Neurofilament mRNA is reduced in Parkinson's disease substantia nigra pars compacta neurons

William D Hill, Motomi Arai, Jeffrey A. Cohen, John Q. Trojanowski

Research output: Contribution to journalArticle

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Abstract

Lewy bodies are filamentous neuronal inclusions characteristic of Parkinson's disease, and neurofilament triplet proteins are the major components of the filaments in Lewy bodies. Since the neurofilament proteins found in Lewy bodies are abnormally phosphorylated and partially degraded, the formation of Lewy bodies may be due to the defective metabolism of these proteins, and this could lead to impairments in the structure and function of neurofilament rich neuronal processes (i.e., large caliber axons). To gain further insights into the metabolism of neurofilaments in Parkinson's disease, we evaluated neurofilament mRNA levels by semiquantitative in situ hybridization histochemistry in postmorten tissues from Parkinson's disease and control subjects. Substantia nigra pars compacta neurons were examined with digoxigenin‐UTP labeled cRNA probes to the heavy and light neurofilament mRNAs. The relative abundance of these mRNAs was measured by videodensitometric image analysis of chromogenic reaction product. Using this approach, we demonstrated that the levels of both heavy and light neurofilament mRNAs were reduced in Parkinson's disease substantia nigra pars compacta neurons. Additionally, the levels of heavy neurofilament mRNA were lowest in Lewy body containing neurons in the Parkinson's disease cases. These results suggest that the formation of neurofilament‐rich Lewy bodies in substantia nigra pars compacta neurons is associated with reduced levels of the heavy and light neurofilament mRNAs in Parkinson's disease. Thus, it is possible that the accumulation of abnormal neurofilament proteins in Lewy bodies and diminished neurofilament mRNAs contribute to the degeneration of substantia nigra pars compacta neurons in Parkinson's disease. © 1993 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)328-336
Number of pages9
JournalJournal of Comparative Neurology
Volume329
Issue number3
DOIs
Publication statusPublished - Jan 1 1993

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Keywords

  • Lewy body
  • cRNA
  • in situ hybridization
  • non‐radioactive

ASJC Scopus subject areas

  • Neuroscience(all)

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