Cholinergic function in lumbar aluminum myelopathy

Kenneth S. Kosik, Walter G. Bradley, Paul F. Good, Chaudri G. Rasool, Dennis J. Selkoe

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

To determine whether perikaryal neurofilamentous accumulation in cholinergic neurons is associated with a deficit in cholinergic function, the authors developed a new model of aluminum-induced neurofibrillary degeneration, referred to as focal lumbar aluminum myelopathy. The model is produced by direct intramedullary microinjection of AlCl3, which results in a characteristic neurological syndrome. Four weeks after injections, affected rabbits show extensive neurofilamentous lesions of both large and small neurons in the lumbar spinal cord, including a majority of anterior horn cells. These animals are capable of long-term survival. Posterior tibial nerve morphometry in these rabbits revealed no significant loss of myelinated fibers. Choline acetyltransferase (ChAT) activity in the sciatic nerve was decreased 39%, from 45.70 ± 2.36 nmol ACh/hour/3-mm segment in acid-injected controls to 17.72 ± 1.94 in aluminum-intoxicated rabbits. The rate of accumulation of ChAT activity proximal to a sciatic nerve ligature was significantly greater in the aluminum-treated rabbits, although the total amount of ChAT activity accumulating in a 24-hour period did not differ from controls. It is concluded that aluminum-induced accumulation of neurofilaments in cholinergic perikarya is associated with a sharp decrease of ChAT activity in the axons of those cells and possibly with a compensatory increase in the rate of delivery of the enzyme.

Original languageEnglish (US)
Pages (from-to)365-375
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume42
Issue number4
DOIs
StatePublished - Jul 1983
Externally publishedYes

Keywords

  • Aluminum
  • Alzheimer’s disease
  • Axonal transport
  • Choline acetyltransferase
  • Cholinergic function
  • Neurofibrillary degeneration
  • Neurofilaments

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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