double-strand breaks in the G1 phase of the cell cycle.The Journal of biological chemistry · 2013Article
- The role and clinical significance of DNA damage response and repair pathways in primary brain tumors.Cell & bioscience · 2013Article
- Endoglin (CD105) contributes to platinum resistance and is a target for tumor-specific therapy in epithelial ovarian cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Assaying DNA damage in hippocampal neurons using the comet assay.Journal of visualized experiments : JoVE · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Long-term neurological deficiencies resulting from hippocampal cytotoxicity induced by cranial irradiation (IR) present a challenge in the treatment of primary and metastatic brain cancers, especially in children. Previously, we showed that lithium protected hippocampal neurons from IR-induced apoptosis and improved neurocognitive function in treated mice. Here, we demonstrate accelerated repair of IR-induced chromosomal double-strand breaks (DSBs) in lithium-treated neurons. Lithium treatment not only increased IR-induced DNA-dependent protein kinase (DNA-PK) threonine 2609 foci, a surrogate marker for activated nonhomologous end-joining (NHEJ) repair, but also enhanced double-strand DNA end-rejoining activity in hippocampal neurons. The increased NHEJ repair coincided with reduced numbers of IR-induced gamma-H2AX foci, well-characterized in situ markers of DSBs. These findings were confirmed in vivo in irradiated mice. Consistent with a role of NHEJ repair in lithium-mediated neuroprotection, attenuation of IR-induced apoptosis of hippocampal neurons by lithium was dramatically abrogated when DNA-PK function was abolished genetically in SCID mice or inhibited biochemically by the DNA-PK inhibitor IC86621. Importantly, none of these findings were evident in glioma cancer cells. These results support our hypothesis that lithium protects hippocampal neurons by promoting the NHEJ repair-mediated DNA repair pathway and warrant future investigation of lithium-mediated neuroprotection during cranial IR, especially in the pediatric population.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.