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Morphometry of the human substantia nigra in ageing and Parkinson’s disease

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Abstract

To investigate the relation between the loss of substantia nigra (SN) neurons in normal ageing and Parkinson’s disease (PD), we measured the total number and the cell body volume of pigmented (neuromelanin) neurons in the SN. We examined young (n = 7, mean age: 19.9), middle-aged (n = 9, mean age: 50.1), and older controls from the Baltimore Longitudinal Study of Aging (n = 7, mean age: 87.6), as well as PD cases (n = 8, mean age: 74.8). On random-systematically selected paraffin Nissl-stained sections, we used the Optical Fractionator to estimate the total number of neurons on one side of the SN. Using the Nucleator probe, we measured the volume of these neurons. In young and older controls, we also estimated the total number and volume of tyrosine hydroxylase (TH) positive (+) nigral neurons. We observed a significant loss of pigmented (-28.3%, P < 0.01) and TH (+) (−36.2%, P < 0.001) neurons in older controls compared with younger subjects. Analysis of the size distribution of pigmented and TH (+) neurons showed a significant hypertrophy in older controls compared to young controls (P < 0.01). In contrast, in PD we observed a significant atrophy of pigmented neurons compared to all control groups (P < 0.01). These data suggest that neuronal hypertrophy represents a compensatory mechanism within individual SN neurons that allows for normal motor function despite the loss of neurons in normal ageing. Presumably, this compensatory mechanism breaks down or is overwhelmed by the pathological events of PD leading to the onset of the characteristic motor disturbances.

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Acknowledgments

We are grateful to the BLSA participants and staff. Ms. Karen Wall is recognized for editorial assistance and Dr. An Yang for his advice on statistics. This work was supported by the Johns Hopkins University Morris K. Udall Parkinson’s Disease Research Center of Excellence (P50 NS38377) and Alzheimer’s Disease Research Center (P50 AG05146) and by the Intramural Research Program of the National Institute on Aging, NIH.

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Authors and Affiliations

  1. Neuropathology, Johns Hopkins School of Medicine, Ross Research Building 555, 720 Rutland Avenue, Baltimore, MD, 21205, USA

    Gay Rudow, Olga Pletnikova, Barbara J. Crain & Juan C. Troncoso

  2. Department of Neurology, Johns Hopkins Bayview Medical Center, B Building, Room 123, 4940 Eastern Avenue, Baltimore, MD, 21224, USA

    Richard O’Brien

  3. Neuropathology, Johns Hopkins School of Medicine, Ross Research Building 558, 720 Rutland Avenue, Baltimore, MD, 21205, USA

    Alena V. Savonenko

  4. Laboratory of Personality and Cognition, Triad Technology Center, 4th Floor, 333 Cassell Drive, Baltimore, MD, 21224-6825, USA

    Susan M. Resnick & Alan B. Zonderman

  5. The Johns Hopkins Hospital, Phipps 300, 600 N. Wolfe Street, Baltimore, MD, 21287, USA

    Laura Marsh

  6. The Johns Hopkins Hospital, The Institute for Cell Engineering, 733 North Broadway, Suite 731, Baltimore, MD, 21205, USA

    Ted M. Dawson

  7. Department of Neurobiology, University of Aarhus, Building 1234 University Park, 8000, Aarhus, Denmark

    Mark J. West

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  1. Gay Rudow
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Correspondence to Gay Rudow.

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Rudow, G., O’Brien, R., Savonenko, A.V. et al. Morphometry of the human substantia nigra in ageing and Parkinson’s disease. Acta Neuropathol 115, 461–470 (2008). https://doi.org/10.1007/s00401-008-0352-8

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  • DOI: https://doi.org/10.1007/s00401-008-0352-8

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