Morphometry of the human substantia nigra in ageing and Parkinson’s disease |
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Authors: | 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 |
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Institution: | (1) Neuropathology, Johns Hopkins School of Medicine, Ross Research Building 555, 720 Rutland Avenue, Baltimore, MD 21205, USA;(2) Department of Neurology, Johns Hopkins Bayview Medical Center, B Building, Room 123, 4940 Eastern Avenue, Baltimore, MD 21224, USA;(3) Neuropathology, Johns Hopkins School of Medicine, Ross Research Building 558, 720 Rutland Avenue, Baltimore, MD 21205, USA;(4) Laboratory of Personality and Cognition, Triad Technology Center, 4th Floor, 333 Cassell Drive, Baltimore, MD 21224-6825, USA;(5) The Johns Hopkins Hospital, Phipps 300, 600 N. Wolfe Street, Baltimore, MD 21287, USA;(6) The Johns Hopkins Hospital, The Institute for Cell Engineering, 733 North Broadway, Suite 731, Baltimore, MD 21205, USA;(7) Department of Neurobiology, University of Aarhus, Building 1234 University Park, 8000 Aarhus, Denmark |
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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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Keywords: | Stereology Neuronal volume Alpha-synuclein Neurodegenerative Tyrosine hydroxylase |
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