title: Morphometry of the human substantia nigra in ageing and Parkinson's disease.
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.
authors.affiliation: Neuropathology, Johns Hopkins School of Medicine, Ross Research Building 555, 720 Rutland Avenue, Baltimore, MD 21205, USA. grudow1@jhmi.edu
authors.forename: Gay
authors.initials: G
authors.lastname: Rudow
authors.forename: Richard
authors.initials: R
authors.lastname: O'Brien
authors.forename: Alena V
authors.initials: AV
authors.lastname: Savonenko
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zonderman
authors.forename: Olga
authors.initials: O
authors.lastname: Pletnikova
authors.forename: Laura
authors.initials: L
authors.lastname: Marsh
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Crain
authors.forename: Mark J
authors.initials: MJ
authors.lastname: West
authors.forename: Juan C
authors.initials: JC
authors.lastname: Troncoso
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000704:Analysis of Variance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology*; D010300:Parkinson Disease / Q000473:pathology*; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000473:pathology*