Preservation of midbrain catecholaminergic neurons in very old human subjects

Abstract

Parkinson's disease is characterized by a progressive degeneration of dopaminergic neurons in the midbrain, yet the cause of this neuronal loss is still unknown. It has been hypothesized that Parkinson's disease could be the consequence of accelerated ageing. In order to reveal a possible common process during ageing and Parkinson's disease neurodegeneration, catecholaminergic neurons of five anatomical regions of the brainstem (substantia nigra, central grey substance, ventral tegmental area, peri- and retrorubral area, and locus coeruleus) have been quantified using immunohistochemical staining for tyrosine hydroxylase (TH) on regularly spaced sections, between the rostral and caudal poles of the mesencephalon and in the rostral pole of the pons, in post-mortem samples of 21 control subjects who died at ages 44-110 years. No statistically significant loss of TH positive neurons was observed in the older subjects, either in the substantia nigra or in the other midbrain regions that are known to degenerate to a lesser degree in Parkinson's disease. Furthermore, in the later regions no neuronal loss was observed from age 44 to 80 years, indicating that this result is not dependent on the inclusion of 'supernormal' very old people. These results suggest that from age 44 to 110 years, ageing in control adults is not, or is scarcely, accompanied by catecholaminergic cell loss in the midbrain and hence Parkinson's disease is probably not caused by an acceleration of a degenerative process during ageing.

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

“…A previous morphological study of the TH (+) neurons in the human SN found no correlation of cell body size with age [27]. Although stereological studies of the SN have not examined the volume of TH (+) neurons in normal ageing, there is evidence for a close correspondence between pigmented and TH (+) neurons [2,7].…”

“…Kubis et al [27] did not find a significant loss of TH (+) in the SN, nor in other midbrain regions, in a series of 21 control subjects who died at ages 44-110. In contrast, we have shown a 36% (P < 0.001) loss of TH (+) SN neurons in older controls compared to younger subjects.…”

Interactions Between Environmental and Genetic Factors in the Pathophysiology of Parkinson's Disease

“…Hence oxidative stress produced during PD is likely the consequence of H 2 O 2 production due to a combination of dopamine oxidation, GSH depletion and Fe 2+ generated from neuromelanin, thus allowing Fenton reaction to proceed at a considerable rate leading to neuronal death. This hypothesis gains support from the observation that neuromelanincontaining neurons are preferentially lost during the course of PD (31). It remains to be elucidated whether iron accumulation precedes injury of pigmented neurons or occurs as a consequence of neuronal degeneration.…”

Aging and Sedentarism Decrease Vascularization and VEGF Levels in the Rat Substantia Nigra. Implications for Parkinson's Disease

“…Perfusion deficits have also been observed before the onset of clinical symptoms in other neurodegenerative disorders, which suggests that the deficits contribute to the pathogenesis of the disease (Storkebaum and Carmeliet, 2004). Conflicting results have been obtained in different studies, with either an age-dependent depletion or no change in DA neuron counts, which may be attributable to a number of methodological variables (Kubis et al, 2000;Collier et al, 2007). However, the present results support observations of a progressive functional decline in the SNc and increased vulnerability to injury with age.…”