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Neuropharmacology. 2014 Apr;79:234-48. doi: 10.1016/j.neuropharm.2013.11.012. Epub 2013 Dec 1.

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

Author information

  • 1Inserm U982, Laboratory of Neuronal and Neuroendocrine Communication and Differentiation (DC2N), Astrocyte and Vascular Niche, Institute of Research and Biomedical Innovation (IRIB), Normandy University PRES, University of Rouen, 76821 Mont-Saint-Aignan Cedex, France; North-West Cancéropole (CNO), 59008 Lille Cedex, France.
  • 2Inserm U982, Laboratory of Neuronal and Neuroendocrine Communication and Differentiation (DC2N), Astrocyte and Vascular Niche, Institute of Research and Biomedical Innovation (IRIB), Normandy University PRES, University of Rouen, 76821 Mont-Saint-Aignan Cedex, France.
  • 3EA4700, Laboratory of Psychology and Neurosciences of Cognition and Affectivity (PSY-NCA), University of Rouen, 76821 Mont-Saint-Aignan Cedex, France.
  • 4EA4700, Laboratory of Psychology and Neurosciences of Cognition and Affectivity (PSY-NCA), University of Rouen, 76821 Mont-Saint-Aignan Cedex, France; North-West Cancéropole (CNO), 59008 Lille Cedex, France.
  • 5Centre François Baclesse, Caen, France; Centre Hospitalo-Universitaire, Caen, France; North-West Cancéropole (CNO), 59008 Lille Cedex, France.
  • 6Inserm U982, Laboratory of Neuronal and Neuroendocrine Communication and Differentiation (DC2N), Astrocyte and Vascular Niche, Institute of Research and Biomedical Innovation (IRIB), Normandy University PRES, University of Rouen, 76821 Mont-Saint-Aignan Cedex, France; North-West Cancéropole (CNO), 59008 Lille Cedex, France. Electronic address: helene.castel@univ-rouen.fr.

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 chemotherapy 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.

Copyright © 2013 Elsevier Ltd. All rights reserved.

KEYWORDS:

Aging; Chemotherapy; Executive functions; Glucose; Hippocampal proliferating cells; Mouse

PMID:
24291465
[PubMed - indexed for MEDLINE]
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