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Increased PKR level in human CADASIL brains

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Abstract

Cerebral autosomal dominant arteriolopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is the most common form of hereditary small vessel disease (SVD) of the brain. Neuronal apoptosis has been demonstrated in the cortex of patients. Whether it is associated with an activation of the pro-apoptotic protein PKR pathway is unknown. Similarly, activation of autophagy in CADASIL has never been explored. Immunostaining of four CADASIL brains previously analyzed for cortical neuronal apoptosis and five control brains for PKR (phosphoPKR) and autophagy (ATG5, LC3II) activation markers. Significant nuclear pPKR staining was observed in CADASIL neurons comparatively to controls (p = 0.001). No difference was observed between patients and controls with autophagy markers. We demonstrated the activation of PKR pathway in CADASIL. This was not associated with a detectable modulation of autophagy. These results open a new field to explore in order to better understand the mechanisms underlying cortical neurons apoptosis.

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Acknowledgments

We thank the patients who were involved in this study. We thank Dr. Marc Polivka and Pr. Françoise Gray who performed the autopsies.

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Authors and Affiliations

  1. INSERM U942, Paris, France

    Emmanuel Cognat, Marion Tible, Ilyes Methnani, Jacques Hugon & Claire Paquet

  2. University of Paris Diderot, Sorbonne Paris Cité, UMRS INSERM U942, Paris, France

    Emmanuel Cognat, Jacques Hugon & Claire Paquet

  3. Cognitive Neurology Center, Lariboisière Fernand-Widal Hospital, APHP, 200 rue du Faubourg Saint Denis, 75475, Paris Cedex, France

    Emmanuel Cognat, Hugues Chabriat, Homa Adle-Biassette, Jacques Hugon & Claire Paquet

  4. Department of Neurology, Lariboisière Fernand-Widal Hospital, APHP, Paris, France

    Hugues Chabriat

  5. Department of Pathology, Lariboisière Fernand-Widal Hospital, APHP, Paris, France

    Homa Adle-Biassette

  6. INSERM U1141, Paris, France

    Homa Adle-Biassette

Authors
  1. Emmanuel Cognat
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  2. Marion Tible
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  3. Ilyes Methnani
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  4. Hugues Chabriat
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  5. Homa Adle-Biassette
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  6. Jacques Hugon
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  7. Claire Paquet
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Contributions

Emmanuel Cognat wrote the manuscript and prepared figures. Marion Tible participated to manuscript writing and analysis of data. Ilyes Methnani and Homa Adle-Biassette contributed to the experimental procedures and Jacques Hugon contributed to the conception of the study. Claire Paquet conceived the study and wrote the manuscript. All authors proofread the manuscript.

Corresponding author

Correspondence to Claire Paquet.

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Cognat, E., Tible, M., Methnani, I. et al. Increased PKR level in human CADASIL brains. Virchows Arch 473, 771–774 (2018). https://doi.org/10.1007/s00428-018-2425-y

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  • DOI: https://doi.org/10.1007/s00428-018-2425-y

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