Age-related accumulation of Marinesco bodies and lipofuscin in rhesus monkey midbrain dopamine neurons: Relevance to selective neuronal vulnerability

Nicholas M. Kanaan, Jeffrey H. Kordower, Timothy J. Collier

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopamine (DA) neurons. Although aging is a primary risk factor for PD, its role in DA neuron degeneration remains unknown. Neurodegeneration in PD is not uniform throughout the ventral midbrain: the ventral tier of the substantia nigra (vtSN) is most vulnerable, whereas the dorsal tier (dtSN) and ventral tegmental area (VTA) are relatively resistant. We studied young (9-10 years old), middle-aged (14-17 years old), and old-aged (22-29 years old) rhesus monkeys to identify factors potentially underlying selective vulnerability and their association with aging. We focused on markers relevant to the ubiquitin-proteasome (UPS) and lysosome systems. Unbiased stereological counting was performed on tyrosine hydroxylase-positive (TH+) neurons and TH+ neurons containing Marinesco bodies (TH+MB) or lipofuscin (TH+lipo), markers of UPS or lysosomal activity, respectively. TH+ neuron numbers were inversely correlated with advancing age specifically in the vtSN, not the dtSN or VTA. TH intensity decreased throughout the ventral midbrain with increasing age, an effect exacerbated in the vtSN. TH+MB neurons were localized in the vulnerable vtSN of old monkeys. The number of MBs per cell increased with age, and TH intensity of TH+MB neurons decreased in middle age. Conversely, TH+lipo neurons were primarily found in the resistant dtSN and VTA. These data suggest that particular age-related changes localize to DAergic subregions relevant to degenerative patterns in PD. Furthermore, the results begin to characterize the nature of the link between aging and PD, and they support the concept that aged monkeys represent a valuable model for studying specific events preceding PD.

Original languageEnglish (US)
Pages (from-to)683-700
Number of pages18
JournalJournal of Comparative Neurology
Volume502
Issue number5
DOIs
StatePublished - Jun 10 2007
Externally publishedYes

Keywords

  • Aging
  • Dopamine neurons
  • Lysosome system
  • Parkinson's disease
  • Primate
  • Ubiquitin proteasome system

ASJC Scopus subject areas

  • Neuroscience(all)

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