Inhibition of hippocampal cell proliferation by methotrexate in rats is not potentiated by the presence of a tumor.
Brain Research Bulletin. 2010-03-01; 81(4-5): 472-476
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1. Brain Res Bull. 2010 Mar 16;81(4-5):472-6. doi:
10.1016/j.brainresbull.2009.10.006. Epub 2009 Oct 12.
Inhibition of hippocampal cell proliferation by methotrexate in rats is not
potentiated by the presence of a tumor.
Seigers R(1), Pourtau L, Schagen SB, van Dam FS, Koolhaas JM, Konsman JP, Buwalda
(1)Department of Behavioral Physiology, University of Groningen, NN Haren, The
Netherlands. *protected email*
Methotrexate is a widely used cytostatic in chemotherapy cocktails for the
treatment of cancer but is associated with cognitive impairment. Previous animal
studies indicated that methorexate decreases hippocampal cell proliferation,
which might contribute to the observed cognitive impairment. However, clinical
studies have shown that cognitive impairment can also be noticed in some cancer
patients before any systemic treatment is initiated. We aim in the present study
to discern whether hippocampal cell proliferation is negatively affected by tumor
growth and if the presence of a tumor amplifies the effects of methotrexate.
Buffalo rats were subcutaneously injected with PBS or Morris Hepatoma 7777 cells
to induce a tumor. Two weeks after this injection the animals received an
intraperitoneal injection of methotrexate or saline. Three weeks later
hippocampal cell proliferation was quantified using immunohistochemical staining.
Treatment with Morris Hepatoma 7777 cells decreased the number of proliferating
cells as compared to control animals. An overall tumor effect was absent mainly
because methotrexate treatment significantly decreased cell proliferation with no
differences between animals with or without a tumor. Neither methotrexate nor the
tumor induced pica behavior. These findings indicate that although the presence
of a tumor reduces hippocampal cell proliferation it does not affect the negative
effect of methotrexate on this plasticity marker. Since sickness behavior is not
induced by methotrexate or tumor presence it does not play a role in the
development of cognitive deficits. This study further indicates that the effects
of methotrexate on brain and behavior can be studied in healthy animals.
Copyright 2009 Elsevier Inc. All rights reserved.
PMID: 19828128 [Indexed for MEDLINE]