Effect of Methotrexate on Recognition Memory in Adult Female Mice
DOI:
https://doi.org/10.54172/mjsc.v37i2.617Keywords:
cognitive impairment, Intraperitonly, Methotrexate, Novel recognition task, Recognition memoryAbstract
Methotrexate MTX is used to treat some types of cancers, skin diseases, and rheumatic diseases. Many studies have suggested that it may lead to memory damage in mice. Accordingly, this study was conducted to investigate the effect of different doses of methotrexate on recognition memory in mice. Twenty-four adult female albino mice (weighing between 30-36 g) were divided equally into four groups and subjected to one of the following treatments: the control group (injected with normal saline), the second group treated with a dose of 20 mg/kg of MTX, the third group treated with a dose of 40 mg/kg of MTX, the fourth group treated with a dose of 80 mg/kg of MTX. All doses were given once intraperitoneally. A memory test was performed half an hour after injection, comprising object training and a new object recognition test. The results of this study showed that the MTX-injected mice had a lower rate of exploration of the novel object compared to the control group, and MTX has a dose-dependent negative effect on cognitive behavior. These findings suggest that methotrexate has a negative effect on the recognition memory of mice.
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Akman, A. U. (2021). Methotrexate Induced Hepatotoxicity and Antioxidants. Sabuncuoglu Serefeddin Health Sciences, 3(1), 22-35.
Aldosouky, E., Elfagieh, M., & Jebriel, A. (2011). Pediatric Burkitt’s lymphoma (diagnosis and treatment evaluation) in NCI, Pediatric Oncology Unit: Misurata/Libya initial experience. Journal of Clinical Oncology, 29(15_suppl), e20000-e20000.
Aukema, E. J., Caan, M. W., Oudhuis, N., Majoie, C. B., Vos, F. M., Reneman, L., Last, B. F., Grootenhuis, M. A., & Schouten-van Meeteren, A. Y. (2009). White matter fractional anisotropy correlates with speed of processing and motor speed in young childhood cancer survivors. International Journal of Radiation Oncology* Biology* Physics, 74(3), 837-843.
Bedoui, Y., Guillot, X., Sélambarom, J., Guiraud, P., Giry, C., Jaffar-Bandjee, M. C., Ralandison, S., & Gasque, P. (2019). Methotrexate an old drug with new tricks. International journal of molecular sciences, 20(20), 5023.
Bisen-Hersh, E. B., Hineline, P. N., & Walker, E. A. (2013). Effects of early chemotherapeutic treatment on learning in adolescent mice: implications for cognitive impairment and remediation in childhood cancer survivors. Clinical Cancer Research, 19(11), 3008-3018.
Broadbent, N. J., Gaskin, S., Squire, L. R., & Clark, R. E. (2010). Object recognition memory and the rodent hippocampus. Learning & memory, 17(1), 5-11.
Cohen, S. J., & Stackman Jr, R. W. (2015). Assessing rodent hippocampal involvement in the novel object recognition task. A review. Behavioural brain research, 285, 105-117.
Dukic, S., Heurtaux, T., Kaltenbach, M., Hoizey, G., Lallemand, A., & Vistelle, R. (2000). Influence of schedule of administration on methotrexate penetration in brain tumours. European Journal of Cancer, 36(12), 1578-1584.
Elens, I., Dekeyster, E., Moons, L., & D'Hooge, R. (2019). Methotrexate affects cerebrospinal fluid folate and tau levels and induces late cognitive deficits in mice. Neuroscience, 404, 62-70.
Ermens, A. A., Schoester, M., Spijkers, L. J., Lindemans, J., & Abels, J. (1989). Toxicity of methotrexate in rats preexposed to nitrous oxide. Cancer research, 49(22), 6337-6341.
Etaher, N. A., Saeed, N. M., Elmejrab, M. M., Sherif, R. F., & Sherif, F. M. (2021). Prescribing Patterns of Methotrexate in Libyan Patients with Rheumatoid Arthritis. City, 29, 24.
