Structural study of Purkinje cell axonal torpedoes in essential tremor

Neurosci Lett. 2009 Feb 6;450(3):287-91. doi: 10.1016/j.neulet.2008.11.043. Epub 2008 Nov 24.

Abstract

Essential tremor (ET) is one of the most common neurological diseases. A basic understanding of its neuropathology is now emerging. Aside from Purkinje cell loss, a prominent finding is an abundance of torpedoes (rounded swellings of Purkinje cell axons). Such swellings often result from the mis-accumulation of cell constituents. Identifying the basic nature of these accumulations is an important step in understanding the underlying disease process. Torpedoes, only recently identified in ET, have not yet been characterized ultrastructurally. Light and electron microscopy were used to characterize the structural constituents of torpedoes in ET. Formalin-fixed cerebellar cortical tissue from four prospectively collected ET brains was sectioned and immunostained with a monoclonal phosphorylated neurofilament antibody (SMI-31, Covance, Emeryville, CA). Using additional sections from three ET brains, torpedoes were assessed using electron microscopy. Immunoreactivity for phosphorylated neurofilament protein revealed clear labeling of torpedoes in each case. Torpedoes were strongly immunoreactive; in many instances, two or more torpedoes were noted in close proximity to one another. On electron microscopy, torpedoes were packed with randomly arranged 10-12nm neurofilaments. Mitochondria and smooth endoplasmic reticulum were abundant as well, particularly at the periphery of the torpedo. We demonstrated that the torpedoes in ET represent the mis-accumulation of disorganized neurofilaments and other organelles. It is not known where in the pathogenic cascade these accumulations occur (i.e., whether these accumulations are the primary event or a secondary/downstream event) and this deserves further study.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Axons / pathology*
  • Cerebellar Cortex / pathology*
  • Cerebellar Cortex / physiopathology
  • Endoplasmic Reticulum, Smooth / pathology
  • Essential Tremor / pathology*
  • Essential Tremor / physiopathology
  • Female
  • Humans
  • Microscopy, Electron
  • Microscopy, Immunoelectron
  • Mitochondria / pathology
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Neurofilament Proteins / metabolism
  • Purkinje Cells / pathology*
  • Wallerian Degeneration / pathology
  • Wallerian Degeneration / physiopathology

Substances

  • Neurofilament Proteins