Effect of Triethyl Tin on Myelination in the Developing Rat

Abstract

Myelinogenesis in developing rats was studied following chronic dosing with triethyl tin (TET), at a level of 1.0 mg TET/kg body wt/day. Experiments included starved controls with body weights depressed by 17 to 40% to equal those of the TET-treated groups. Rats at ages of 16, 21, and 30 days showed decreases relative to well-nourished controls in body weight, forebrain weight, myelin yield, cerebroside level, and specific activity of brain 2',3'-cyclic nucleotide-3'-phosphohydrolase when dosed with TET. At 30 days, myelin and cerebroside yields were reduced by approximately 55%, while CNP activity was reduced by less than 20%. No differences in the forebrain myelin protein composition between control, starved, and TET animals were noted. The rate of myelin protein synthesis relative to brain total protein (assayed by incorporation of intracranially injected [3H]glycine into brain homogenate and myelin proteins) was decreased in the TET rats in proportion to the decreased yield of myelin, but no particular myelin protein was preferentially affected. Matching starved controls exhibited similar body weight decreases, less pronounced forebrain weight decreases, and little or no decrease in myelin concentration. There was a relative increase in the myelin protein synthesis rate in the starved rats, indicating preferential utilization of limited protein precursors for myelin protein synthesis. Spinal cord myelin was also decreased in the TET rats, but less severely than in the forebrain. At all ages optic, but not sciatic, nerves showed decreases in myelin concentration with TET treatment. We conclude that TET inhibits forebrain growth and CNS myelination more severely than can be accounted for by a general metabolic insult.

Triethyl tin-induced myelin oedema: an intermediate swelling state detected by X-ray diffraction

“…5-10 mM Ca +2 or tetracaine (Melchior et al, 1979), 1.4 M dimethylsulphoxide (Kirschner & Caspar, 1975), and 250/~M HgC12 (Kirschner & Ganser, 1982). The 4/~M TET level is similar to that found in brains of developing rats chronically dosed with drinking water containing 10 mg TET/litre (Blaker et al, 1981). These investigators did not examine any morphological parameters but did observe biochemical changes reflecting a decreased level of myelination.…”

“…Our data on CO 2 production indicate that the metabolic capacity of the nerves is retained when the preparations are incubated overnight in nutrients and balanced salt solutions. TET is known to induce myelin oedema in vivo (reviewed by Torack et al, 1970; see also Watanabe, 1980;Blaker et al, 1981) and in vitro (Graham et al, 1975). TET has also been shown to facilitate anion transport across both natural and artificial membranes .…”

“…Electron microscopic studies on acute or chronic triethyl tin (TET) intoxication in adult rats (reviewed by Torack et al, 1970), adult mice (reviewed by Watanabe, 1980), the developing rat (Blaker et al, 1981), and in myelinating cultures of mouse spinal cord (Graham et al, 1975) reveal central nervous system demyelination that is characterized by a splitting of the lamellar myelin at the intraperiod line with subsequent fluid accumulation and widespread intramyelinic vacuole fgrmation. Similar effects have been reported in the peripheral nervous system after chronic TET dosage (Graham et al, 1976).…”

Inhibition of peroxisomal beta‐oxidation and brain development in rats

“…For a weight loss in our range, brain myelin losses of 13.5% (Fishman et al, 1971), 75% at all ages (Wiggins et al, 1976), 16% (Reddy et al, 19791, 40% (Fuller et al, 1984), and 60-70% (Yeh, 1988) are reported. Blaker et al (1981) even report a stimulated myelin production in mild undernourishment from 16 to 30 days of age.…”

Stereological Methods for Estimating the Myelin Sheaths of the Myelinated Fibers in White Matter

“…To detect the exact reason that leads to the decline of the myelinated fiber length in the white matter of aged brains, the myelin sheath ultrastructure of the myelinated fibers in white matter needs to be investigated with accurate quantitative methods. Beside the possible age-related changes of myelin sheaths, researchers have found that the changes of the myelin sheaths occurred as a result of experimental toxicity produced by Cuprizone, triethyltin, and isolecithin (Malamud and Hirano, 1973;Blakemore, 1978;Blaker et al, 1981;Chang, 1990;Ludwin, 1995;Irvine and Blakemore, 2006;Franco-Pons et al, 2007;Skripuletz et al, 2008), in patients with severe diabetes (Tamura and Parry, 1994;Myers, 1998), and in genetically engineered mice that had either an excess or a deficit of proteolipid protein (Monuki and Lemke, 1995;Anderson et al, 1998;Karim et al, 2007). It is well known that multiple sclerosis, a disease suffered by adults, is characterized by demyelination, inflammation, gliosis, and a variable loss of axons (Ludwin, 2000;Kuhlmann et al, 2008;Irvine and Blakemore, 2008).…”