Effect of trimethyltin on ornithine decarboxylase in various regions of the mouse brain

doi:10.1016/0378-4274(87)90042-7

Toxicology Letters

Volume 36, Issue 1, March 1987, Pages 67-72

https://doi.org/10.1016/0378-4274(87)90042-7 Get rights and content

Abstract

Male C57B1/6N mice, 8–10 weeks old were given a single oral dose of 0, 1.0 or 3.0 mg/kg body weight of trimethyltin hydroxide (TMT). Levels of ornithine decarboxylase (ODC) activity were measured in several brain areas, 1, 2 and 7 days later. The lower dose of TMT produced a decrease of ODC in the caudate nucleus and hippocampus at all time points studied. Hypothalamus, cerebellum and brain stem levels of this enzyme were unaltered. At the higher dose of TMT, ODC activity in hippocampus, cerebellum and brain stem were increased relative to controls at 1 and 2 days after treatment, while other regions were not significantly affected. These elevated ODC levels returned to control values within 7 days. Thus, trimethyltin treatment causes changes in ODC activity in a region and dose-specific manner.

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Developmental profiles of ornithine decarboxylase activity in the hippocampus, neocortex and cerebellum: Modulation following lead exposure
1994, International Journal of Developmental Neuroscience
Ornithine decarboxylase (ODC) is a growth-associated enzyme which is critical for cell growth and transformation. ODC activity follows a specific ontogenetic pattern of activity in distinct brain regions according to their developmental stage. Perturbations in the pattern of ODC activity have been associated with brain damage including arrested cerebral growth. Modulations in the pattern of ODC activity were examined in the hippocampus, neocortex and cerebellum of neonatal rats (PND 3, 6, 9, 15) exposed via the dam to 0.2% lead-acetate (Pb²⁺ prenatally (gestational day 13 to birth), postnatally (PND 1–15) or perinatally (gestational day 13 to PND 15). Prenatal exposure to Pb²⁺ perturbed the profile of ODC activity in all three brain regions examined, while postnatal exposure to Pb²⁺ resulted in prolonged stimulations of ODC activity in the cerebellum. Following prenatal exposure, these effects were manifested as a stimulation of ODC activity in the hippocampus, a repression of activity in the neocortex and a combination of these effects in the cerebellum. Perinatal exposure to Pb²⁺ transiently modulated the pattern of ODC activity similarly in all three brain regions, in a characteristic manner irrespective of their developmental stage. These Pb²⁺-induced modulations of ODC activity suggest that polyamine-dependent processes may play a significant role in the manifestation of Pb²⁺-induced neurotoxicity dependent upon developmental factors at specific exposure periods.
Correlations between developmental ornithine decarboxylase gene expression and enzyme activity in the rat brain
1993, Developmental Brain Research
The rise and decline in cerebral ODC activity during specific stages of development has been attributed to cytoplasmic intermediates which regulate ornithine decarboxylase activity. Here we examine whether transcriptional regulation contributes to the production of the developmental profiles of ODC activity. Postnatal cerebellar and neocortical tissue were obtained from Long-Evans hooded rats at postnatal days (PND) 5, 10, 15, 20, 25, 30, 90 and probed for ODC and actin gene expression, by Northern analysis. Our results indicate that ODC gene expression in the cerebellum was elevated at PND 5 and 10 followed by a gradual drop to the adult low levels by PND 20. By contrast, high levels of ODC gene expression in the neocortex were seen at PND 5 with an abrupt decrease at day 10 to low adult levels. The expression of the ODC gene in the neocortex follows closely the pattern for the ODC enzyme activity; however, it tends to remain elevated longer in the cerebellum. The levels of actin gene expression exhibited a distinct developmental profile in the postnatally developing cerebellum. However, actin mRNA levels remained unchanged in the neocortex, consistent with the prenatal development of this region. Our findings suggest that ODC gene expression may play an important role in the production of the ontogenetic patterns of ODC activity.
Ischemia-induced disturbances of polyamine synthesis
1993, Progress in Brain Research
This chapter discusses ischemia-induced disturbances in polyamine synthesis. It discusses the periods of time during which changes take place and the relationship of changes in polyamine synthesis to the duration of ischemia. Pharmacological interventions reducing ischemia-induced disturbances in polyamine synthesis are discussed. Emphasis is put on the possible role of ischemia-induced alterations in polyamine metabolism in the process of recovery from the metabolic stress produced either by cerebral ischemia or in the manifestation of neuronal necrosis. Transient cerebral ischemia causes a disturbance of polyamine synthesis that is characterized by a sharp increase in ornithine decarboxylase and decrease in S-adenosylmethionine decarboxylase activity. The result is an overshoot in putrescine formation and a reduction in spermine levels. In addition, evidence is presented that polyamines are released from the intracellular compartment during ischemia and following prolonged recirculation in severely damaged areas. Because of the main features of ischemia-induced disturbances in polyamine synthesis and the reactions known to be influenced by these altered polyamine profiles it is suggested that these changes play a role in the manifestation of ischemia-induced neuronal necrosis.
