Levetiracetam mitigates doxorubicin-induced DNA and synaptic damage in neurons
| Autor: | Yuri Dabaghian, Jose Felix Moruno Manchon, Shelli R. Kesler, Jeffrey S. Wefel, Ndidi Ese Uzor, Andrey S. Tsvetkov |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Programmed cell death Levetiracetam Neurite Cell Survival DNA damage Down-Regulation Pharmacology Biology Article 03 medical and health sciences Neurites medicine Animals DNA Breaks Double-Stranded Doxorubicin Cells Cultured Cell Nucleus Cerebral Cortex Neurons Multidisciplinary Cell Death BRCA1 Protein Neurotoxicity Piracetam medicine.disease Rats Neuroprotective Agents 030104 developmental biology medicine.anatomical_structure Cerebral cortex Synapses Tumor Suppressor p53-Binding Protein 1 DNA Damage medicine.drug |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep25705 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|