Evaluation of the Impact of the Cancer Therapy Everolimus on the Central Nervous System in Mice
| Autor: | Pascal Hilber, Marie-Christine Tonon, Martine Dubois, Youssef Anouar, François Proust, Pierrick Gandolfo, Vadim Le Joncour, Florence Joly, Hélène Castel, Fabrice Morin |
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| Přispěvatelé: | Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Hautepierre [Strasbourg], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Psychologie et Neurosciences de la Cognition et de l'affectivité (PSY-NCA), Normandie Université (NU)-Normandie Université (NU), Neuroendocrinologie cellulaire et moléculaire, Service de neurochirurgie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'Oncologie médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Recherches sur les Fonctionnements et Dysfonctionnements Psychologiques (CRFDP), Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Central Nervous System
Male medicine.medical_treatment [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology [SDV]Life Sciences [q-bio] Hippocampus [SHS.PSY]Humanities and Social Sciences/Psychology Pharmacology Hippocampal formation Mice Behavioral Neuroscience [SCCO]Cognitive science Cognition Learning and Memory Neural Stem Cells Medicine and Health Sciences Cells Cultured ComputingMilieux_MISCELLANEOUS Multidisciplinary [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior Ribosomal Protein S6 Kinases 70-kDa [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences 3. Good health medicine.anatomical_structure Oncology Hypothalamus [SCCO.PSYC]Cognitive science/Psychology Medicine Research Article medicine.drug Science Central nervous system Antineoplastic Agents [SDV.CAN]Life Sciences [q-bio]/Cancer [SDV.BC]Life Sciences [q-bio]/Cellular Biology Electron Transport Complex IV medicine [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] Animals Learning Everolimus PI3K/AKT/mTOR pathway Cell Proliferation Sirolimus Chemotherapy business.industry [SCCO.NEUR]Cognitive science/Neuroscience Endothelial Cells Biology and Life Sciences Cancer medicine.disease Mice Inbred C57BL [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology business Neuroscience |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2014, 9 (12), pp.e113533. ⟨10.1371/journal.pone.0113533⟩ PLoS ONE, Vol 9, Iss 12, p e113533 (2014) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0113533⟩ |
| Popis: | International audience; Cancer and treatments may induce cognitive impairments in cancer patients, and the causal link between chemotherapy and cognitive dysfunctions was recently validated in animal models. New cancer targeted therapies have become widely used, and their impact on brain functions and quality of life needs to be explored. We evaluated the impact of everolimus, an anticancer agent targeting the mTOR pathway, on cognitive functions, cerebral metabolism, and hippocampal cell proliferation/vascular density in mice. Adult mice received everolimus daily for 2 weeks, and behavioral tests were performed from 1 week after the last treatment. Everolimus-treated mice displayed a marked reduction in weight gain from the last day of the treatment period. Ex vivo analysis showed altered cytochrome oxidase activity in selective cerebral regions involved in energy balance, food intake, reward, learning and memory modulation, sleep/wake cycle regulation, and arousal. Like chemotherapy, everolimus did not alter emotional reactivity, learning and memory performances, but in contrast to chemotherapy, did not affect behavioral flexibility or reactivity to novelty. In vivo hippocampal neural cell proliferation and vascular density were also unchanged after everolimus treatments. In conclusion, two weeks daily everolimus treatment at the clinical dose did not evoke alteration of cognitive performances evaluated in hippocampal- and prefrontal cortex-dependent tasks that would persist at one to four weeks after the end of the treatment completion. However, acute everolimus treatment caused selective CO modifications without altering the mTOR effector P70S6 kinase in cerebral regions involved in feeding behavior and/or the sleep/wake cycle, at least in part under control of the solitary nucleus and the parasubthalamic region of the hypothalamus. Thus, this area may represent a key target for everolimus-mediating peripheral modifications, which has been previously associated with symptoms such as weight loss and fatigue. |
| Databáze: | OpenAIRE |
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