Silencing of dentate gyrus inhibits mossy fiber sprouting and prevents epileptogenesis through NDR2 kinase in pentylenetetrazole kindling rat model of TLE
Epileptogenesis is a potential process. Mossy fiber sprouting (MFS) contributes to epileptogenesis. Silencing of the dentate gyrus (DG) suppressed spontaneous seizures model of epilepsy and hyperactivity of granule cells resulted in MFS in vitro. However, the role of DG's excitability in epilep...
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| description | Epileptogenesis is a potential process. Mossy fiber sprouting (MFS) contributes to epileptogenesis. Silencing of the dentate gyrus (DG) suppressed spontaneous seizures model of epilepsy and hyperactivity of granule cells resulted in MFS in vitro. However, the role of DG's excitability in epileptogenesis have not yet been well explored, and underlying mechanisms has not been elucidated. Using chemical genetics, we studied whether MFS and epileptogenesis could be modulated by silencing of DG in the PTZ kindling rat model of epilepsy. MFS and protein expression was measured by Timm staining, Western blotting, and Immunofluorescence. Previous studies demonstrated that MFS and epileptogenesis could be modulated by a regulator of axonal growth (e.g. RGMa, PTEN). NDR2 kinase regulate neuronal polarity and prevents the formation of supernumerary axons in the hippocampus. We experimentally confirmed chemogenetic inhibition in DG resulted in decreased MFS and NDR2 expression, and alleviated epileptogenesis. Furthermore, our results showed that injection of AVV vector expressing NDR2 into DG induced upregulation of NDR2 in the hippocampus, and over expression of NDR2 in the hippocampus promote MFS and block protective effect of chemogenetic silencing of DG on epileptogenesis. Overall, we concluded that silencing of DG inhibits MFS and prevents epileptogenesis through NDR2 in the hippocampus in the PTZ kindling rat model of TLE, thereby providing a possible strategy to prevent epileptogenesis. |
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Mossy fiber sprouting (MFS) contributes to epileptogenesis. Silencing of the dentate gyrus (DG) suppressed spontaneous seizures model of epilepsy and hyperactivity of granule cells resulted in MFS in vitro. However, the role of DG's excitability in epileptogenesis have not yet been well explored, and underlying mechanisms has not been elucidated. Using chemical genetics, we studied whether MFS and epileptogenesis could be modulated by silencing of DG in the PTZ kindling rat model of epilepsy. MFS and protein expression was measured by Timm staining, Western blotting, and Immunofluorescence. Previous studies demonstrated that MFS and epileptogenesis could be modulated by a regulator of axonal growth (e.g. RGMa, PTEN). NDR2 kinase regulate neuronal polarity and prevents the formation of supernumerary axons in the hippocampus. We experimentally confirmed chemogenetic inhibition in DG resulted in decreased MFS and NDR2 expression, and alleviated epileptogenesis. Furthermore, our results showed that injection of AVV vector expressing NDR2 into DG induced upregulation of NDR2 in the hippocampus, and over expression of NDR2 in the hippocampus promote MFS and block protective effect of chemogenetic silencing of DG on epileptogenesis. Overall, we concluded that silencing of DG inhibits MFS and prevents epileptogenesis through NDR2 in the hippocampus in the PTZ kindling rat model of TLE, thereby providing a possible strategy to prevent epileptogenesis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0284359</identifier><identifier>PMID: 37043471</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Axonogenesis ; Axons ; Biology and Life Sciences ; Brain ; Complications and side effects ; Convulsions & seizures ; Dentate gyrus ; Dentate Gyrus - metabolism ; Diagnosis ; Epilepsy ; Epilepsy - chemically induced ; Epilepsy - genetics ; Epilepsy - metabolism ; Excitability ; Genetics ; Genomes ; GPI-Linked Proteins - metabolism ; Granule cells ; Health aspects ; Hippocampus ; Hippocampus - metabolism ; Immunofluorescence ; Kinases ; Kindling ; Kindling, Neurologic - metabolism ; Laboratory animals ; Medicine and Health Sciences ; Membrane Proteins - metabolism ; Modelling ; Mossy Fibers, Hippocampal ; Nerve Tissue Proteins - metabolism ; Pentylenetetrazole ; Pentylenetetrazole - adverse effects ; Phosphotransferases - metabolism ; Polarity ; PTEN protein ; Rats ; Rats, Sprague-Dawley ; Research and Analysis Methods ; Seizures ; Seizures (Medicine) ; Supernumerary ; Surgery ; Western blotting</subject><ispartof>PloS one, 2023-04, Vol.18 (4), p.e0284359-e0284359</ispartof><rights>Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Zhang et al 2023 Zhang et al</rights><rights>2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c642t-49d1dbb656ea0ea5a8d4e8270379aeb7e2cec7b523d0643b5bcf5f95f12a19553</cites><orcidid>0000-0001-9973-4239</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10096303/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10096303/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37043471$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mortensen, Andreia Cristina Karklin</contributor><creatorcontrib>Zhang, Chen</creatorcontrib><creatorcontrib>He, Zixian</creatorcontrib><creatorcontrib>Tan, Zheren</creatorcontrib><creatorcontrib>Tian, Fafa</creatorcontrib><title>Silencing of dentate gyrus inhibits mossy fiber sprouting and prevents epileptogenesis through NDR2 kinase in pentylenetetrazole kindling rat model of TLE</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Epileptogenesis is a potential process. Mossy fiber sprouting (MFS) contributes to epileptogenesis. Silencing of the dentate gyrus (DG) suppressed spontaneous seizures model of epilepsy and hyperactivity of granule cells resulted in MFS in vitro. However, the role of DG's excitability in epileptogenesis have not yet been well explored, and underlying mechanisms has not been elucidated. Using chemical genetics, we studied whether MFS and epileptogenesis could be modulated by silencing of DG in the PTZ kindling rat model of epilepsy. MFS and protein expression was measured by Timm staining, Western blotting, and Immunofluorescence. Previous studies demonstrated that MFS and epileptogenesis could be modulated by a regulator of axonal growth (e.g. RGMa, PTEN). NDR2 kinase regulate neuronal polarity and prevents the formation of supernumerary axons in the hippocampus. We experimentally confirmed chemogenetic inhibition in DG resulted in decreased MFS and NDR2 expression, and alleviated epileptogenesis. Furthermore, our results showed that injection of AVV vector expressing NDR2 into DG induced upregulation of NDR2 in the hippocampus, and over expression of NDR2 in the hippocampus promote MFS and block protective effect of chemogenetic silencing of DG on epileptogenesis. Overall, we concluded that silencing of DG inhibits MFS and prevents epileptogenesis through NDR2 in the hippocampus in the PTZ kindling rat model of TLE, thereby providing a possible strategy to prevent epileptogenesis.</description><subject>Animals</subject><subject>Axonogenesis</subject><subject>Axons</subject><subject>Biology and Life Sciences</subject><subject>Brain</subject><subject>Complications and side effects</subject><subject>Convulsions & seizures</subject><subject>Dentate gyrus</subject><subject>Dentate Gyrus - metabolism</subject><subject>Diagnosis</subject><subject>Epilepsy</subject><subject>Epilepsy - chemically induced</subject><subject>Epilepsy - genetics</subject><subject>Epilepsy - metabolism</subject><subject>Excitability</subject><subject>Genetics</subject><subject>Genomes</subject><subject>GPI-Linked Proteins - metabolism</subject><subject>Granule cells</subject><subject>Health aspects</subject><subject>Hippocampus</subject><subject>Hippocampus - metabolism</subject><subject>Immunofluorescence</subject><subject>Kinases</subject><subject>Kindling</subject><subject>Kindling, Neurologic - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Chen</au><au>He, Zixian</au><au>Tan, Zheren</au><au>Tian, Fafa</au><au>Mortensen, Andreia Cristina Karklin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Silencing of dentate gyrus inhibits mossy fiber sprouting and prevents epileptogenesis through NDR2 kinase in pentylenetetrazole kindling rat model of TLE</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2023-04-12</date><risdate>2023</risdate><volume>18</volume><issue>4</issue><spage>e0284359</spage><epage>e0284359</epage><pages>e0284359-e0284359</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Epileptogenesis is a potential process. Mossy fiber sprouting (MFS) contributes to epileptogenesis. Silencing of the dentate gyrus (DG) suppressed spontaneous seizures model of epilepsy and hyperactivity of granule cells resulted in MFS in vitro. However, the role of DG's excitability in epileptogenesis have not yet been well explored, and underlying mechanisms has not been elucidated. Using chemical genetics, we studied whether MFS and epileptogenesis could be modulated by silencing of DG in the PTZ kindling rat model of epilepsy. MFS and protein expression was measured by Timm staining, Western blotting, and Immunofluorescence. Previous studies demonstrated that MFS and epileptogenesis could be modulated by a regulator of axonal growth (e.g. RGMa, PTEN). NDR2 kinase regulate neuronal polarity and prevents the formation of supernumerary axons in the hippocampus. We experimentally confirmed chemogenetic inhibition in DG resulted in decreased MFS and NDR2 expression, and alleviated epileptogenesis. Furthermore, our results showed that injection of AVV vector expressing NDR2 into DG induced upregulation of NDR2 in the hippocampus, and over expression of NDR2 in the hippocampus promote MFS and block protective effect of chemogenetic silencing of DG on epileptogenesis. Overall, we concluded that silencing of DG inhibits MFS and prevents epileptogenesis through NDR2 in the hippocampus in the PTZ kindling rat model of TLE, thereby providing a possible strategy to prevent epileptogenesis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>37043471</pmid><doi>10.1371/journal.pone.0284359</doi><tpages>e0284359</tpages><orcidid>https://orcid.org/0000-0001-9973-4239</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Axonogenesis Axons Biology and Life Sciences Brain Complications and side effects Convulsions & seizures Dentate gyrus Dentate Gyrus - metabolism Diagnosis Epilepsy Epilepsy - chemically induced Epilepsy - genetics Epilepsy - metabolism Excitability Genetics Genomes GPI-Linked Proteins - metabolism Granule cells Health aspects Hippocampus Hippocampus - metabolism Immunofluorescence Kinases Kindling Kindling, Neurologic - metabolism Laboratory animals Medicine and Health Sciences Membrane Proteins - metabolism Modelling Mossy Fibers, Hippocampal Nerve Tissue Proteins - metabolism Pentylenetetrazole Pentylenetetrazole - adverse effects Phosphotransferases - metabolism Polarity PTEN protein Rats Rats, Sprague-Dawley Research and Analysis Methods Seizures Seizures (Medicine) Supernumerary Surgery Western blotting |
| title | Silencing of dentate gyrus inhibits mossy fiber sprouting and prevents epileptogenesis through NDR2 kinase in pentylenetetrazole kindling rat model of TLE |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T16%3A11%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Silencing%20of%20dentate%20gyrus%20inhibits%20mossy%20fiber%20sprouting%20and%20prevents%20epileptogenesis%20through%20NDR2%20kinase%20in%20pentylenetetrazole%20kindling%20rat%20model%20of%20TLE&rft.jtitle=PloS%20one&rft.au=Zhang,%20Chen&rft.date=2023-04-12&rft.volume=18&rft.issue=4&rft.spage=e0284359&rft.epage=e0284359&rft.pages=e0284359-e0284359&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0284359&rft_dat=%3Cgale_plos_%3EA745266353%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2800117063&rft_id=info:pmid/37043471&rft_galeid=A745266353&rft_doaj_id=oai_doaj_org_article_88121726915e46dc806f2e634ea9d387&rfr_iscdi=true |