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Neurosteroids and Focal Epileptic Disorders
Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. The most studied neurosteroids-allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC)-are known to modulate GABA...
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| Published in: | International journal of molecular sciences 2020-12, Vol.21 (24), p.9391 |
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| container_start_page | 9391 |
| container_title | International journal of molecular sciences |
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| creator | Lévesque, Maxime Biagini, Giuseppe Avoli, Massimo |
| description | Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. The most studied neurosteroids-allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC)-are known to modulate GABA
receptor-mediated transmission, thus playing a role in controlling neuronal network excitability. Given the role of GABA
signaling in epileptic disorders, neurosteroids have profound effects on seizure generation and play a role in the development of chronic epileptic conditions (i.e., epileptogenesis). We review here studies showing the effects induced by neurosteroids on epileptiform synchronization in in vitro brain slices, on epileptic activity in in vivo models, i.e., in animals that were made epileptic with chemoconvulsant treatment, and in epileptic patients. These studies reveal that neurosteroids can modulate ictogenesis and the occurrence of pathological network activity such as interictal spikes and high-frequency oscillations (80-500 Hz). Moreover, they can delay the onset of spontaneous seizures in animal models of mesial temporal lobe epilepsy. Overall, this evidence suggests that neurosteroids represent a new target for the treatment of focal epileptic disorders. |
| doi_str_mv | 10.3390/ijms21249391 |
| format | article |
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receptor-mediated transmission, thus playing a role in controlling neuronal network excitability. Given the role of GABA
signaling in epileptic disorders, neurosteroids have profound effects on seizure generation and play a role in the development of chronic epileptic conditions (i.e., epileptogenesis). We review here studies showing the effects induced by neurosteroids on epileptiform synchronization in in vitro brain slices, on epileptic activity in in vivo models, i.e., in animals that were made epileptic with chemoconvulsant treatment, and in epileptic patients. These studies reveal that neurosteroids can modulate ictogenesis and the occurrence of pathological network activity such as interictal spikes and high-frequency oscillations (80-500 Hz). Moreover, they can delay the onset of spontaneous seizures in animal models of mesial temporal lobe epilepsy. Overall, this evidence suggests that neurosteroids represent a new target for the treatment of focal epileptic disorders.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21249391</identifier><identifier>PMID: 33321734</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animal models ; Animals ; Anticonvulsants - pharmacology ; Anticonvulsants - therapeutic use ; Brain slice preparation ; Brain Waves - drug effects ; Cholesterol ; Epilepsy ; Epilepsy, Temporal Lobe - drug therapy ; Epilepsy, Temporal Lobe - metabolism ; Epilepsy, Temporal Lobe - physiopathology ; Firing pattern ; Glial cells ; Humans ; Neuronal-glial interactions ; Neurosteroids ; Neurosteroids - pharmacology ; Neurosteroids - therapeutic use ; Oscillations ; Pregnanolone ; Pregnenolone ; Review ; Seizures ; Synaptic Transmission - drug effects ; Synchronism ; Synchronization ; Temporal lobe ; γ-Aminobutyric acid A receptors</subject><ispartof>International journal of molecular sciences, 2020-12, Vol.21 (24), p.9391</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-c26a96f0d28e2d7aec0b268c7a339f9cbdadbc2121d6bc2aeffdf380c08fb023</citedby><cites>FETCH-LOGICAL-c412t-c26a96f0d28e2d7aec0b268c7a339f9cbdadbc2121d6bc2aeffdf380c08fb023</cites><orcidid>0000-0002-7130-2511</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2470130748/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2470130748?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25733,27903,27904,36991,36992,44569,53769,53771,74872</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33321734$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lévesque, Maxime</creatorcontrib><creatorcontrib>Biagini, Giuseppe</creatorcontrib><creatorcontrib>Avoli, Massimo</creatorcontrib><title>Neurosteroids and Focal Epileptic Disorders</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. The most studied neurosteroids-allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC)-are known to modulate GABA
receptor-mediated transmission, thus playing a role in controlling neuronal network excitability. Given the role of GABA
signaling in epileptic disorders, neurosteroids have profound effects on seizure generation and play a role in the development of chronic epileptic conditions (i.e., epileptogenesis). We review here studies showing the effects induced by neurosteroids on epileptiform synchronization in in vitro brain slices, on epileptic activity in in vivo models, i.e., in animals that were made epileptic with chemoconvulsant treatment, and in epileptic patients. These studies reveal that neurosteroids can modulate ictogenesis and the occurrence of pathological network activity such as interictal spikes and high-frequency oscillations (80-500 Hz). Moreover, they can delay the onset of spontaneous seizures in animal models of mesial temporal lobe epilepsy. Overall, this evidence suggests that neurosteroids represent a new target for the treatment of focal epileptic disorders.