Estradiol modulation of kainic acid-induced calcium elevation in neonatal hippocampal neurons.
The developing hippocampus of both males and females is exposed to high levels of the gonadal steroid estradiol. The impact of this estradiol exposure on developing hippocampal neurons is essentially unknown. In the rat, the newborn hippocampus is relatively insensitive to excitotoxic brain injury, which in adults is associated with the release of amino acids, in particular glutamate, resulting in a significant increase in intracellular calcium and eventual cell death. We have shown previously in the rat that administration of the glutamate agonist, kainic acid (KA), on the day of birth results in limited hippocampal damage, which is ameliorated by treatment with the gonadal steroid, estradiol. We now show that KA induces an increase in intracellular calcium through L-type voltage-sensitive calcium channels early in development and, later in development, through polyamine-sensitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors with a modest increase through N-methyl-D-aspartate receptors. Pretreatment with the gonadal steroid, estradiol, decreases the percentage of neurons responding to KA and decreases the peak amplitude of the calcium transient early in development but has no effect later in development. Taken together, these data suggest that there is a developmental shift in the route of KA-induced intracellular calcium and estradiol modulates KA-induced intracellular calcium to a time restricted to early development, but whether this is the basis of the neuroprotective effect of estradiol remains to be determined.
Hilton
Genell D
GD
Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road Northwest, Research Building, Room WG-03, Washington, D.C. 20057, USA. gdh4@georgetown.edu
Bambrick
Linda L
LL
Thompson
Scott M
SM
McCarthy
Margaret M
MM
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004958:Estradiol / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D002118:Calcium; D004958:Estradiol; D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid; D007608:Kainic Acid; D011073:Polyamines; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid