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Impacts of methotrexate on survival, dendrite development, and synapse formation of cortical neurons.
Yamamura, Mai; Hanamura, Kenji; Koganezawa, Noriko; Furubayashi, Senami; Shirao, Tomoaki; Kawabe, Hiroshi.
Affiliation
  • Yamamura M; Department of Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
  • Hanamura K; Department of Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
  • Koganezawa N; Department of Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
  • Furubayashi S; Gunma University School of Medicine, Maebashi, Gunma, Japan.
  • Shirao T; Department of Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
  • Kawabe H; Department of Pharmacology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Genes Cells ; 28(8): 563-572, 2023 Aug.
Article in En | MEDLINE | ID: mdl-37170756
Methotrexate (MTX) is an anti-metabolite that has been used for the treatment of patients of acute lymphocytic leukemia or non-Hodgikin lymphoma for decades. In some cases, MTX-treated patients suffer from neurological side effects, including seizures and cognitive dysfunctions. While most patients are at developmental stages, information of the mechanisms of the side effects of MTX treatment on the developing neurons has been limited. Neurons develop in five steps in the human brain: neurogenesis, polarity formation, dendrite and axon development, synapse formation, and neuronal death. Except for neurogenesis, these processes can be recapitulated in the primary culture system of cortical neurons. Using primary cultured cortical neurons, we studied the impact of MTX treatment on dendrite development, synapse formation, and neuronal death in the present report. MTX treatment impaired neuronal survival, dendrite development, and synapse formation. Interestingly, half maximal effective concentrations (EC50 s) of MTX for all three processes are at the similar range and lower than the MTX concentration in the cerebrospinal fluid in treated patients. Our results provide possible mechanisms of neurological side effects in treated patients.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Methotrexate / Neurons Limits: Humans Language: En Journal: Genes Cells Journal subject: BIOLOGIA MOLECULAR Year: 2023 Document type: Article Affiliation country: Japón Country of publication: Reino Unido

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Methotrexate / Neurons Limits: Humans Language: En Journal: Genes Cells Journal subject: BIOLOGIA MOLECULAR Year: 2023 Document type: Article Affiliation country: Japón Country of publication: Reino Unido