DEVELOPMENTAL-CHANGES IN CALPAIN ACTIVITY, GLUR1 RECEPTORS AND IN THEEFFECT OF KAINIC ACID TREATMENT IN RAT-BRAIN

The cellular distribution of calpain activation and glutamate receptor 1 (GluR1) subunits of lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropio nic acid receptors and their alterations following kainic acid-induced seizure were evaluated during postnatal development using antibodies specific for spectrin breakdown product and the C-terminus of GluR1 su bunits. In the first postnatal week, most brain regions exhibited high levels of calpain activity that progressively decreased during the fo llowing weeks. The highest levels of spectrin breakdown product immuno reactivity were observed in the somata and proximal dendrites of hippo campal pyramidal cells, non-pyramidal neurons in stratum oriens, and c ortical neurons. In general, during the first two postnatal weeks, kai nic acid treatment induced a decrease in spectrin breakdown product im munoreactivity in neuronal cell bodies and an increase in dendritic fi elds. Obvious elevation in spectrin breakdown product immunoreactivity in selective non-pyramidal cells in stratum oriens started at postnat al day 14, and was further evidenced by postnatal day 21. Likewise, ma ssive calpain activation in subpopulations of neurons in some thalamic nuclei, amygdala, and pyriform cortex was observed after the third po stnatal week. GluR1 subunits were highly expressed throughout the fore brain in the first postnatal week, further increased during the second postnatal week, decreased thereafter, and reached adult levels after postnatal day 21. In cortex, intense GluR1 immunostaining was found in the somata and proximal processes of pyramidal and non-pyramidal neur ons, with the non-pyramidal neurons in layers IV through VI exhibiting the densest immunolabelling. In the first two postnatal weeks, the so mata of hippocampal pyramidal neurons exhibited intense GluR1 immunost aining that became more dendritic in the subsequent developmental peri od. While hilar cells exhibited a similar developmental pattern as CA regions, the molecular layer of dentate gyrus exhibited weak immunorea ctivity from postnatal day 7 to postnatal day 14. The early increase i n GluR1 immunoreactivity in hippocampal pyramidal layer following kain ic acid treatment occurred throughout the developmental period, while the later decrease in CA regions, amygdala, and pyriform cortex was ob served only in postnatal day 21 animals. The combined immunocytochemic al studies of spectrin breakdown product localization and GluR1 expres sion indicate that calpain activation might play an important role in synaptic formation, developmental regulation of synaptic plasticity, a nd neuronal vulnerability to excitotoxicity during postnatal developme nt. Moreover, calpain-mediated modulation of lpha-amino-3-hydroxy-5-me thyl-4-isoxazolepropionic acid receptors might underlie these processe s. (C) 1997 IBRO. Published by Elsevier Science Ltd.