Journal of Neuroscience, Vol 4, 722-731, Copyright © 1984 by Society for Neuroscience
Aluminum effect on slow axonal transport: a novel impairment of neurofilament transport
A Bizzi, RC Crane, L Autilio-Gambetti and P Gambetti
Administration of aluminum (Al) produces accumulation of neurofilaments
(NF), called neurofibrillary tangles (NFT), in neuronal cell bodies and
proximal axonal segments. This study was undertaken to investigate whether
these changes are associated with impairment of the slow axonal transport.
Local administration of AlCl3 induced the formation of NFT in 90 to 100% of
the rabbit hypoglossal neurons. [35S]Methionine was then administered to
the hypoglossal nerve nuclei. The hypoglossal nerves were processed 18 or
28 days later for one- and two-dimensional SDS-polyacrylamide gel
electrophoresis and fluorography. Labeled NF polypeptides and a polypeptide
of 57 kilodaltons (Kd) were not detectable beyond the proximal 9-mm segment
of the hypoglossal nerve in Al-treated rabbits 18 days after labeling,
whereas they were present up to 27 mm from the medulla in controls. Tubulin
and polypeptides migrating with slow component b were not significantly
affected. In rabbits sacrificed 28 days after labeling, accumulation of NF
subunits within the proximal 9 mm of hypoglossal nerve was less dramatic,
and labeled NF were present up to 30 mm from the medulla whereas they were
detectable up to 45 mm in controls. Morphological studies demonstrated the
presence of enlarged axons filled with NF in the proximal 9 mm of the
hypoglossal nerve. In nerve segments immediately distal, axons were
markedly reduced in size and contained no NF but an apparently normal
number of microtubules and other organelles. Transport of NF and of a 57-Kd
polypeptide is markedly but reversibly slowed down or blocked within the
proximal 9-mm segments of the hypoglossal nerve following Al administration
to the hypoglossal nucleus. It is suggested that NF transport is maintained
distally, resulting in lack of NF in axonal segments immediately distal to
the block. Local Al intoxication provides a novel model of impairment of NF
transport.
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