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 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.