Gene expression dynamics following mithramycin treatment: A possible model for post‐chemotherapy cognitive impairment

Summary Chemotherapy‐induced cognitive changes is a major burden on a substantial number of cancer survivors. The mechanism of this sequel is unknown. In this study, we followed long‐term effects of early in life mithramycin (MTR) treatment on behaviour and on the normal course of alterations of gen...

Full description

Saved in:
Bibliographic Details
Published in:Clinical and experimental pharmacology & physiology 2018-10, Vol.45 (10), p.1028-1037
Main Authors: Asor, Eyal, Ben‐Shachar, Dorit
Format: Article
Language:English
Subjects:
Abnormalities
Brain
Cancer
chemobrain
Chemotherapy
Cognitive ability
cognitive impairment
Cortex (frontal)
Gene expression
gene expression dynamics
Genes
Long-term effects
mithramycin
Prefrontal cortex
rat
Rats
Short term memory
Spatial memory
Time dependence
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Chemotherapy‐induced cognitive changes is a major burden on a substantial number of cancer survivors. The mechanism of this sequel is unknown. In this study, we followed long‐term effects of early in life mithramycin (MTR) treatment on behaviour and on the normal course of alterations of gene expression in brain. Between post‐natal days (PND) 7 and 10, male rats were divided into 2 groups, 1 receiving MTR (0.1 mg/kg s.c. per day) and the other receiving saline. At PND11, frontal cortex tissue samples were dissected from 4 rats from each group. At PND 65 the remaining rats underwent behavioural tests after which all the rats were decapitated and their prefrontal cortex incised. Rats treated transiently with MTR early in life, showed impairments in spatial working memory and anxious‐like behaviour in adulthood. The immediate molecular effect of MTR was expressed in a limited number of altered genes of different unconnected trajectories, which were simultaneously distorted by the drug. In contrast, 3 months later we observed a change in the expression of more than 1000 genes that converged into specific cellular processes. Time‐dependent gene expression dynamics of several genes was significantly different between treated and untreated rats. The differences in the total number of altered genes and in gene expression trends, immediately and long after MTR treatment cessation, suggest the evolution of a new cellular homeostatic set point, which can lead to behavioural abnormalities following chemotherapy treatment.
ISSN:0305-1870
1440-1681
DOI:10.1111/1440-1681.12975