PMID- 18702703
OWN - NLM
STAT- MEDLINE
DCOM- 20081023
LR  - 20240408
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Linking)
VI  - 28
IP  - 2
DP  - 2008 Jul
TI  - 5-Fluorouracil chemotherapy affects spatial working memory and newborn neurons in 
      the adult rat hippocampus.
PG  - 323-30
LID - 10.1111/j.1460-9568.2008.06325.x [doi]
AB  - Chemotherapy-associated memory deficits in adults are prevalent with systemic 
      treatment utilizing 5-fluorouracil (5-Fu). 5-Fu disrupts cell proliferation and 
      readily crosses the blood-brain barrier. Proliferating cells within the adult 
      dentate gyrus of the hippocampus give rise to new neurons involved in memory and 
      learning and require neurotrophic factors such as brain-derived neurotrophic 
      factor (BDNF) to nurture this process of adult neurogenesis. Some of these 
      proliferating cells are anatomically and functionally supported by vascular 
      endothelial cells. We propose that systemically administered 5-Fu chemotherapy 
      will cause deficits in hippocampal memory that are associated with altered BDNF 
      levels and proliferating cells (particularly vascular-associated cells) in the 
      dentate gyrus. This was tested by determining the effect of 5-Fu on spatial 
      working memory as modelled by the object location recognition test. Numbers of 
      vascular-associated (VA) and non-vascular-associated (NVA) proliferating cells in 
      the dentate gyrus were measured using double-labelling immunohistochemistry with 
      markers of proliferation (Ki67) and endothelial cells (RECA-1). 5-Fu-induced 
      changes in hippocampal BDNF and doublecortin (DCX) protein levels were quantified 
      using Western immunoblotting. 5-Fu chemotherapy caused a marginal disruption in 
      spatial working memory and did not alter the total proliferating cell counts or 
      the percentage of VA and NVA proliferating cells in the dentate gyrus. In 
      contrast, 5-Fu significantly reduced BDNF and DCX levels in the hippocampus, 
      indicating alterations in neurotrophin levels and neurogenesis. These findings 
      highlight the usefulness of animal models of 'chemobrain' for understanding the 
      mechanisms that underlie chemotherapy-associated declines in cognitive 
      performance and memory.
FAU - Mustafa, Sarah
AU  - Mustafa S
AD  - School of Biomedical Sciences, Institute of Neuroscience, University of 
      Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
FAU - Walker, Alex
AU  - Walker A
FAU - Bennett, Geoffrey
AU  - Bennett G
FAU - Wigmore, Peter M
AU  - Wigmore PM
LA  - eng
PT  - Journal Article
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dcx protein, rat)
RN  - 0 (Doublecortin Domain Proteins)
RN  - 0 (Doublecortin Protein)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Neuropeptides)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Animals
MH  - Antimetabolites, Antineoplastic/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/antagonists & inhibitors
MH  - Cell Count
MH  - Cell Proliferation/drug effects
MH  - Dentate Gyrus/cytology
MH  - Doublecortin Domain Proteins
MH  - Doublecortin Protein
MH  - Fluorouracil/*pharmacology
MH  - Hippocampus/cytology/*drug effects/metabolism
MH  - Immunohistochemistry
MH  - Male
MH  - Microtubule-Associated Proteins/antagonists & inhibitors
MH  - Neurons/*drug effects
MH  - Neuropeptides/antagonists & inhibitors
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Recognition, Psychology/*drug effects
MH  - Space Perception/*drug effects
MH  - Weight Gain/drug effects
EDAT- 2008/08/16 09:00
MHDA- 2008/10/24 09:00
CRDT- 2008/08/16 09:00
PHST- 2008/08/16 09:00 [pubmed]
PHST- 2008/10/24 09:00 [medline]
PHST- 2008/08/16 09:00 [entrez]
AID - EJN6325 [pii]
AID - 10.1111/j.1460-9568.2008.06325.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2008 Jul;28(2):323-30. doi: 10.1111/j.1460-9568.2008.06325.x.