Get access

Acetoacetate protects neuronal cells from oxidative glutamate toxicity

Authors

  • Hae Sook Noh,

    1. Department of Anatomy and Neurobiology, Institute of Health Science, College of Medicine,Gyeongsang National University, Kyungnam, South Korea
    Search for more papers by this author
    • The first two authors contributed equally to this work.

  • Young-Sool Hah,

    1. Department of Biochemistry, College of Medicine, Gyeongsang National University,Kyungnam, South Korea
    Search for more papers by this author
    • The first two authors contributed equally to this work.

  • Rashidova Nilufar,

    1. Department of Anatomy and Neurobiology, Institute of Health Science, College of Medicine,Gyeongsang National University, Kyungnam, South Korea
    Search for more papers by this author
  • Jaehee Han,

    1. Department of physiology, College of Medicine, Gyeongsang National University,Kyungnam, South Korea
    Search for more papers by this author
  • Jae-Hwan Bong,

    1. Department of Anatomy and Neurobiology, Institute of Health Science, College of Medicine,Gyeongsang National University, Kyungnam, South Korea
    Search for more papers by this author
  • Sang Soo Kang,

    1. Department of Anatomy and Neurobiology, Institute of Health Science, College of Medicine,Gyeongsang National University, Kyungnam, South Korea
    Search for more papers by this author
  • Gyeong Jae Cho,

    1. Department of Anatomy and Neurobiology, Institute of Health Science, College of Medicine,Gyeongsang National University, Kyungnam, South Korea
    Search for more papers by this author
  • Wan Sung Choi

    Corresponding author
    1. Department of Anatomy and Neurobiology, Institute of Health Science, College of Medicine,Gyeongsang National University, Kyungnam, South Korea
    • Department of Anatomy and Neurobiology, College of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Kyungnam 660-751, South Korea
    Search for more papers by this author

Abstract

Glutamate cytotoxicity contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. We previously reported that a high-fat and low-carbohydrate diet, the ketogenic diet (KD), protects against kainic acid-induced hippocampal cell death in mice. We hypothesized based on these findings that ketosis resulting from KD might inhibit glutamate cytotoxicity, resulting in inhibition of hippocampal neuronal cell death. Therefore, we investigated the role of ketone bodies [acetoacetate (AA) and β-hydroxybutyrate (β-OHB)] both in a mouse hippocampal cell line (HT22) and in rat primary hippocampal neurons. As a result, we found that pretreatment with 5 mM lithium AA and 4 mM Na β-OHB protected the HT22 hippocampal cell line and primary hippocampal neuronal culture against 5 mM glutamate toxicity and that up to 2 hr of pretreatment with 5 mM AA had a protective effect against 5 mM glutamate toxicity in the HT22 cell line. Pretreatment with 5 mM AA decreased ROS production of HT22 cell line at 2 and 8 hr exposure of glutamate, and it decreased the appearance of annexin V-positive HT22 cells, which are indicative of an early stage of apoptosis, and propidium iodide-positive HT22 cells, which are indicative of necrosis. © 2006 Wiley-Liss, Inc.

Get access to the full text of this article

Ancillary