Enhanced hippocampus-dependent memory and reduced anxiety in mice over-expressing human catalase in mitochondria

Authors

  • Reid H. J. Olsen,

    1. Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA
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  • Lance A. Johnson,

    1. Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA
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  • Damian G. Zuloaga,

    1. Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA
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  • Charles L. Limoli,

    1. Department of Radiation Oncology and Cancer Research Institute, University of California, Irvine, California, USA
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  • Jacob Raber

    Corresponding author
    1. Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA
    2. Division of Neuroscience, ONPRC, Oregon Health & Science University, Beaverton, Oregon, USA
    • Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA
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Address correspondece and reprint requests to Jacob Raber, PhD, Dept of Behavioral Neuroscience, L470, Oregon Health and Science University, 3181 SW Sam Jackson Pkwy, Portland, OR 97239, USA. E-mail: raberj@ohsu.edu

Abstract

Oxidative stress (OS) and reactive oxygen species (ROS) play a modulatory role in synaptic plasticity and signaling pathways. Mitochondria (MT), a major source of ROS because of their involvement in energy metabolism, are important for brain function. MT-generated ROS are proposed to be responsible for a significant proportion of OS and are associated with developmental abnormalities and aspects of cellular aging. The role of ROS and MT function in cognition of healthy individuals is relatively understudied. In this study, we characterized behavioral and cognitive performance of 5- to 6-month-old mice over-expressing mitochondrial catalase (MCAT). MCAT mice showed enhancements in hippocampus-dependent spatial learning and memory in the water maze and contextual fear conditioning, and reduced measures of anxiety in the elevated zero maze. Catalase activity was elevated in MCAT mice in all brain regions examined. Measures of oxidative stress (glutathione, protein carbonyl content, lipid peroxidation, and 8-hydroxyguanine) did not significantly differ between the groups. The lack of differences in these markers of oxidative stress suggests that the differences observed in this study may be due to altered redox signaling. Catalase over-expression might be sufficient to enhance cognition and reduce measures of anxiety even in the absence of alteration in levels of OS.

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