The expression and binding of kainate receptors is modified in different brain regions by glutamate neurotoxicity during postnatal rat development

Abstract

Kainic acid receptor (KA-R) subunits are differentially expressed during brain development, and they modulate both neural growth and survival. High concentrations of glutamate in the brain can induce neuronal injury through these receptors, altering normal development. However, it is unclear whether KAR subunit expression itself is also modified by neonatal exposure to high glutamate. To analyze this, monosodium glutamate (4mg/g of body weight) was subcutaneously administered on postnatal days 1, 3, 5 and 7, and the expression of GluR5, GluR6, KA1 and KA2, as well as [3H]-kainic acid (KA-R) binding, was evaluated on postnatal days 14, 21, 30 and 60 in different regions of rat brain. As a result, high levels of GluR5 expression associated with strong [3H]-kainic acid binding were observed on postnatal days 30 and 60 in the cerebral cortex of rats exposed to glutamate. Similarly, the changes induced by glutamate administration in the expression of the KA1 and KA2 subunits were paralleled by those of [3H]-kainic acid binding in the striatum at postnatal days 21 and 30. In contrast, while KAR subunits were over expressed in the hippocampus, no changes were observed in [3H]-kainic acid binding in adult rats that had been exposed to glutamate. Therefore, glutamate modifies both the expression of kainic acid receptor subunits and kainic acid binding in a determined spatial and temporal manner, which may be indicative of a regional susceptibility to glutamate neurotoxicity.