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

Behav Brain Res. 2017 Jan 1:316:215-224. doi: 10.1016/j.bbr.2016.08.039. Epub 2016 Sep 4.

Abstract

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.

Keywords: 5-Fluorouracil; Chemokines; Cytokines; Dendritic spines; Hippocampus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging* / drug effects
  • Animals
  • Dendrites / drug effects*
  • Dendrites / metabolism*
  • Dendrites / ultrastructure
  • Dendritic Spines / ultrastructure
  • Fluorouracil / pharmacology*
  • Hippocampus / cytology*
  • Immunosuppressive Agents / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Silver Staining
  • Up-Regulation / drug effects*

Substances

  • Immunosuppressive Agents
  • Fluorouracil