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AMP-activated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation

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Abstract

Adenosine monophosphate-activated protein kinase (AMPK) is a member of metabolite-sensing kinase family that plays important roles in responses of muscle cells to metabolic stress. AMPK is a heterotrimer of a catalytic α subunit (α1 or α2), and β (β1 or β2) and γ (γ1 or γ2) subunits. Because the brain has a high metabolic rate and is sensitive to changes in the supply of glucose and oxygen, we investigated the expression of AMPK in rat embryonic and adult brain and its role in modifying neuronal survival under conditions of cellular stress. We report that catalytic (α1 and α2) and noncatalytic (β2 and γ1) subunits of AMPK are present at high levels in embryonic hippocampal neurons in vivo and in cell culture. In the adult rat brain, the catalytic subunits α1 and α2 are present in neurons throughout the brain. The AMPK-activating agent AICAR protected hippocampal neurons against death induced by glucose deprivation, chemical hypoxia, and exposure to glutamate and amyloid β-peptide. Suppression of levels of the AMPK α1 and α2 subunits using antisense technology resulted in enhanced neuronal death following glucose deprivation, and abolished the neuroprotective effect of AICAR. These findings suggest that AMPK can protect neurons against metabolic and excitotoxic insults relevant to the pathogenesis of several different neurodegenerative conditions.

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Authors and Affiliations

  1. Laboratory of Neurosciences, National Institute on Aging, 5600 Nathan Shock Drive, 21224, Baltimore, MD

    Carsten Culmsee & Mark P. Mattson

  2. Institut für Pharmakologie und Toxikologie, Philipps-Universität Marburg, D-35037, Marburg, Germany

    Carsten Culmsee

  3. Sanders-Brown Research Center on Aging, University of Kentucky, 40536, Lexington, KY

    Jennifer Monnig & Mark P. Mattson

  4. St. Vincent’s Institute of Medical Research, St. Vincent’s Hospital, 3065, Fitzroy, Vic, Australia

    Bruce E. Kemp

  5. Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe, Street, 21205, Baltimore, MD

    Mark P. Mattson

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  1. Carsten Culmsee
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  2. Jennifer Monnig
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  3. Bruce E. Kemp
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  4. Mark P. Mattson
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Correspondence to Mark P. Mattson.

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Culmsee, C., Monnig, J., Kemp, B.E. et al. AMP-activated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation. J Mol Neurosci 17, 45–58 (2001). https://doi.org/10.1385/JMN:17:1:45

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  • DOI: https://doi.org/10.1385/JMN:17:1:45

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