Quantitating silver-stained neurodegeneration: the neurotoxicity of trimethlytin (TMT) in aged rats

• Published in: Journal of neuroscience methods 2000-05, Vol.98 (1), p.69-76
• Main Authors: Scallet, Andrew C, Pothuluri, Nomita, Rountree, Robert L, Matthews, John C
• Format: Article
• Language: English
• Subjects: Aging; Aging - pathology; Animals; Biological and medical sciences; Cell Count; Fink–Heimer; Fundamental and applied biological sciences. Psychology; General aspects. Models. Methods; Hippocampus; Hippocampus - pathology; Image analysis; Image Cytometry; Male; Nerve Degeneration - pathology; Neurodegeneration; Rats; Rats, Inbred F344; Silver Staining - methods; Trimethyltin; Trimethyltin Compounds - toxicity; Vertebrates: nervous system and sense organs
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/S0165-0270(00)00191-6

This report describes the development of a histoanalytical procedure to measure the degree of neurodegeneration produced by the organometal toxicant trimethyltin (TMT). Based on a previous, non-quantitated experiment we hypothesized that the same dose of TMT would produce greater damage in animals of increasing age. Male rats aged 6, 12, 18, or 24 months at the time of dosing were given either 4.5 mg/kg TMT or saline (i.p.). One month after dosing, rats were perfused and their brains removed and processed to selectively silver-impregnate degenerating cell bodies as well as axon terminals and dendrites. Neurodegeneration was most prominent in the hippocampi (especially CA1 stratum radiatum) of TMT-treated rats, but not in the controls. Computer-assisted counting of the silver grains marking damage indicated greater neurotoxicity from the same dose of TMT when given to the older animals. Thus the grain density in the 6-month-old TMT-treated rats was not significantly elevated from the 6-month-old controls ( P>0.10). The 12-month-old TMT-treated rats had significantly increased grain densities compared to their controls ( P