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Increased expression of water channel aquaporin 1 and aquaporin 4 in Creutzfeldt-Jakob disease and in bovine spongiform encephalopathy-infected bovine-PrP transgenic mice

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Abstract

Spongiform change is a cardinal feature in transmissible spongiform encephalopathies, including Creutzfeldt-Jakob disease (CJD) and bovine spongiform encephalopathy (BSE). It is characterized by swelling of the neuronal processes and vacuolization of the neuropil, leading to increased intraneuronal water content. The present study examines, by gel electrophoresis and Western blotting, the expression levels of the water channels aquaporin 1 (AQP1) and aquaporin 4 (AQP4) in the frontal cortex (area 8) homogenates of sporadic CJD cases (six men, four women; seven cases with methionine/methionine at codon 129 and PrP type 1; two cases with valine/valine at codon 129 and PrP type 2, and one case methionine/valine at codon 129 and PrP type 1) compared with age-matched controls, and cases with Alzheimer’s disease (AD, stage VI of Braak and Braak) and diffuse Lewy body disease (DLB). AQP1 and AQP4 protein levels were also studied in the cerebral cortex of BSE-infected bovine-PrP transgenic mice (BoPrP-Tg110 mice) examined at 60, 150, 210 and 270 days post-inoculation (dpi) compared with healthy brain-inoculated control mice. Quantitative densitometry of AQP bands normalized for β-actin was analyzed using Statgraphics plus 5.0 software from ANOVA and LSD statistical tests. Significant increased expression levels of AQP1 (as revealed with two different antibodies) and AQP4 were seen in CJD, but not in advanced AD and DLB cases when compared with controls. Immunohistochemistry revealed that AQP1 and AQP4 were expressed in astrocytes in diseased cases. No modifications in the expression levels of AQP1 and AQP4 were observed in BSE-infected bovine-PrP transgenic mice at 60, 150 and 210 dpi. However, a significant increase in the expression levels of AQP1 and AQP4 was found in mice at 270 dpi, the time corresponding with the appearance of PrPres immunoreactivity in Western blots and typical spongiform lesions in the brain. Together, these findings show increased expression of water channels in the brain in human and animal prion diseases. These modifications may have implications in the regulation of water transport in astrocytes and may account for an imbalance in water and ion homeostasis in prion diseases.

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Acknowledgments

This work was supported in part by the Ministerio de Ciencia y Tecnología: EET 2001-3724 and EET2002-05168, and CAL01-018 NoE Neuroprion CT-2004-506579. We wish to thank T. Yohannan for editorial assistance.

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  1. Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Universitat de Barcelona, carrer Feixa Llarga sn, 08907 Hospitalet de Llobregat, Barcelona, Spain

    Agustín Rodríguez, Esther Pérez-Gracia & Isidro Ferrer

  2. Centro de Investigación en Sanidad Animal (CISA), INIA, Valdeolomos, 28130, Madrid, Spain

    Juan Carlos Espinosa & Juan María Torres

  3. Departament de Medicina Animal i Cirurgia, Facultat de Veterinaria, Universitat Autonoma de Barcelona, Bellaterra, Spain

    Martí Pumarola

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  1. Agustín Rodríguez
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Correspondence to Isidro Ferrer.

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Rodríguez, A., Pérez-Gracia, E., Espinosa, J.C. et al. Increased expression of water channel aquaporin 1 and aquaporin 4 in Creutzfeldt-Jakob disease and in bovine spongiform encephalopathy-infected bovine-PrP transgenic mice. Acta Neuropathol 112, 573–585 (2006). https://doi.org/10.1007/s00401-006-0117-1

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  • DOI: https://doi.org/10.1007/s00401-006-0117-1

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