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Parkinson’s disease: lesions in dorsal horn layer I, involvement of parasympathetic and sympathetic pre- and postganglionic neurons

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Abstract

Clinical signs frequently recognized in early phases of sporadic Parkinson’s disease (PD) may include autonomic dysfunctions and the experience of pain. Early disease-related lesions that may account for these symptoms are presently unknown or incompletely known. In this study, immunocytochemistry for α-synuclein was used to investigate the first relay stations of the pain system as well as parasympathetic and sympathetic pre- and postganglionic nerve cells in the lower brainstem, spinal cord, and coeliac ganglion in 100 μm polyethylene glycol embedded sections from six autopsy individuals, whose brains were staged for PD-associated synucleinopathy. Immunoreactive inclusions were found for the first time in spinal cord lamina I neurons. Lower portions of the spinal cord downwards of the fourth thoracic segment appeared to be predominantly affected, whereas the spinal trigeminal nucleus was virtually intact. Additional involvement was seen in parasympathetic preganglionic projection neurons of the vagal nerve, in sympathetic preganglionic neurons of the spinal cord, and in postganglionic neurons of the coeliac ganglion. The known interconnectivities between all of these components offer a possible explanation for their particular vulnerability. Lamina I neurons (pain system) directly project upon sympathetic relay centers, and these, in turn, exert influence on the parasympathetic regulation of the enteric nervous system. This constellation indicates that physical contacts between vulnerable regions play a key role in the pathogenesis of PD.

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Acknowledgments

This work was funded by a grant (Br 317/17-3) from the Deutsche Forschungsgemeinschaft (DFG). The contributing authors have no existing or pending conflicts of interest. Autopsies were performed in compliance with the ethics committee guidelines of all three participating institutions. We thank Mr. Mohamed Bouzrou (laboratory technical assistance) and Ms. Inge Szász-Jacobi (graphics) for technical support.

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  1. Institute for Clinical Neuroanatomy, J.W. Goethe University Clinic, Theodor Stern Kai 7, 60590, Frankfurt am Main, Germany

    Heiko Braak, Magdalena Sastre & Kelly Del Tredici

  2. Department of Neuropathology, Johannes Gutenberg University, Langenbeckstrasse 1, Mainz, Germany

    Jürgen R. E. Bohl

  3. Laboratorium Pathologie Oost Nederland, Burg Edo Bergmalaan 1, AD 7512, Enschede, The Netherlands

    Rob A. I. de Vos

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Correspondence to Heiko Braak.

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Braak, H., Sastre, M., Bohl, J.R.E. et al. Parkinson’s disease: lesions in dorsal horn layer I, involvement of parasympathetic and sympathetic pre- and postganglionic neurons. Acta Neuropathol 113, 421–429 (2007). https://doi.org/10.1007/s00401-007-0193-x

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