5-Fluorouracil chemotherapy upregulates cytokines and alters hippocampal dendritic complexity in aged mice

•5-Fu significantly compromised the dendritic architecture.•5-Fu decreased spine density and modulated spine morphology throughout Hippocampus.•5-Fu upregulated pro-inflammatory and anti-inflammatory cytokines. 5-Fluorouracil (5-Fu) is commonly used chemotherapy drug, but it can lead to the impairme...

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Bibliographic Details
Published in:Behavioural brain research 2017-01, Vol.316, p.215-224
Main Authors: Groves, Thomas R., Farris, Ryan, Anderson, Julie E., Alexander, Tyler C., Kiffer, Frederico, Carter, Gwendolyn, Wang, Jing, Boerma, Marjan, Allen, Antiño R.
Format: Article
Language:English
Subjects:
5-Fluorouracil
Aging - drug effects
Animals
Chemokines
Cytokines
Dendrites - drug effects
Dendrites - metabolism
Dendrites - ultrastructure
Dendritic spines
Dendritic Spines - ultrastructure
Fluorouracil - pharmacology
Hippocampus
Hippocampus - cytology
Immunosuppressive Agents - pharmacology
Male
Mice
Mice, Inbred C57BL
Silver Staining
Up-Regulation - drug effects
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Summary:•5-Fu significantly compromised the dendritic architecture.•5-Fu decreased spine density and modulated spine morphology throughout Hippocampus.•5-Fu upregulated pro-inflammatory and anti-inflammatory cytokines. 5-Fluorouracil (5-Fu) is commonly used chemotherapy drug, but it can lead to the impairment of cognitive function. The pathogenesis of this injury is unknown but may involve modifications to dendritic structure and/or alterations in dendritic spine density and morphology. Dendritic spines are sites of excitatory synaptic transmission and changes in spine structure and dendrite morphology are thought to represent a morphological correlate of altered brain functions associated with hippocampal dependent learning and memory. A total of 28 one-year-old C57BL6/J male mice were used in this study; 14 mice received 5-Fu treatment and 14 were given saline injections. One month post treatment, 14 cytokines were measured at the same time Golgi samples were taken. 8 analytes were significantly elevated in mice treated with 5-Fu. 5-Fu significantly compromised the dendritic architecture and reduced spine density throughout the hippocampal tri-synaptic network. The present data provide the evidence that 5-Fu has deleterious effects on mature neurons associated with hippocampal learning and memory.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2016.08.039