title: Levetiracetam mitigates doxorubicin-induced DNA and synaptic damage in neurons.
abstract: Neurotoxicity may occur in cancer patients and survivors during or after chemotherapy. Cognitive deficits associated with neurotoxicity can be subtle or disabling and frequently include disturbances in memory, attention, executive function and processing speed. Searching for pathways altered by anti-cancer treatments in cultured primary neurons, we discovered that doxorubicin, a commonly used anti-neoplastic drug, significantly decreased neuronal survival. The drug promoted the formation of DNA double-strand breaks in primary neurons and reduced synaptic and neurite density. Pretreatment of neurons with levetiracetam, an FDA-approved anti-epileptic drug, enhanced survival of chemotherapy drug-treated neurons, reduced doxorubicin-induced formation of DNA double-strand breaks, and mitigated synaptic and neurite loss. Thus, levetiracetam might be part of a valuable new approach for mitigating synaptic damage and, perhaps, for treating cognitive disturbances in cancer patients and survivors.
authors.affiliation: Department of Neurobiology and Anatomy, University of Texas, Houston Medical School, Houston, TX, USA.
authors.forename: Jose Felix Moruno
authors.initials: JF
authors.lastname: Manchon
authors.affiliation: The Jan and Dan Duncan Neurological Research Institute, Baylor College of Medicine, Houston, TX, USA.|Department of Computational and Applied Mathematics, Rice University, Houston, TX, USA.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Dabaghian
authors.affiliation: Department of Neurobiology and Anatomy, University of Texas, Houston Medical School, Houston, TX, USA.|The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA.
authors.forename: Ndidi-Ese
authors.initials: NE
authors.lastname: Uzor
authors.affiliation: Department of Neuro-Oncology, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Shelli R
authors.initials: SR
authors.lastname: Kesler
authors.affiliation: Department of Neuro-Oncology, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Wefel
authors.affiliation: Department of Neurobiology and Anatomy, University of Texas, Houston Medical School, Houston, TX, USA.|The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA.
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Tsvetkov
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects*; D000077287:Levetiracetam; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000071857:Tumor Suppressor p53-Binding Protein 1 / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; D018696:Neuroprotective Agents; D000071857:Tumor Suppressor p53-Binding Protein 1; D000077287:Levetiracetam; D004317:Doxorubicin; D010889:Piracetam