Stress and corticosteroid modulation of seizures and synaptic inhibition in the hippocampus.
The role of stress hormones in the initiation of epileptic seizures has been studied extensively in the past decade, with conflicting observations, from suppression to exacerbation of spontaneous seizures. We have now studied the effects of an acute stress on reactivity of juvenile rats to kainic acid (KA), which produces epileptic seizures. With a short (30s) stress-KA delay, stress exacerbated epilepsy via activation of mineralocorticosterone receptors (MR). With a long (60 min) stress-KA delay, seizures were suppressed through activation of a glucocorticosterone receptor (GR). In a parallel study with CA1 pyramidal neurons in acute hippocampal slices, activation of MRs reduced the frequency of mIPSCs, whereas activation of GRs produced a slow onset, 2.5 fold increase in amplitudes of mIPSCs. GR effects were not mediated by protein synthesis, but did require activation of some protein kinases. These experiments suggest that stress can either facilitate or suppress seizures, in a time and receptor dependent manner.
Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel. nicola.maggio@sheba.health.gov.il
Nicola
N
Maggio
Menahem
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Segal
D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000450:Aldosterone / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001703:Biophysics; D004195:Disease Models, Animal; D004347:Drug Interactions; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D007608:Kainic Acid / Q000009:adverse effects; D008297:Male; D015735:Mifepristone / Q000494:pharmacology / Q000627:therapeutic use; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000473:pathology*; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use; D013315:Stress, Psychological / Q000473:pathology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D004791:Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D015735:Mifepristone; D000450:Aldosterone; D007608:Kainic Acid