Apoptotic Process Induced by Oxaliplatin in Rat Hippocampus Causes Memory Impairment

Enrica Bianchi; Lorenzo Di Cesare Mannelli; Laura Micheli; Mersedez Farzad; Margherita Aglianò; Carla Ghelardini

doi:10.1111/bcpt.12629

Apoptotic Process Induced by Oxaliplatin in Rat Hippocampus Causes Memory Impairment

Basic Clin Pharmacol Toxicol. 2017 Jan;120(1):14-21. doi: 10.1111/bcpt.12629. Epub 2016 Aug 10.

Authors

Enrica Bianchi¹, Lorenzo Di Cesare Mannelli², Laura Micheli², Mersedez Farzad³, Margherita Aglianò¹, Carla Ghelardini²

Affiliations

¹ Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
² Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Unit, University of Florence, Florence, Italy.
³ Oncology Unit, Healthcare Institution Tuscan Southeast, Siena, Italy.

PMID: 27273873
DOI: 10.1111/bcpt.12629

Abstract

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.

MeSH terms

Absorption, Physiological / drug effects
Animals
Antidotes / administration & dosage
Antidotes / adverse effects
Antidotes / pharmacology
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Antineoplastic Agents / poisoning*
Apoptosis / drug effects*
Avoidance Learning / drug effects
Behavior, Animal / drug effects
Cell Line
Cells, Cultured
Cognition / drug effects
Copper Sulfate / administration & dosage
Copper Sulfate / adverse effects
Copper Sulfate / pharmacology
Exploratory Behavior / drug effects
Hippocampus / drug effects*
Hippocampus / pathology
Injections, Intraperitoneal
Injections, Intraventricular
Male
Memory Disorders / chemically induced*
Memory Disorders / prevention & control
Neurons / drug effects*
Neurons / pathology
Organoplatinum Compounds / administration & dosage
Organoplatinum Compounds / antagonists & inhibitors
Organoplatinum Compounds / pharmacology
Organoplatinum Compounds / poisoning*
Oxaliplatin
Random Allocation
Rats
Social Learning / drug effects

Substances

Antidotes
Antineoplastic Agents
Organoplatinum Compounds
Oxaliplatin
Copper Sulfate