5-Fluorouracil chemotherapy upregulates cytokines and alters hippocampal dendritic complexity in aged mice.
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.
Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Thomas R
TR
Groves
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Ryan
R
Farris
Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Julie E
JE
Anderson
Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Tyler C
TC
Alexander
Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Frederico
F
Kiffer
Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Gwendolyn
G
Carter
Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Jing
J
Wang
Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Marjan
M
Boerma
Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: AAllen@uams.edu.
Antiño R
AR
Allen
D000375:Aging / Q000187:drug effects; D000818:Animals; D003712:Dendrites / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D049229:Dendritic Spines / Q000648:ultrastructure; D005472:Fluorouracil / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016622:Silver Staining; D015854:Up-Regulation / Q000187:drug effects*
D007166:Immunosuppressive Agents; D005472:Fluorouracil
5-Fluorouracil; Chemokines; Cytokines; Dendritic spines; Hippocampus