Biochemical mechanisms of developmental neurotoxicity of methylmercury.
Methylmercury has been designated a "behavioral teratogen" because of its ability to evoke abnormalities in the absence of gross morphological damage to the developing brain. Recent work indicates that exposure to doses of methylmercury associated with neurobehavioral actions causes early alterations in brain ornithine decarboxylase, an enzyme whose activity is related to the coordination of cellular maturation. These effects are followed by regionally-targeted perturbation of cell replication and differentiation, indicated by measurements of nucleic acid and protein synthesis and levels. Neurobehavioral disturbances are associated with postnatal alterations in synaptogenesis and synaptic activity, as exemplified by studies in catecholaminergic pathways. Thus, methylmercury alters neurotransmitter uptake and turnover in presynaptic terminals, as well as development of postsynaptic adrenergic receptor binding sites. These changes result in aberrant signal transmission across the synapse, with consequent effects on synaptic function and ultimately on the communication of trophic developmental signals which ordinarily pass from neuron to target tissue. Although the specific linkages among the various biochemical effects of developmental exposure to methylmercury remain to be elucidated, studies of this type can serve as a model with which to understand the subcellular mechanisms underlying behavioral teratogenesis.
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D005333:Fetus / Q000187:drug effects*; D006321:Heart / Q000294:innervation; D008767:Methylmercury Compounds / Q000633:toxicity*; D009420:Nervous System / Q000187:drug effects* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000187:drug effects
D008767:Methylmercury Compounds; D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D009955:Ornithine Decarboxylase