Apoptotic Process Induced by Oxaliplatin in Rat Hippocampus Causes Memory Impairment.
Aspects of memory involved in cognitive mechanisms were investigated in rat after oxaliplatin (OX) chemotherapy using animal behavioural assessment of passive avoidance and social learning paradigms, which are both hippocampus-sensitive. Rodents, previously subjected to 2-week OX treatment, showed passive avoidance and social learning impairment and apoptotic processes in the hippocampus. Apoptosis rate significantly increased in cultured hippocampal cells exposed to OX at increasing doses, and this effect was dose-dependent. Ex vivo experiments showed that cell damage and apoptosis were blocked in the hippocampus from OX rats cotreated with copper sulphate (CS) which precludes OX transport inside the cell. In vivo, passive avoidance and social learning impairment could not be observed in OX rats co-administered with CS. Thus, a site of action of OX treatment on memory impairment appears to be located at the hippocampus. These findings strongly support that cellular damage induced by OX in rodent hippocampus underlies the weakening of some memory functions.
Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Enrica
E
Bianchi
Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Unit, University of Florence, Florence, Italy.
Lorenzo
L
Di Cesare Mannelli
Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Unit, University of Florence, Florence, Italy.
Laura
L
Micheli
Oncology Unit, Healthcare Institution Tuscan Southeast, Siena, Italy.
Mersedez
M
Farzad
Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Margherita
M
Aglianò
Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Unit, University of Florence, Florence, Italy.
Carla
C
Ghelardini
D065567:Absorption, Physiological / Q000187:drug effects; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000506:poisoning*; D017209:Apoptosis / Q000187:drug effects*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects; D019327:Copper Sulfate / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000506:poisoning*; D000077150:Oxaliplatin; D011897:Random Allocation; D051381:Rats; D000067570:Social Learning / Q000187:drug effects
D000931:Antidotes; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D019327:Copper Sulfate