Inagaki, M., Yoshikawa, E., Matsuoka, Y., Sugawara, Y., Nakano, T., Akechi, T., Wada, N., Imoto, S., Murakami, K., & Uchitomi, Y. (2007). Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy. Cancer, 109(1), 146-156.
John, J., Kinra, M., Mudgal, J., Viswanatha, G., & Nandakumar, K. (2021). Animal models of chemotherapy-induced cognitive decline in preclinical drug development. Psychopharmacology, 238(11), 3025-3053.
Kempermann, G. (2002). Why new neurons? Possible functions for adult hippocampal neurogenesis. Journal of neuroscience, 22(3), 635-638.
Li, Y., Vijayanathan, V., Gulinello, M. E., & Cole, P. D. (2010). Systemic methotrexate induces spatial memory deficits and depletes cerebrospinal fluid folate in rats. Pharmacology Biochemistry and Behavior, 94(3), 454-463.
Lyons, L., ElBeltagy, M., Umka, J., Markwick, R., Startin, C., Bennett, G., & Wigmore, P. (2011). Fluoxetine reverses the memory impairment and reduction in proliferation and survival of hippocampal cells caused by methotrexate chemotherapy. Psychopharmacology, 215(1), 105-115.
Madhyastha, S., Somayaji, S., Rao, M., Nalini, K., & Bairy, K. L. (2002). Hippocampal brain amines in methotrexate-induced learning and memory deficit. Canadian journal of physiology and pharmacology, 80(11), 1076-1084.
Naewla, S., Sirichoat, A., Pannangrong, W., Chaisawang, P., Wigmore, P., & Welbat, J. U. (2019). Hesperidin alleviates methotrexate-induced memory deficits via hippocampal neurogenesis in adult rats. Nutrients, 11(4), 936.
Reger, M. L., Hovda, D. A., & Giza, C. C. (2009). Ontogeny of rat recognition memory measured by the novel object recognition task. Developmental Psychobiology: The Journal of the International Society for Developmental Psychobiology, 51(8), 672-678.
Seigers, R., Schagen, S. B., Beerling, W., Boogerd, W., Van Tellingen, O., Van Dam, F. S., Koolhaas, J. M., & Buwalda, B. (2008). Long-lasting suppression of hippocampal cell proliferation and impaired cognitive performance by methotrexate in the rat. Behavioural brain research, 186(2), 168-175.
Seigers, R., Schagen, S. B., Coppens, C. M., van der Most, P. J., van Dam, F. S., Koolhaas, J. M., & Buwalda, B. (2009). Methotrexate decreases hippocampal cell proliferation and induces memory deficits in rats. Behavioural brain research, 201(2), 279-284.
Sritawan, N., Prajit, R., Chaisawang, P., Sirichoat, A., Pannangrong, W., Wigmore, P., & Welbat, J. U. (2020). Metformin alleviates memory and hippocampal neurogenesis decline induced by methotrexate chemotherapy in a rat model. Biomedicine & Pharmacotherapy, 131, 110651.
Sritawan, N., Suwannakot, K., Naewla, S., Chaisawang, P., Aranarochana, A., Sirichoat, A., Pannangrong, W., Wigmore, P., & Welbat, J. U. (2021). Effect of metformin treatment on memory and hippocampal neurogenesis decline correlated with oxidative stress induced by methotrexate in rats. Biomedicine & Pharmacotherapy, 144, 112280.
Vijayanathan, V., Gulinello, M., Ali, N., & Cole, P. D. (2011). Persistent cognitive deficits, induced by intrathecal methotrexate, are associated with elevated CSF concentrations of excitotoxic glutamate analogs and can be reversed by an NMDA antagonist. Behavioural brain research, 225(2), 491-497.
Wilks, M. J., Tie, M. L., & Pozza, C. H. (2002). CT and MRI appearances of methotrexate leucoencephalopathy. Australasian radiology, 46(1), 80-83.
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