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Differential Changes in Phosphorylation of Tau at PHF-1 and 12E8 Epitopes During Brain Ischemia and Reperfusion in Gerbils

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Abstract

Cortical neurons are vulnerable to ischemic insult, which may cause cytoskeletal changes and neurodegeneration. Tau is a microtubule-associated protein expressed in neuronal and glial cells. We examined the phosphorylation status of tau protein in the gerbil brain cortex during 5 min ischemia induced by bilateral common carotid artery occlusion followed by reperfusion for 20 min to 7 days. Control brain homogenates contained 63, 65 and 68 kD polypeptides of tau immunoreactive with Alz 50, Tau 14 and Tau 46 antibodies raised against non-phosphorylated tau epitopes. Gerbil tau was also immunoreactive with some (PHF-1 and 12E8) but not all (AT8, AT100, AT180 and AT270) antibodies raised against phosphorylated tau epitopes. PHF-1 recognized a single 68 kD polypeptide and 12E8 bound the 63 kD polypeptide. During 5 min ischemia, PHF-1 immunoreactivity declined to 6%, then recovered to control levels after 20 min of blood recirculation and subsequently increased above control values 3 and 7 days later. In contrast, 12E8 immunoreactivity remained stable during ischemia and reperfusion. Our results suggest that the two phosphorylated epitopes of tau are regulated by different mechanisms and may play different roles in microtubule dynamics. They may also define various pools of neuronal/glial cells vulnerable to ischemia.

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Acknowledgments

The authors express special thanks to Drs. Peter Davies and Bridget Shafit-Zagardo (Albert Einstein College of Medicine, Bronx, NY), Peter Seubert (Athena Neurosciences, Inc. and Elan Pharmaceuticals, Inc., CA), David Martin (Genentech Inc, San Francisco, CA), André Delacourte and Luc Buée (INSERM U422, Lille Cedex, France), Lester Binder (Northwestern University, IL) and A. Van de Voorde and E. Vanmechelen of Innogenetics, N.V. (Ghent, Belgium) for generous gifts of antibodies. The authors gratefully acknowledge an expert technical assistance of Mrs. Apolonia Ziembowicz.

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Authors and Affiliations

  1. Neuroinflammation Research Laboratories, Dept. Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1230, New York, NY, 10029, USA

    H. Ksiezak-Reding

  2. Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA

    W. Gordon-Krajcer & H. Ksiezak-Reding

  3. Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

    W. Gordon-Krajcer, E. Kozniewska & J. W. Lazarewicz

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  1. W. Gordon-Krajcer
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  2. E. Kozniewska
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  3. J. W. Lazarewicz
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  4. H. Ksiezak-Reding
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Correspondence to H. Ksiezak-Reding.

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Special issue dedicated to John P. Blass.

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Gordon-Krajcer, W., Kozniewska, E., Lazarewicz, J.W. et al. Differential Changes in Phosphorylation of Tau at PHF-1 and 12E8 Epitopes During Brain Ischemia and Reperfusion in Gerbils. Neurochem Res 32, 729–737 (2007). https://doi.org/10.1007/s11064-006-9199-3

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