Differential expression and distribution of α-, β-, and γ-synuclein in the developing human substantia nigra

James E. Galvin, Theresa M. Schuck, Virginia M.Y. Lee, John Q. Trojanowski

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Although the functions of α-, β-, and γ-synuclein (αS, βS, γS, respectively) are unknown, these synaptic proteins are implicated in the pathogenesis of Parkinson's disease (PD) and related disorders. For example, αS forms Lewy bodies (LBs) in substantia nigra (SN) neurons of PD. However, since it is not known how these hallmark PD lesions contribute to the degeneration of SN neurons or what the normal function of αS is in SN neurons, we studied the developing human SN from 11 weeks gestational age (GA) to 16 years of age using immunohistochemistry and antibodies to αS, βS, γS, other synaptic proteins, and tyrosine hydoxylase (TH). SN neurons expressed TH at 11 weeks GA and αS, βS, and γS appeared initially at 15, 17, and 18 weeks GA, respectively. These synucleins first appeared in perikarya of SN neurons after synaptophysin, but about the same time as synaptotagmin and synaptobrevin. Redistribution of αS from perikarya to processes of SN neurons occurred by 18 weeks GA in parallel with synaptophysin, while βS and synaptotagmin were redistributed similarly between 20 and 28 weeks GA and this also occurred with γS and synaptobrevin between 33 weeks GA and 9 months postnatal. These data suggest that αS, βS, and γS may play a functional role in the development and maturation of SN neurons, but it remains to be determined how sequestration of αS as LBs in PD contributes to the degeneration of SN neurons.

Original languageEnglish (US)
Pages (from-to)347-355
Number of pages9
JournalExperimental neurology
Volume168
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Lewy bodies
  • Neurodegeneration
  • Parkinson's disease
  • Substantia nigra
  • Synaptic proteins
  • Synuclein

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Fingerprint

Dive into the research topics of 'Differential expression and distribution of α-, β-, and γ-synuclein in the developing human substantia nigra'. Together they form a unique fingerprint.

Cite this