Document Detail


Neurotoxicity of methotrexate to hippocampal cells in vivo and in vitro.
MedLine Citation:
PMID:  21459079     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
This study investigated whether methotrexate (MTX) is neurotoxic to neural progenitor cells in the hippocampus of adult mice and whether it affects hippocampus-dependent behaviors. In addition, the cytotoxicity of MTX was elucidated in rat immature and mature hippocampal cultured cells. The number of Ki-67 (proliferating cell marker)- and doublecortin (immature progenitor neuron marker)-positive cells were significantly time- and dose-dependently changed in the dentate gyrus of adult hippocampi after MTX treatment. A learning and memory task (object recognition memory test) and depression-like behavior test (tail-suspension test) were performed after MTX treatment to assess hippocampal neurogenesis-related behavioral dysfunction. MTX-treated mice showed significant depression-like behaviors and memory defects. The cytotoxicity of MTX in immature hippocampal cells varied in a dose-dependent pattern, but was not changed in the mature cells. MTX induced marked apoptotic changes in immature hippocampal cells, with increases in active caspase-3 and cleaved poly (ADP-ribose) polymerase expressions. Results of this study suggest that the neurotoxic effect of MTX inhibits the proliferation of hippocampal progenitor cells and can cause hippocampal dysfunction, such as depression and cognitive impairment. Additionally, the significantly greater caspase-dependent MTX sensitivity of immature hippocampal cells suggests that the susceptibility of such hippocampal cells depends on their maturation.
Authors:
Miyoung Yang; Joong-Sun Kim; Juhwan Kim; Sung-Ho Kim; Jong-Choon Kim; Jinwook Kim; Hongbing Wang; Taekyun Shin; Changjong Moon
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-31
Journal Detail:
Title:  Biochemical pharmacology     Volume:  -     ISSN:  1873-2968     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-4-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Affiliation:
Departments of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.
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