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Cortical Spreading Depression Increases the Phosphorylation of AMP-Activated Protein Kinase in the Cerebral Cortex

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Abstract

Cortical spreading depression (CSD) enhances ischemic tolerance to temporary focal ischemia. Although this effect most likely requires the expression or activation of neuroprotective factors, their identity remains relatively unknown. One important factor involved in neuroprotection is adenosine monophosphate-dependent kinase (AMPK), a serine/threonine kinase that is activated via phosphorylation. This activation occurs in response to brain ischemia, hypoxia, or glucose deprivation. Thus, to determine the potential mechanism of the neuroprotective effects of CSD, we tested whether AMPK becomes phosphorylated into phospho-AMP-activated protein kinase (pAMPK) after CSD. CSD was induced for 15 min in three groups of five rats. The animals were subsequently sacrificed after 2, 4 or 24 h. Western blot analyses were performed to determine the AMPKα and pAMPKα levels in the cortex (right and left hemispheres), and immunohistochemistry and immunofluorescence were performed to determine the localisation of AMPKα and pAMPKα in the cerebral cortex. These results demonstrated a significant increase in pAMPKα at 24 h (but not at 2 and 4 h) after CSD. In contrast, un-phosphorylated AMPK expression did not change. The increase in pAMPKα was confined to neurons (predominantly neurons located in the superficial layers of the cerebral cortex) and was not observed in astroglial cells. Taken together, these data indicate that AMPK is activated by CSD, and suggest that this activation may contribute to the neuroprotective effect of CSD.

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Authors and Affiliations

  1. Department of Experimental Medicine – Section of Human Physiology, Second University of Naples, Via De Crecchio 8, 80138, Naples, Italy

    Emanuela Viggiano, Davide Viggiano, Alessandro Viggiano, Bruno De Luca & Marcellino Monda

  2. Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy

    Davide Viggiano

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  1. Emanuela Viggiano
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  2. Davide Viggiano
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  3. Alessandro Viggiano
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  4. Bruno De Luca
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  5. Marcellino Monda
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Correspondence to Emanuela Viggiano.

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Viggiano, E., Viggiano, D., Viggiano, A. et al. Cortical Spreading Depression Increases the Phosphorylation of AMP-Activated Protein Kinase in the Cerebral Cortex. Neurochem Res 39, 2431–2439 (2014). https://doi.org/10.1007/s11064-014-1447-3

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  • DOI: https://doi.org/10.1007/s11064-014-1447-3

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