Assessing the effects of redox modifier MnTnBuOE-2-PyP 5+ on cognition and hippocampal physiology following doxorubicin, cyclophosphamide, and paclitaxel treatment

Taylor McElroy, Taurean Brown, Fred Kiffer, Jing Wang, Stephanie D. Byrum, Rebecca E. Oberley-Deegan, Antiño R. Allen

Research output: Contribution to journalArticle

Abstract

Background: Chemotherapy treatment for breast cancer can induce cognitive impairments often involving oxidative stress. The brain, as a whole, is susceptible to oxidative stress due to its high-energy requirements, limited anaerobic respiration capacities, and limited antioxidant defenses. The goal of the current study was to determine if the manganese porphyrin superoxide dismutase mimetic MnTnBuOE-2-PyP (MnBuOE) could ameliorate the effects of doxorubicin, cyclophosphamide, and paclitaxel (AC-T) on mature dendrite morphology and cognitive function. Methods: Four-month-old female C57BL/6 mice received intraperitoneal injections of chemotherapy followed by subcutaneous injections of MnBuOE. Four weeks following chemotherapy treatment, mice were tested for hippocampus-dependent cognitive performance in the Morris water maze. After testing, brains were collected for Golgi staining and molecular analyses. Results: MnBuOE treatment preserved spatial memory during the Morris water-maze. MnBuOE/AC-T showed spatial memory retention during all probe trials. AC-T treatment significantly impaired spatial memory retention in the first and third probe trial (no platform). AC-T treatment decreased dendritic length in the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) areas of the hippocampus while AC-T/MnBuOE maintained dendritic length. Comparative proteomic analysis revealed affected protein networks associated with cell morphology and behavior functions in both the AC-T and AC-T/MnBuOE treatment groups.

Original languageEnglish (US)
Article number1867
JournalInternational journal of molecular sciences
Volume21
Issue number5
DOIs
StatePublished - Mar 1 2020

Keywords

  • Cognition
  • Cyclophosphamide
  • Doxorubicin
  • Hippocampus
  • MnTnBuOE-2-PyP
  • Paclitaxel

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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