Progesterone Receptor Regulation of Seizures
Abstract number :
1.178
Submission category :
3. Neurophysiology / 3F. Animal Studies
Year :
2019
Submission ID :
2421173
Source :
www.aesnet.org
Presentation date :
12/7/2019 6:00:00 PM
Published date :
Nov 25, 2019, 12:14 PM
Authors :
Shinnosuke Shiono, University of Virginia; John M. Williamson, University of Virginia; Jaideep Kapur, University of Virginia; Suchitra Joshi, University of Virginia
Rationale: Menstrual cycle-linked hormonal fluctuations regulate seizure frequency. We determined the role of PRs in regulating susceptibility to SE and the frequency of spontaneous seizures in epileptic animals. Methods: Epileptic adult female Sprague Dawley rats were used. Seizures were monitored by continuous video-EEG. Basal seizure frequency was monitored for 2 weeks and then the animals were treated with progesterone (P, 50 mg/kg/day, ip) for a week; RU-486 (RU, 10 mg/kg/day) or vehicle (V) were administered 30 min before progesterone. The seizure frequency during the week subsequent to progesterone treatment week was determined to evaluate the effect of withdrawal. Finally, the susceptibility of female rats with global deletion of PRs to lithium-pilocarpine-induced SE was assessed. Results: RU treatment blocked withdrawal-induced seizure exacerbation (doubling of seizure frequency during withdrawal); 15% P+RU-treated animals (n=13) experienced seizure exacerbation as compared to 57% of P+V-treated animals (n=14, p<0.05). More seizures were recorded from P+V-treated animals during withdrawal (57+-16) than at baseline (30+-9, n=14, p=0.03), whereas seizures remained stable in P+RU-treated animals (41+-16 vs 43+-13 respectively, p=0.39).We also determined whether global deletion of PRs (KO) affected susceptibility to SE. Estrous cycle and associated hormonal changes were comparable between PR KO and littermate WT animals. SE was induced in animals in estrus stage of the cycle. The latency to seizure onset was similar in the WT and KO animals (756 +- 50 s, n=4 vs 646 +- 78 s, n=5). The duration of electrographic SE also appeared to be comparable between WT (458 +- 109 min, n=4) and KO animals (381 +- 89 min, n=5). However, the power of EEG in delta to gamma frequencies tended to be lower in the KO animals than that in the WT animals. The WT animals also continued to have spikes at a frequency of 3-9 Hz after SE has ended. Similar spikes were not observed in the KO animals. Conclusions: PR activation regulates recurrent spontaneous seizures and contributes to progesterone withdrawal-induced seizure exacerbation. Deletion of PRs reduced the severity of SE. Funding: R01 NS 110863R01 NS 040337R01 NS 044370
Neurophysiology