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Chemotherapy-induced long-term alteration of executive functions and hippocampal cell proliferation: Role of glucose as adjuvant

Abstract : In patients, cancer and treatments provoke cognitive impairments referred to "chemofog". Here a validated neurobehavioral animal model, the unique way to explore causal direct links between chemo-therapy used in clinical practices and brain disorders, allowed investigation of the direct long-term impact of colo-rectal cancer chemotherapy on cognition and cerebral plasticity. Young and aged mice received three injections every 7 days during 2 weeks of 5-fluorouracil either alone (5-FU, 37.5 mg/kg) or in combination with oxaliplatin (3 mg/kg) or with glucose (5%). The long-term effects (from day 24 to day 60) of chemotherapy were tested on emotional reactivity, learning and memory, behavioral flexibility and hippocampal cell plasticity. 5-FU (in saline)-treated aged and also young mice exhibited specific altered cognitive flexibility and behavioral hyper-reactivity to novelty, whereas the combination 5-FU (in saline)/oxaliplatin (in glucose) did not provoke any cognitive dysfunction. We thus observed that glucose counteracted 5-FU-induced altered executive functions and hippocampal cell proliferation in vivo, and protected neural stem cells in vitro from toxicity of 5-FU or oxaliplatin. In conclusion, these data suggest that the lasting chemotherapy-induced selective impairment of executive functions, whatever the age, and associated with a reduced number of hippocampal proliferating cells, can be counteracted by co-administration with glucose.
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Submitted on : Monday, January 13, 2020 - 12:05:26 PM
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M. Dubois, N. Lapinte, V. Villier, C. Lecointre, V. Roy, et al.. Chemotherapy-induced long-term alteration of executive functions and hippocampal cell proliferation: Role of glucose as adjuvant. Neuropharmacology, Elsevier, 2014, 79, pp.234-248. ⟨10.1016/j.neuropharm.2013.11.012⟩. ⟨hal-02355815⟩

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