Myelin basic protein-mRNA used to monitor trimethyltin neurotoxicity in rats
1991, Toxicology and Applied Pharmacology
Trimethyltin (TMT) is an alkyltin that targets neurons of the limbic system. A gene probe (i.e., mRNA) for myelin basic protein (MBP), a major component of central nervous system myelin, was used to monitor this toxic neuropathy in Sprague-Dawley rats. Animals were administered a single intraperitoneal injection of TMT-hydroxide at a neuropathic (8.0 mg/kg/body wt) or nonneuropathic (0.8 mg/kg/body wt) dose and sampled at 1, 3, or 7 days postexposure to correlate the progression of hippocampal neuropathology with probe (i.e., MBP-mRNA) levels. Microscopic examination of the brain showed only moderate but progressive damage over the 7-day postexposure period in animals treated with the neuropathic dose. Neuronal loss was first observed in the dendate gyrus and CA₄ at 1 day postexposure, and progressed to the CA_3c sector at 3 and 7 days postexposure. Elsewhere in the brain, minimal involvement of the entorhinal cortex neurons occurred 3 days postexposure and intensified by 7 days. No histological damage was seen at the nonneuropathic (0.8 mg/kg) dose. For gene probe analysis, the brain was divided into anterior and posterior halves. In rats treated with the neuropathic dose of TMT, the anterior brain showed progressive depressions of MBP-mRNA levels over the 1-, 3-, and 7-day postexposure period that correlated with increasing hippocampal neuropathology. The posterior brain showed no significant changes in MBP-mRNA levels with respect to that of controls over the same time period. At the nonneuropathic dose (0.8 mg/kg) a significant depression of MBP-mRNA levels occurred in the anterior brain at 7 days postexposure in the absence of overt histological damage.
Polyamine metabolism in reversible cerebral ischemia: effect of α-difluoromethylornithine
1988, Brain Research
Severe forebrain ischemia was produced in rats by occluding both carotid and vertebral arteries. Following 30 min ischemia brains were recirculated for 8 or 24 h. Twelve animals subjected to 8 or 24 h recirculation (n = 6, each group) were given α-difluoromethylornithine (DFMO; injected intraperitoneally) immediately before samples were taken from the cerebellum, cortex, caudatoputamen and hippocampus. Samples from the left hemisphere were used for measuring ornithine decarboxylase (ODC) activity, and those from the right hemisphere for determining putrescine profiles. During recirculation ODC activity increased markedly in all brain structures, the most pronounced change being in the caudatoputamen after 8 h recirculation. Putrescine increased drastically after 8 h and even more after 24 h recirculation. DFMO-treatment significantly reduced ODC activity after 8 h recirculation and following 24 h recirculation. Putrescine, however, was significantly reduced following 24 h but not after 8 h recirculation. The discrepancy between reduction in ODC activity and putrescine levels in DFMO-treated animals was not prominent in the hippocampus after 8 h recirculation: here DFMO reduced ODC activity to control values without affecting putrescine levels. The results suggest that the observed overshoot in putrescine formation following ischemia is only partly caused by activation of ODC.
Ornithine decarboxylase in human brain: Influence of aging, regional distribution, and Alzheimer's disease
1998, Journal of Neurochemistry

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Effect of trimethyltin on ornithine decarboxylase in various regions of the mouse brain

Abstract

Environ. Res.

Toxicol. Appl. Pharmacol.

Organotin compounds: industrial applications and biological investigation

Environ. Health Perspect.

Toxicity and health effects of selected organotin compounds: a review

Environ. Health Perspect.

Technoeconomic and environmental assessment of industrial organotin compounds

Neurotoxicology

Trimethyltin poisoning: report of two cases

Int. Arch. Occup. Environ. Health

Neurotoxic effects of occupational exposure to organotins

Am. J. Psychiatry

Neuropathology of mouse hippocampus in acute trimethyltin intoxication

Neurobehav. Toxicol. Teratol.

The behavioral and neuropathologic sequelae of intoxication by trimethyltin compounds in the rat

Am. J. Pathol.

Effects of postnatal trimethyltin or triethyltin treatment on CNS catecholamine, GABA, and acetylcholine system in the rat

J. Neurochem.

Cholinergic and dopaminergic alterations in the mouse central nervous system following acute trimethyltin exposure

Acta Pharmacol. Toxicol.