</description><subject>Animal models</subject><subject>Animals</subject><subject>Anticonvulsants - pharmacology</subject><subject>Anticonvulsants - therapeutic use</subject><subject>Brain slice preparation</subject><subject>Brain Waves - drug effects</subject><subject>Cholesterol</subject><subject>Epilepsy</subject><subject>Epilepsy, Temporal Lobe - drug therapy</subject><subject>Epilepsy, Temporal Lobe - metabolism</subject><subject>Epilepsy, Temporal Lobe - physiopathology</subject><subject>Firing pattern</subject><subject>Glial cells</subject><subject>Humans</subject><subject>Neuronal-glial interactions</subject><subject>Neurosteroids</subject><subject>Neurosteroids - pharmacology</subject><subject>Neurosteroids - therapeutic use</subject><subject>Oscillations</subject><subject>Pregnanolone</subject><subject>Pregnenolone</subject><subject>Review</subject><subject>Seizures</subject><subject>Synaptic Transmission - drug effects</subject><subject>Synchronism</subject><subject>Synchronization</subject><subject>Temporal lobe</subject><subject>γ-Aminobutyric acid A receptors</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNpdkUtLAzEUhYMoVqs71zLgRtDRPMZkshGktioU3XQfMnloysxkTGYE_73R1lJdnQv343DOvQCcIHhFCIfXbtlEjHDBCUc74AAVGOcQUra7NY_AYYxLCDHBN3wfjAghGDFSHICLZzMEH3sTvNMxk63OZl7JOpt2rjZd71R276IP2oR4BPasrKM5XusYLGbTxeQxn788PE3u5rkqEO5zhank1EKNS4M1k0bBCtNSMZnyWq4qLXWlUmSkaVJprNWWlFDB0lYp4hjcrmy7oWqMVqbtg6xFF1wjw6fw0om_m9a9iVf_IRijhBcsGZyvDYJ_H0zsReOiMnUtW-OHKHDBIMWcQ57Qs3_o0g-hTe1-KEQgK8pEXa4olU4Vg7GbMAiK7yeI7Sck_HS7wAb-vTr5Amxfg3E</recordid><startdate>20201210</startdate><enddate>20201210</enddate><creator>Lévesque, Maxime</creator><creator>Biagini, Giuseppe</creator><creator>Avoli, Massimo</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7130-2511</orcidid></search><sort><creationdate>20201210</creationdate><title>Neurosteroids and Focal Epileptic Disorders</title><author>Lévesque, Maxime ; Biagini, Giuseppe ; Avoli, Massimo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-c26a96f0d28e2d7aec0b268c7a339f9cbdadbc2121d6bc2aeffdf380c08fb023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Anticonvulsants - pharmacology</topic><topic>Anticonvulsants - therapeutic use</topic><topic>Brain slice preparation</topic><topic>Brain Waves - drug effects</topic><topic>Cholesterol</topic><topic>Epilepsy</topic><topic>Epilepsy, Temporal Lobe - drug therapy</topic><topic>Epilepsy, Temporal Lobe - metabolism</topic><topic>Epilepsy, Temporal Lobe - physiopathology</topic><topic>Firing pattern</topic><topic>Glial cells</topic><topic>Humans</topic><topic>Neuronal-glial interactions</topic><topic>Neurosteroids</topic><topic>Neurosteroids - pharmacology</topic><topic>Neurosteroids - therapeutic use</topic><topic>Oscillations</topic><topic>Pregnanolone</topic><topic>Pregnenolone</topic><topic>Review</topic><topic>Seizures</topic><topic>Synaptic Transmission - drug effects</topic><topic>Synchronism</topic><topic>Synchronization</topic><topic>Temporal lobe</topic><topic>γ-Aminobutyric acid A receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lévesque, Maxime</creatorcontrib><creatorcontrib>Biagini, Giuseppe</creatorcontrib><creatorcontrib>Avoli, Massimo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest research library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lévesque, Maxime</au><au>Biagini, Giuseppe</au><au>Avoli, Massimo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neurosteroids and Focal Epileptic Disorders</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-12-10</date><risdate>2020</risdate><volume>21</volume><issue>24</issue><spage>9391</spage><pages>9391-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. 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receptor-mediated transmission, thus playing a role in controlling neuronal network excitability. Given the role of GABA
signaling in epileptic disorders, neurosteroids have profound effects on seizure generation and play a role in the development of chronic epileptic conditions (i.e., epileptogenesis). We review here studies showing the effects induced by neurosteroids on epileptiform synchronization in in vitro brain slices, on epileptic activity in in vivo models, i.e., in animals that were made epileptic with chemoconvulsant treatment, and in epileptic patients. These studies reveal that neurosteroids can modulate ictogenesis and the occurrence of pathological network activity such as interictal spikes and high-frequency oscillations (80-500 Hz). Moreover, they can delay the onset of spontaneous seizures in animal models of mesial temporal lobe epilepsy. Overall, this evidence suggests that neurosteroids represent a new target for the treatment of focal epileptic disorders.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33321734</pmid><doi>10.3390/ijms21249391</doi><orcidid>https://orcid.org/0000-0002-7130-2511</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2020-12, Vol.21 (24), p.9391 |
| issn | 1422-0067 1661-6596 1422-0067 |
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| source | Publicly Available Content Database; PubMed Central |
| subjects | Animal models Animals Anticonvulsants - pharmacology Anticonvulsants - therapeutic use Brain slice preparation Brain Waves - drug effects Cholesterol Epilepsy Epilepsy, Temporal Lobe - drug therapy Epilepsy, Temporal Lobe - metabolism Epilepsy, Temporal Lobe - physiopathology Firing pattern Glial cells Humans Neuronal-glial interactions Neurosteroids Neurosteroids - pharmacology Neurosteroids - therapeutic use Oscillations Pregnanolone Pregnenolone Review Seizures Synaptic Transmission - drug effects Synchronism Synchronization Temporal lobe γ-Aminobutyric acid A receptors |
| title | Neurosteroids and Focal Epileptic Disorders |
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