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Correlation between Bax overexpression and prion deposition in medulla oblongata from natural scrapie without evidence of apoptosis

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Abstract

Although apoptosis has been implicated in the neuronal loss observed in prion diseases, the participation of apoptosis-related factors, like the Bcl-2 family of proteins, is still not clear. Moreover, there are conflicting data concerning the major role of apoptosis in the neuropathology associated with transmissible spongiform encephalopathies. Many studies have been developed in vitro or in experimentally infected animal models but, at present, little is known about this process in natural spontaneous and acquired prion diseases. In this work, the implication of Bax and Bcl-2 has been investigated by the analysis of their expression and protein distribution in medulla oblongata of naturally scrapie-infected sheep. Moreover, their spatial relationship with PrPSc deposition, neuronal vacuolation and neuropil spongiosis has also been analysed as well as the possible induction of neuronal apoptosis in this model. Real Time RT-PCR showed overexpression of the pro-apoptotic gene Bax in scrapie medullas, and immunohistochemistry confirmed its accumulation. No variation of Bcl-2 was observed at the level of gene expression or protein production. Bax distribution, PrPSc deposition, neuronal vacuolation and spongiosis were quantified in different medulla oblongata nuclei and their spatial relationship was evaluated. Bax staining showed a positive correlation with prion deposition, suggesting that this factor is involved in prion neurotoxicity in our natural model. Despite Bax overexpression, neuronal apoptosis was revealed neither by TUNEL nor by immunohistochemical detection of the activated form of caspase-3. This lack of apoptosis could be attributed to the relatively low number of neurons in this area or to the existence of neuroprotective mechanisms in medulla oblongata motor neurons.

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Acknowledgments

The authors thank Nuria Segovia and Silvia Ruiz for their technical assistance. This work was performed as part of the EET2003-09890 project (CICYT/FEDER), Red CIEN (Carlos III Institute), Fondo de Investigación Sanitaria (PI020840) and Research Consolidated Groups from the Aragon Government. J. Lyahyai and C. Serrano were supported by AECI (MAE) and DGA doctoral grants, respectively, and I. Martín-Burriel by a research contract from the Ramón y Cajal Program.

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Authors and Affiliations

  1. Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet 177, 50013, Zaragoza, Spain

    Jaber Lyahyai, Carmen Serrano, Rosario Osta, Pilar Zaragoza & Inmaculada Martín-Burriel

  2. Centro Nacional de Referencia de EETs, Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet 177, 50013, Zaragoza, Spain

    Rosa Bolea, Eva Monleón, Juan J. Badiola & Inmaculada Martín-Burriel

  3. Mejora Animal, Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet 177, 50013, Zaragoza, Spain

    Carlos Moreno

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  1. Jaber Lyahyai
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Correspondence to Inmaculada Martín-Burriel.

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Lyahyai, J., Bolea, R., Serrano, C. et al. Correlation between Bax overexpression and prion deposition in medulla oblongata from natural scrapie without evidence of apoptosis. Acta Neuropathol 112, 451–460 (2006). https://doi.org/10.1007/s00401-006-0094-4

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  • DOI: https://doi.org/10.1007/s00401-006-0094-4

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