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 = grudow1@jhmi.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 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.

Neuromelanin Magnetic Resonance Imaging in Parkinson's Disease and Multiple System Atrophy

“…Our results are in agreement with those of Sasaki et al [15]. Additionally, we showed that the contrast ratio of the SNc was correlated with the Hoehn-Yahr stage of PD, which is in accordance with progressive neuromelanin loss during the course of the disease [25]. Consequently, this method is a potential biomarker for neurodegeneration in the SNc and LC of PD patients.…”

Parkinson disease and incidental Lewy body disease

“…As for the mean age at death, PD and ILBD did not differ with respect to C, while PD differed vs ILBD, with the ILBD group being older. These findings substantiated the comparability of the mean age at death between ILBD and C, and reduced possible confounding effects due to aging 31 on the NNL measured in ILBD. No differences were observed for the mean PMI and BW across all 3 groups.…”

RTP801 Is Induced in Parkinson's Disease and Mediates Neuron Death by Inhibiting Akt Phosphorylation/Activation

“…For instance, mTOR and Akt regulate cell mass and Akt has trophic actions on neurons including increasing their size and degree of sprouting (Ries et al, 2006) as well as the caliber and branching of axons (Markus et al, 2002). In PD, in contrast, there is a significant atrophy of pigmented SN neurons (Rudow et al, 2008). mTOR (Swiech et al, 2008) and Akt (Jaworski et al, 2005;Kumar et al, 2005) signaling pathways also play critical roles in dendritic arborization which is markedly reduced in neurons affected by PD (Patt and Gerhard, 1993;Kumar et al, 2005).…”