Acta Neuropathologica

, 115:461

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

  • Gay Rudow
  • Richard O’Brien
  • Alena V. Savonenko
  • Susan M. Resnick
  • Alan B. Zonderman
  • Olga Pletnikova
  • Laura Marsh
  • Ted M. Dawson
  • Barbara J. Crain
  • Mark J. West
  • Juan C. Troncoso
Original Paper

DOI: 10.1007/s00401-008-0352-8

Cite this article as:
Rudow, G., O’Brien, R., Savonenko, A.V. et al. Acta Neuropathol (2008) 115: 461. doi:10.1007/s00401-008-0352-8

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.

Keywords

Stereology Neuronal volume Alpha-synuclein Neurodegenerative Tyrosine hydroxylase 

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Gay Rudow
    • 1
  • Richard O’Brien
    • 2
  • Alena V. Savonenko
    • 3
  • Susan M. Resnick
    • 4
  • Alan B. Zonderman
    • 4
  • Olga Pletnikova
    • 1
  • Laura Marsh
    • 5
  • Ted M. Dawson
    • 6
  • Barbara J. Crain
    • 1
  • Mark J. West
    • 7
  • Juan C. Troncoso
    • 1
  1. 1.NeuropathologyJohns Hopkins School of MedicineBaltimoreUSA
  2. 2.Department of NeurologyJohns Hopkins Bayview Medical CenterBaltimoreUSA
  3. 3.NeuropathologyJohns Hopkins School of MedicineBaltimoreUSA
  4. 4.Laboratory of Personality and CognitionTriad Technology CenterBaltimoreUSA
  5. 5.The Johns Hopkins HospitalBaltimoreUSA
  6. 6.The Johns Hopkins Hospital, The Institute for Cell EngineeringBaltimoreUSA
  7. 7.Department of NeurobiologyUniversity of AarhusAarhusDenmark