{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:59:16Z","timestamp":1790366356172,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development and Innovation Office","award":["OTKA K124558"],"award-info":[{"award-number":["OTKA K124558"]}]},{"name":"National Research, Development and Innovation Office","award":["NIH-NINDS-1SC2NS124907-01"],"award-info":[{"award-number":["NIH-NINDS-1SC2NS124907-01"]}]},{"name":"National Research, Development and Innovation Office","award":["NIH-NINDS-1R15NS116478"],"award-info":[{"award-number":["NIH-NINDS-1R15NS116478"]}]},{"name":"U.S. National Institutes of Health","award":["OTKA K124558"],"award-info":[{"award-number":["OTKA K124558"]}]},{"name":"U.S. National Institutes of Health","award":["NIH-NINDS-1SC2NS124907-01"],"award-info":[{"award-number":["NIH-NINDS-1SC2NS124907-01"]}]},{"name":"U.S. National Institutes of Health","award":["NIH-NINDS-1R15NS116478"],"award-info":[{"award-number":["NIH-NINDS-1R15NS116478"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endogenous anticonvulsant mechanisms represent a reliable and currently underdeveloped strategy against recurrent seizures and may recall novel original therapeutics. Here, we investigated whether the intensification of the astroglial Glu-GABA exchange mechanism by application of the GABA precursor putrescine (PUT) may be effective against convulsive and non-convulsive seizures. We explored the potential of PUT to inhibit spontaneous spike-and-wave discharges (SWDs) in WAG\/Rij rats, a genetic model of absence epilepsy. Significant shortening of SWDs in response to intraperitoneally applied PUT has been observed, which could be antagonized by blocking GAT-2\/3-mediated astrocytic GABA release with the specific inhibitor SNAP-5114. Direct application of exogenous GABA also reduced SWD duration, suggesting that PUT-triggered astroglial GABA release through GAT-2\/3 may be a critical step in limiting seizure duration. PUT application also dose-dependently shortened seizure-like events (SLEs) in the low-[Mg2+] in vitro model of temporal lobe epilepsy. SNAP-5114 reversed the antiepileptic effect of PUT in the in vitro model as well, further confirming that PUT reduces seizure duration by triggering glial GABA release. In accordance, we observed that PUT specifically reduces the frequency of excitatory synaptic potentials, suggesting that it specifically acts at excitatory synapses. We also identified that PUT specifically eliminated the tonic depolarization-induced desynchronization of SLEs. Since PUT is an important source of glial GABA and we previously showed significant GABA release, it is suggested that the astroglial Glu-GABA exchange mechanism plays a key role in limiting ictal discharges, potentially opening up novel pathways to control seizure propagation and generalization.<\/jats:p>","DOI":"10.3390\/ijms23158191","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T21:20:59Z","timestamp":1658784059000},"page":"8191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Putrescine Intensifies Glu\/GABA Exchange Mechanism and Promotes Early Termination of Seizures"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-5686","authenticated-orcid":false,"given":"Zsolt","family":"Kov\u00e1cs","sequence":"first","affiliation":[{"name":"Department of Biology, Savaria University Centre, ELTE E\u00f6tv\u00f6s Lor\u00e1nd University, K\u00e1rolyi G\u00e1sp\u00e1r t\u00e9r 4, 9700 Szombathely, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serguei N.","family":"Skatchkov","sequence":"additional","affiliation":[{"name":"Department of Physiology, Universidad Central del Caribe, Bayamon, PR 00960, USA"},{"name":"Department of Biochemistry, Universidad Central del Caribe, Bayamon, PR 00960, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Functional Pharmacology Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Magyar Tud\u00f3sok K\u00f6r\u00fatja 2, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2679-0103","authenticated-orcid":false,"given":"Saif","family":"Qahtan","sequence":"additional","affiliation":[{"name":"Functional Pharmacology Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Magyar Tud\u00f3sok K\u00f6r\u00fatja 2, 1117 Budapest, Hungary"},{"name":"Hevesy Gy\u00f6rgy PhD School of Chemistry, ELTE E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter s\u00e9t\u00e1ny 1\/A, 1117 Budapest, Hungary"},{"name":"College of Science, University of Al-Qadisiyah, Al-Diwaniyah 58001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0079-4042","authenticated-orcid":false,"given":"Miguel P.","family":"M\u00e9ndez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Universidad Central del Caribe, Bayamon, PR 00960, USA"},{"name":"Natural Sciences Department, University of Puerto Rico in Aguadilla, Aguadilla, PR 00604, USA"},{"name":"Department of Science and Technology, Antilles Adventist University, Mayag\u00fcez, PR 00681, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6778-408X","authenticated-orcid":false,"given":"Christian J.","family":"Malpica-Nieves","sequence":"additional","affiliation":[{"name":"Department of Physiology, Universidad Central del Caribe, Bayamon, PR 00960, USA"},{"name":"Department of Biochemistry, Universidad Central del Caribe, Bayamon, PR 00960, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misty J.","family":"Eaton","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Universidad Central del Caribe, Bayamon, PR 00960, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9873-7155","authenticated-orcid":false,"given":"Julianna","family":"Kardos","sequence":"additional","affiliation":[{"name":"Functional Pharmacology Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Magyar Tud\u00f3sok K\u00f6r\u00fatja 2, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"H\u00e9ja","sequence":"additional","affiliation":[{"name":"Functional Pharmacology Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Magyar Tud\u00f3sok K\u00f6r\u00fatja 2, 1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.neuroscience.2003.08.051","article-title":"Neocortical seizures: Initiation, development and cessation","volume":"123","author":"Timofeev","year":"2004","journal-title":"Neuroscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1111\/j.1528-1167.2006.00622.x","article-title":"How long do most seizures last? 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