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Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
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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
PubMed
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.

Keywords:
Blood vesselsChemotherapyImmunohistochemistryInflammationMouseNeurogenesis

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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.