Glial regulation of alpha 7-type nicotinic acetylcholine receptor expression in cultured rat cortical neurons.
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Primary embryonic cortical cultures were used as an in vitro model to evaluate the influence of glia on developmental expression of alpha 7-type nicotinic acetylcholine receptors in rat brain. In cells cultured in serum-containing medium without mitotic inhibitors, specific 125I-alpha-bungarotoxin binding to alpha 7-type nicotinic receptors was maximal 4-8 days after plating. Treatment with 5'-fluorodeoxyuridine (80 microM) from 1 to 3 days in vitro significantly reduced glial proliferation and concomitantly increased 125I-alpha-bungarotoxin binding, whereas plating onto a glial bed layer decreased binding. There was no significant binding to pure glial cultures. Treatment-induced changes in neuronal binding resulted from alterations in receptor density, with no change in affinity. 5'-Fluorodeoxyuridine treatment also increased cellular expression of alpha 7 receptor mRNA but had no effect on N-[3H]methylscopolamine binding to muscarinic receptors. Glial conditioned medium decreased 125I-alpha-bungarotoxin binding in both control and 5'-fluorodeoxyuridine-treated cultures, suggesting the release of a soluble factor that inhibits alpha 7-type nicotinic receptor expression. An additional mechanism of glial regulation may involve removal of glutamate from the surrounding medium, as added glutamate (200 microM) increased 125I-alpha-bungarotoxin binding in astrocyte-poor cultures but not in those that were astrocyte enriched. These results suggest that glia may serve a physiological role in regulating alpha 7-type nicotinic receptors in developing brain.
author list (cited authors)
Jensen, J. J., Winzer-Serhan, U. H., & Leslie, F. M.
complete list of authors
Jensen, JJ||Winzer-Serhan, UH||Leslie, FM