{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T01:19:10Z","timestamp":1783387150452,"version":"3.54.6"},"reference-count":53,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS 040337"],"award-info":[{"award-number":["NS 040337"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS 044370"],"award-info":[{"award-number":["NS 044370"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS 110863"],"award-info":[{"award-number":["NS 110863"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Emerging evidence raises the possibility that progesterone receptor (PR) signaling may contribute to the reproductive hormone fluctuation\u2013linked seizure precipitation, called catamenial epilepsy. Therefore, we studied PR isoform expression in limbic regions involved in temporal lobe epilepsy and the effect of PR activation on neuronal activity and seizures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated PR expression in the limbic regions, entorhinal cortex (EC), hippocampus, and amygdala in female rats using quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR). A selective agonist, Nestorone (16\u2010methylene\u201017 alpha\u2010acetoxy\u201019\u2010nor\u2010pregn\u20104\u2010ene\u20103,20\u2010dione) activated PRs, and the effect on excitability and \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic acid receptor (AMPAR)\u2013mediated synaptic transmission of EC neurons was studied using electrophysiology. Finally, we assessed PR regulation of epileptic seizures and status epilepticus (SE) induced by lithium\u2010pilocarpine in female rats with the global deletion of PRs (PR knockout; PRKO) using video electroencephalography (\u2010EEG).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Limbic regions EC, hippocampus, and amygdala robustly expressed PR messenger RNA (mRNA). Nestorone (16\u2010methylene\u201017 alpha\u2010acetoxy\u201019\u2010nor\u2010pregn\u20104\u2010ene\u20103,20\u2010dione) treatment reduced the action potential threshold of layer II\/III EC neurons and increased the frequency of AMPA receptor\u2013mediated synaptic currents of ovariectomized and estrogen\u2010primed female rats. Female rats lacking PRs (PRKO) experienced a shorter duration, less intense, and less fatal SE than wild\u2010type (WT) animals. Furthermore, Nestorone treatment caused seizure exacerbation in the WT epileptic animals, but not in the PRKO epileptic animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Activation of PRs expressed in the EC and hippocampus increased neuronal excitability and worsened seizures. These receptors may play a role in catamenial epilepsy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16970","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T07:44:52Z","timestamp":1624520692000},"page":"1946-1959","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Limbic progesterone receptor activity enhances neuronal excitability and seizures"],"prefix":"10.1111","volume":"62","author":[{"given":"Shinnosuke","family":"Shiono","sequence":"first","affiliation":[{"name":"Department of Neurology University of Virginia\u2010HSC Charlottesville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia\u2010HSC Charlottesville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamal","family":"Batabyal","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia\u2010HSC Charlottesville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Labuz","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia\u2010HSC Charlottesville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia\u2010HSC Charlottesville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8608-1352","authenticated-orcid":false,"given":"Jaideep","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia\u2010HSC Charlottesville VA USA"},{"name":"Department of Neuroscience University of Virginia\u2010HSC Charlottesville VA USA"},{"name":"UVA Brain Institute University of Virginia\u2010HSC Charlottesville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3524-2061","authenticated-orcid":false,"given":"Suchitra","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia\u2010HSC Charlottesville VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-128X(03)00126-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2008.02.001"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000338668"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1300"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.138.10.5456"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22361"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(00)00410-X"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2826.2003.01088.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.12.009"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50830"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903360210"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(85)90401-7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-128X(00)00119-7"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1426"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2007.11.014"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1997.tb01197.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181ae7adf"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2015.02.024"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1601825113"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-415-5_34"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06923"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-12-07680.1994"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.09.046"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21207"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-96-1-219"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110090200"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.7.10.1244"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1621\/nrs.07009"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-37-11641.2003"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1469"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0920-1211(90)90085-A"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1991.tb05533.x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-10-06301.1995"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2012.04.014"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2018.02.031"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128313"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)02414-9"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21989"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1063(1997)7:2<146::AID-HIPO4>3.0.CO;2-L"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901690306"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.23145"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(91)90011-O"},{"key":"e_1_2_9_45_1","first-page":"2336","article-title":"Parallel pathways of seizure generalization","volume":"142","author":"Dabrowska N","year":"2019","journal-title":"Brain"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.03.017"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23570"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25635"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3785"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00014.2003"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21826"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0272-17.2017"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021014-071753"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1973.sp010273"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16970","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.16970","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16970","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T16:21:29Z","timestamp":1693326089000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.16970"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,24]]},"references-count":53,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1111\/epi.16970"],"URL":"https:\/\/doi.org\/10.1111\/epi.16970","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,24]]},"assertion":[{"value":"2020-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}