Ontogenetic development of kainate neurotoxicity: correlates with glutamatergic innervation.
Stereotaxic injection of kainic acid into the striatum of adult rats causes degeneration of neurons intrinsic to the striatum but spares axons of passage and of termination of extrinsic neurons. Neurochemical and histologic studies demonstrate that striatal neurons are almost insensitive to kainate at 7 days after birth and that their vulnerability increases with age; by 3 weeks after birth, striatal injection of kainate produces a lesion comparable to that of the adult. The intensity and duration of the acute behavioral response to kainate also increases with age. The maturational increase in striatal neuronal sensitivity to kainate correlates with the development of glutamatergic innervation to the striatum, as measured by [3H]glutamate uptake by synaptosomes, and with the development of a postsynaptic, high-affinity receptor site for kainate. These ontogenetic studies provide additional evidence that kainate's neurotoxicity is a receptor-mediated event related to glutamatergic innervation of vulnerable neurons.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D007608:Kainic Acid / Q000633:toxicity*; D018377:Neurotransmitter Agents / Q000378:metabolism; D011759:Pyrrolidines / Q000633:toxicity*; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D005971:Glutamates; D018377:Neurotransmitter Agents; D011759:Pyrrolidines; D017981:Receptors, Neurotransmitter; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D007608:Kainic Acid