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Expression of alpha-synuclein in non-apoptotic, slowly degenerating facial motoneurones

  • Published:
Journal of Neurocytology

Abstract

The discovery that missense mutations in the alpha-synuclein gene represent a rare genetic cause of Parkinson's disease (PD) has had significant impact on the development of research into neurodegenerative disorders. It is becoming increasingly clear that alpha-synuclein plays a central role in the pathological process, which causes Lewy body formation and neurodegeneration in PD. Importantly, there is evidence to suggest that mutated alpha-synuclein is toxic to both nerve cells and glia. However, the regulation and function of wild-type alpha-synuclein are as yet ill defined. Using the facial nerve axotomy model, we have addressed the question whether the expression of alpha-synuclein in nerve cells may change in response to injury. We were particularly interested in testing the hypothesis that the severity of neuronal injury had an effect on alpha-synuclein metabolism. Facial nerve cut and crush, respectively, were performed in adult rats where normal facial motoneurones do not express alpha-synuclein. Following axotomy, a subset of facial motoneurones newly expressed high levels of alpha-synuclein immunoreactivity in their cell body and, occasionally, their nucleus. Significantly more nerve cells were labelled following facial nerve transection than following facial nerve crush. Confocal microscopy revealed a granular pattern of alpha-synuclein aggregation in degenerating nerve cells. Interestingly, the observed cell death phenotype was clearly non-apoptotic and developed over days or weeks rather than hours. Thus, axotomy of adult rat facial motoneurones triggers de novo expression of alpha-synuclein and this expression is associated with a non-apoptotic, slow form a neurodegeneration. In addition, the extent of alpha-synuclein expression is related to the severity of neuronal injury.

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Authors and Affiliations

  1. Department of Neuropathology, Faculty of Medicine, Imperial College, London, UK

    L. B. Moran, S. Kösel & M. B. Graeber

  2. Department of Neurology, RWTH Aachen, Aachen, Germany

    C. Spitzer

  3. Aurigon Life Science GmbH, Tutzing, Germany

    F. W. Schwaiger

  4. Department of Medical Genetics, University of Tübingen, Tübingen, Germany

    O. Riess

  5. Department of Neuromorphology, Max-Planck-Institute of Neurobiology, Martinsried, Germany

    G. W. Kreutzberg

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  1. L. B. Moran
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  2. S. Kösel
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  3. C. Spitzer
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  4. F. W. Schwaiger
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  5. O. Riess
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  6. G. W. Kreutzberg
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  7. M. B. Graeber
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Correspondence to M. B. Graeber.

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Moran, L.B., Kösel, S., Spitzer, C. et al. Expression of alpha-synuclein in non-apoptotic, slowly degenerating facial motoneurones. J Neurocytol 30, 515–521 (2001). https://doi.org/10.1023/A:1015697318437

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