Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice

Hum Mol Genet. 1999 Jul;8(7):1227-36. doi: 10.1093/hmg/8.7.1227.

Abstract

How aggregates of polyglutamine proteins are involved in the neurological symptoms of glutamine repeat diseases is unknown. We show that huntingtin aggregates are present in the neuronal processes of transgenic mice that express exon 1 of the Huntington's disease (HD) gene. Unlike aggregates in the nucleus, these neuropil aggregates are usually smaller and are not ubiquitinated. Electron microscopy reveals many neuropil aggregates in axons and axon terminals. Huntingtin aggregates in the axon terminal are co-localized with some synaptic vesicles, implying that they may affect synaptic transmission and neuronal communication. The formation of neuropil aggregates is highly correlated with the development of neurological symptoms. The present study raises the possibility that neuropil aggregates may cause a dysfunction in neuronal communication and con-tribute to the neurological symptoms of HD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Disease Progression
  • Exons
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics
  • Huntington Disease / pathology*
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism*
  • Neuropil / metabolism*
  • Neuropil / ultrastructure
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology
  • Nuclear Proteins / metabolism*
  • Ubiquitins / metabolism

Substances

  • Antibodies
  • HTT protein, human
  • Htt protein, mouse
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Ubiquitins