Melatonin protects against methotrexate-induced memory deficit and hippocampal neurogenesis impairment in a rat model

Biochemical Pharmacology
Apiwat SirichoatJariya Umka Welbat

Abstract

Methotrexate (MTX) is a chemotherapy agent linked to cognitive deficits in cancer patients received chemotherapy treatment. MTX decreases cell proliferation in the hippocampus, which is concomitant with cognitive deficits in animal models. The present study aimed to investigate the disadvantages of MTX on cognition associated with cell division, survival, and immature neurons involved in hippocampal neurogenesis, as well as the practical neuroprotective effects of melatonin. Male Sprague Dawley rats were given two injections of MTX (75 mg/kg) on days 8 and 15 followed by Leucovorin (LCV, 6 mg/kg) at hours 18, 26, 42, 50 via i.p. injection. Some rats received co-treatment with melatonin (8 mg/kg, i.p. injection) for 15 days before and during MTX administration (preventive), 15 days after MTX administration (recovery), or both (30 days total; throughout). Hippocampal-dependent memory was examined using novel objection location (NOL) and novel object recognition (NOR) tests. Cell division, survival and immature neurons in the subgranular zone (SGZ) in the hippocampus were evaluated using immunofluorescence staining. Rats given MTX/LCV were found to have cognitive memory deterioration based on the NOL and NOR tests. Moreover, reduc...Continue Reading

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Citations

Aug 13, 2020·International Journal of Molecular Sciences·Joseph Wai-Hin LeungBenson Wui-Man Lau
Jan 23, 2021·Expert Opinion on Drug Safety·Mariella Spalato, Antoine Italiano
Jul 3, 2021·International Journal of Molecular Sciences·Yu-Chieh ChenLi-Tung Huang
Nov 26, 2021·Food & Function·Abudumijiti AbuliziBaoxue Yang

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