Apoptotic Process Induced by Oxaliplatin in Rat Hippocampus Causes Memory Impairment

• DOI: 10.1111/bcpt.12629
• Publication Date: 2016-06-06T15:08:49Z
• Authors: Enrica Bianchi; Lorenzo Di Cesare...; Laura Micheli; Mersedez Farzad; Margherita Aglianò; Carla Ghelardini
• Keywords: Male; 0301 basic medicine; Copper Sulfate; Organoplatinum Compounds; Physiological; Cells; Intraventricular; Antidotes; Antineoplastic Agents; Apoptosis; Hippocampus; Absorption; Injections; Cell Line; Antineoplastic Agent; Random Allocation; 03 medical and health sciences; Hippocampu; Cognition; 0302 clinical medicine; Avoidance Learning; Animals; Intraperitoneal; Cells, Cultured; Injections, Intraventricular; Neurons; Behavior; Memory Disorders; Cultured; Behavior, Animal; Animal; Absorption, Physiological; Animals; Antidotes; Antineoplastic Agents; Apoptosis; Avoidance Learning; Behavior, Animal; Cell Line; Cells, Cultured; Cognition; Copper Sulfate; Exploratory Behavior; Hippocampus; Injections, Intraperitoneal; Injections, Intraventricular; Male; Memory Disorders; Neurons; Organoplatinum Compounds; Oxaliplatin; Random Allocation; Rats; Social Learning; Organoplatinum Compound; Apoptosi; Neuron; Social Learning; Absorption, Physiological; Oxaliplatin; Medicine (all); Toxicology; Pharmacology; Antidote; Exploratory Behavior; Rat; Injections, Intraperitoneal; Memory Disorder

AbstractAspects 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.