IDPN Rat Model -- Helen Wang, Ph.D.
Immunohistochemistry of advanced glycation end-products
in neurofilamentous axonal spheroids induced by IDPN
in lower motor neurons of rat.
Wang H, Taniguchi A and Chou S.
J Neurol Sci 177, (2), 139-145, September, 2000
Chronic parenteral administration of beta-beta'-iminodipropionitrile (IDPN) in adult
female rats induces large neurofilament-rich axonal spheroids (AXS) in spinal
motor neurons closely resembling those AXS in early phases of amyotrophic lateral sclerosis.
Immunohistochemistry of advanced glycosylation end-products (AGEs) in axonal spheroids was
performed in the present study. Anti-AGE and anti-neurofilament antibodies strongly
co-labeled IDPN-induced axonal spheroids, whereas motor neuron soma showed little
AGE immunoreactivity. In an attempt to modify and intensify glycosylation,
another group of IDPN rats was made hyperglycemic with streptozotocin after IDPN intoxication.
These hyperglycemic rats showed AXS with striking AGE immunoreactivity.
An additional group of rats made hyperglycemic before IDPN intoxication showed markedly
diminished AXS formation, with a few small AGE-positive AXS in anterior horns.
Findings suggest that AGEs are involved in neurofilament crosslinking as well as
disassembly of neurofilament induced by IDPN with or without hyperglycemia.
Hyperglycemia did not intensify neurofilament aggregation. Additional immunohistochemistry
revealed not only aberrant phosphorylation, but also intense local production of
Cu/Zn superoxide dismutase and nitrotyrosine in axonal spheroids,
probably secondary to superoxide generation as a consequence of AGE production
at neurofilament protein, impeding its assembly as hypothesized in motoneuron diseases.
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