Exposure to methylmercury in utero: effects on biochemical development of catecholamine neurotransmitter systems.
Administration of methylmercury to pregnant rats resulted in major alterations in synaptic dynamics of brain dopamine systems in the offspring which were prominent even at doses of the organomercurial which did not produce acute toxicity, fetal or neonatal death, low birth weight or reduced litter sizes. The abnormalities were typified by shortfalls in both the levels and turnover rate of the transmitter in vivo, accompanied by elevations in synaptic uptake as assessed in synaptosomal preparations in vitro. These effects were not apparent in the immediate postnatal period but instead showed a delayed onset beginning at about the time of weaning. Methylmercury exposure displayed selectivity in that central noradrenergic systems showed only the synaptic uptake alterations without changes in transmitter levels or turnover; targeted interactions were also apparent in peripheral sympathetic pathways to the heart and kidney. The threshold dose required to elicit damage to biochemical development of neurotransmitter systems was the same as that to alter more generalized cellular development, as assessed through measurements of brain ornithine decarboxylase activity. These studies indicate that neurochemical damage produced by prenatal exposure of the developing organism to methylmercury involves transmitter-selective alterations in synaptic dynamics and function which may contribute to adverse behavioral outcomes; the underlying mechanisms, however, do not necessarily reflect actions of the organomercurial which are primary or specific to these particular neuronal tissues.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000201:enzymology / Q000254:growth & development*; D002395:Catecholamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000378:metabolism; D008767:Methylmercury Compounds / Q000633:toxicity*; D009206:Myocardium / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D008767:Methylmercury Compounds; D018377:Neurotransmitter Agents; D014446:Tyrosine 3-Monooxygenase; D009955:Ornithine Decarboxylase; D004298:Dopamine; D009638:Norepinephrine