Developmental changes in calpain activity, GluR1 receptors and in the effect of kainic acid treatment in rat brain.
The cellular distribution of calpain activation and glutamate receptor 1 (GluR1) subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic 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 subunits. In the first postnatal week, most brain regions exhibited high levels of calpain activity that progressively decreased during the following weeks. The highest levels of spectrin breakdown product immunoreactivity were observed in the somata and proximal dendrites of hippocampal pyramidal cells, non-pyramidal neurons in stratum oriens, and cortical neurons. In general, during the first two postnatal weeks, kainic acid treatment induced a decrease in spectrin breakdown product immunoreactivity in neuronal cell bodies and an increase in dendritic fields. Obvious elevation in spectrin breakdown product immunoreactivity in selective non-pyramidal cells in stratum oriens started at postnatal day 14, and was further evidenced by postnatal day 21. Likewise, massive calpain activation in subpopulations of neurons in some thalamic nuclei, amygdala, and pyriform cortex was observed after the third postnatal week. GluR1 subunits were highly expressed throughout the forebrain 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 neurons, with the non-pyramidal neurons in layers IV through VI exhibiting the densest immunolabelling. In the first two postnatal weeks, the somata of hippocampal pyramidal neurons exhibited intense GluR1 immunostaining that became more dendritic in the subsequent developmental period. While hilar cells exhibited a similar developmental pattern as CA regions, the molecular layer of dentate gyrus exhibited weak immunoreactivity from postnatal day 7 to postnatal day 14. The early increase in GluR1 immunoreactivity in hippocampal pyramidal layer following kainic acid treatment occurred throughout the developmental period, while the later decrease in CA regions, amygdala, and pyriform cortex was observed only in postnatal day 21 animals. The combined immunocytochemical studies of spectrin breakdown product localization and GluR1 expression indicate that calpain activation might play an important role in synaptic formation, developmental regulation of synaptic plasticity, and neuronal vulnerability to excitotoxicity during postnatal development. Moreover, calpain-mediated modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors might underlie these processes.
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Neuroscience Program, University of Southern California, Los Angeles 90089-2520, USA.
Chen
J
J
Baudry
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002154:Calpain / Q000378:metabolism*; D002452:Cell Count / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D013049:Spectrin / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D013049:Spectrin; D002154:Calpain; D007608:Kainic Acid