Neuronal cytoskeletal lesions induced in the CNS by intraventricular and intravenous aluminium maltol in rabbits

Abstract

The antigenicity of neuronal cytoskeletal lesions was studied immunohistochemically in adult New Zealand white rabbits after intraventricular (subacute) and intravenous (chronic) administration of a water-soluble aluminium compound, aluminium (Al) maltol. After short-term intraventricular administration, rabbits developed widespread neurofibrillary degeneration (NFD) involving pyramidal neurons of the isocortex and allocortex, projection neurons of the diencephalon, and nerve cells of the brain stem and spinal cord. There was a predilection for motor neuron involvement and for the infratentorial portions of the neuraxis. Perikarya and proximal neurites were especially affected. Bundles of 10 nm filaments were frequently present. Three of the animals treated intravenously for 12 weeks or longer displayed NFD in the oculomotor complex and in the pyramidal neurons of the occipital isocortex. Following either mode of administration, the affected neurons exhibited immunostaining with a panel of monoclonal antibodies (MAbs) against phosphorylated (SMI-31), non-phosphorylated/phosphatase-sensitive (SMI-32), and dephosphorylation-independent (SMI-33) epitopes of high and middle molecular weight neurofilament (NF) protein subunits. They were non-reactive with MAbs to microtubule-associated protein 2 and the class III neuron-associated beta-tubulin isotype. Our findings indicate that intraventricular Al maltol produces similar, but more widespread degeneration of projection-type neurons than the less water-soluble Al compounds as reported by others. The NFD lesions are compared with those of senile dementia of the Alzheimer type (SDAT) and motor neuron disease.

Osmium(II) and Ruthenium(II) Arene Maltolato Complexes: Rapid Hydrolysis and Nucleobase Binding

“…[16] GalliumA C H T U N G T R E N N U N G (III) tris(maltolate) is on clinical trial as an anticancer agent, [17] and has potential as a radiopharmaceutical, [18] and ferric tris(maltolate) has been investigated for the treatment of iron-deficiency anaemia. [19,20] Some reactions of Ru II -arene complexes containing maltolate and similar ligands, for example, ethylmaltolate, have been reported, [21][22][23][24] but not those of their Os (2) containing O,O-chelated maltolate, as well as the acidity of their aqua adducts.…”

Neuron-associated class III ?-tubulin, tau, and MAP2 in the D-283 Med cell line and in primary explants of human medulloblastoma

“…Details of the procedures and controls used for immunohistochemical staining for ]3-tubulin isotypes, tau protein, microtubule~associated protein 2 (MAP2), neuron-specific (y7) enolase (NSE), synaptophysin, vimentin and glial fibrillary acidic protein have been previously described (Caccamo el a]., 1989a). Those for neurofilament proteins have also been reported Katsetos et al, 1990), as have the procedures and controls for Leu 7 and retinal S-antigen (Caccamo et al, 1989b).…”

Aluminum inhibits neurofilament protein degradation by multiple cytoskeleton‐associated proteases

“…The environmental neurotoxin aluminum causes disordered whorls of neurofilaments to accumulate in perikarya in situ and in culture [1][2][3][4][5][6][7][8][9]. Since the expression of mRNA coding for neurofilament subunits is reduced during aluminum intoxication [10,11], these studies suggest that aluminum may disrupt postsynthetic events such as neurofilament protein turnover, posttranslational processing and axonal transport.…”