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Neurobiological changes by cytotoxic agents in mice
R Seigers1, M Loos2, O Van Tellingen3
1Department of Psychosocial Research and Epidemiology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
Behavioural Brain Research
|November 26, 2015
Summary
Chemotherapy agents did not impact neurogenesis in mice. Some agents increased blood vessel density and decreased microglia, suggesting mild inflammation, but effects were modest.
Area of Science:
- Neuroscience
- Pharmacology
- Oncology
Background:
- Chemotherapy-induced cognitive deficit is a common side effect.
- Neurobiological mechanisms are not fully understood due to varied study designs.
Purpose of the Study:
- To systematically investigate the neurobiological effects of six cytotoxic agents.
- To analyze impacts on neurogenesis, blood vessel density, and neuroinflammation.
Main Methods:
- C57Bl/6J mice treated with cyclophosphamide, docetaxel, doxorubicin, 5-fluorouracil, methotrexate, or topotecan.
- Analysis of neurogenesis, blood vessel density, and neuroinflammation via immunohistochemistry at 3 and 15 weeks.
- Secondary study using topotecan in FVB mice (wildtype and knockouts).
Main Results:
- No tested cytotoxic agents affected neurogenesis (cell survival or proliferation).
- Docetaxel and doxorubicin increased hippocampal and prefrontal cortex blood vessel density at 3 weeks.
- Cyclophosphamide, docetaxel, 5-fluorouracil, and topotecan decreased microglia in the prefrontal cortex, indicating inflammation.
Conclusions:
- Chemotherapy agents had modest effects on neurobiological parameters studied.
- FVB mice may be resistant to topotecan's neurotoxic effects, limiting their use in studying chemotherapy-induced cognitive impairment.
