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Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2’s neurotrophic effects?

  • Gregory J Moore
    Correspondence
    Address reprint requests to Gregory J. Moore, Ph.D., Wayne State University School of Medicine, Dept. of Psychiatry and Behavioral Neurosciences, 4201 St. Antoine UHC 9B-28, Detroit MI 48201
    Affiliations
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, JMB, KH, GC, NS-B, IBW, MWF, SK, DAG, LJ, HKM)

    Department of Radiology, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM)

    Cellular and Clinical Neurobiology Program, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, HKM)
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  • Joseph M Bebchuk
    Affiliations
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, JMB, KH, GC, NS-B, IBW, MWF, SK, DAG, LJ, HKM)
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  • Khondakar Hasanat
    Affiliations
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, JMB, KH, GC, NS-B, IBW, MWF, SK, DAG, LJ, HKM)
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  • Guang Chen
    Affiliations
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, JMB, KH, GC, NS-B, IBW, MWF, SK, DAG, LJ, HKM)
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  • Navid Seraji-Bozorgzad
    Affiliations
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, JMB, KH, GC, NS-B, IBW, MWF, SK, DAG, LJ, HKM)
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  • Ian B Wilds
    Affiliations
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, JMB, KH, GC, NS-B, IBW, MWF, SK, DAG, LJ, HKM)
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  • Michael W Faulk
    Affiliations
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, JMB, KH, GC, NS-B, IBW, MWF, SK, DAG, LJ, HKM)
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  • Susanne Koch
    Affiliations
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, JMB, KH, GC, NS-B, IBW, MWF, SK, DAG, LJ, HKM)
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  • Debra A Glitz
    Affiliations
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, JMB, KH, GC, NS-B, IBW, MWF, SK, DAG, LJ, HKM)
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  • Libby Jolkovsky
    Affiliations
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, JMB, KH, GC, NS-B, IBW, MWF, SK, DAG, LJ, HKM)
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  • Husseini K Manji
    Affiliations
    Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, JMB, KH, GC, NS-B, IBW, MWF, SK, DAG, LJ, HKM)

    Department of Pharmacology, Wayne State University School of Medicine, Detroit, MichiganUSA (HKM)

    Cellular and Clinical Neurobiology Program, Wayne State University School of Medicine, Detroit, MichiganUSA (GJM, HKM)
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      Abstract

      Background: Recent preclinical studies have shown that lithium (Li) robustly increases the levels of the major neuroprotective protein, bcl-2, in rat brain and in cells of human neuronal origin. These effects are accompanied by striking neuroprotective effects in vitro and in the rodent central nervous system in vivo. We have undertaken the present study to determine if lithium exerts neurotrophic/neuroprotective effects in the human brain in vivo.
      Methods: Using quantitative proton magnetic resonance spectroscopy, N-acetyl-aspartate (NAA) levels (a putative marker of neuronal viability and function) were investigated longitudinally in 21 adult subjects (12 medication-free bipolar affective disorder patients and 9 healthy volunteers). Regional brain NAA levels were measured at baseline and following 4 weeks of lithium (administered in a blinded manner).
      Results: A significant increase in total brain NAA concentration was documented (p < .0217). NAA concentration increased in all brain regions investigated, including the frontal, temporal, parietal, and occipital lobes.
      Conclusions: This study demonstrates for the first time that Li administration at therapeutic doses increases brain NAA concentration. These findings provide intriguing indirect support for the contention that chronic lithium increases neuronal viability/function in the human brain, and suggests that some of Li’s long-term beneficial effects may be mediated by neurotrophic/neuroprotective events.

      Keywords

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