{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T16:37:11Z","timestamp":1789835831197,"version":"4.0.1"},"reference-count":113,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH K12 NRCDP Program","doi-asserted-by":"publisher","award":["K12NS080223"],"award-info":[{"award-number":["K12NS080223"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH K12 NRCDP Program","doi-asserted-by":"publisher","award":["UL1TR002529"],"award-info":[{"award-number":["UL1TR002529"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Indiana Clinical and Translational Sciences Institute","award":["K12NS080223"],"award-info":[{"award-number":["K12NS080223"]}]},{"name":"Indiana Clinical and Translational Sciences Institute","award":["UL1TR002529"],"award-info":[{"award-number":["UL1TR002529"]}]},{"DOI":"10.13039\/100006975","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K12NS080223"],"award-info":[{"award-number":["K12NS080223"]}],"id":[{"id":"10.13039\/100006975","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006975","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR002529"],"award-info":[{"award-number":["UL1TR002529"]}],"id":[{"id":"10.13039\/100006975","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mesial temporal lobe epilepsy (mTLE) is a life-threatening condition characterized by recurrent hippocampal seizures. mTLE can develop after exposure to risk factors such as febrile seizure, trauma, and infection. Within the latent period between exposure and onset of epilepsy, pathological remodeling events occur that contribute to epileptogenesis. The molecular mechanisms responsible are currently unclear. We used the mouse intrahippocampal kainite model of mTLE to investigate transcriptional dysregulation in the ipsilateral and contralateral dentate gyrus (DG), representing the epileptogenic zone (EZ) and peri-ictal zone (PIZ). DG were analyzed after 3, 7, and 14 days by RNA sequencing. In both the EZ and PIZ, transcriptional dysregulation was dynamic over the epileptogenic period with early expression of genes representing cell signaling, migration, and proliferation. Canonical Wnt signaling was upregulated in the EZ and PIZ at 3 days. Expression of inflammatory genes differed between the EZ and PIZ, with early expression after 3 days in the PIZ and delayed expression after 7\u201314 days in the EZ. This suggests that critical gene changes occur early in the hippocampal seizure network and that Wnt signaling may play a role within the latent epileptogenic period. These findings may help to identify novel therapeutic targets that could prevent epileptogenesis.<\/jats:p>","DOI":"10.3390\/ijms231912030","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T21:07:11Z","timestamp":1665436031000},"page":"12030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Transcriptome Profiling of the Hippocampal Seizure Network Implicates a Role for Wnt Signaling during Epileptogenesis in a Mouse Model of Temporal Lobe Epilepsy"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6782-2776","authenticated-orcid":false,"given":"Muriel D.","family":"Mardones","sequence":"first","affiliation":[{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9847-0099","authenticated-orcid":false,"given":"Kunal","family":"Gupta","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Epilepsy surveillance among adults\u201419 States, Behavioral Risk Factor Surveillance System, 2005","volume":"57","author":"Kobau","year":"2008","journal-title":"MMWR Surveill. Summ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1056\/NEJM200002033420503","article-title":"Early identification of refractory epilepsy","volume":"342","author":"Kwan","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1136\/jnnp.2004.045690","article-title":"The natural history of epilepsy: An epidemiological view","volume":"75","author":"Kwan","year":"2004","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1111\/j.1528-1167.2008.01579.x","article-title":"The prevalence of epilepsy and pharmacoresistant epilepsy in adults: A population-based study in a Western European country","volume":"49","author":"Picot","year":"2008","journal-title":"Epilepsia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11060-018-2862-0","article-title":"Tumor-related epilepsy: Epidemiology, pathogenesis and management","volume":"139","author":"Chen","year":"2018","journal-title":"J. Neurooncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e80","DOI":"10.1212\/WNL.0b013e31826aa902","article-title":"Febrile seizures: Possible outcomes","volume":"79","author":"French","year":"2012","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1046\/j.1528-1157.44.s10.4.x","article-title":"Epidemiology of posttraumatic epilepsy: A critical review","volume":"44","author":"Frey","year":"2003","journal-title":"Epilepsia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1136\/pgmj.2005.041426","article-title":"Post-stroke seizure and post-stroke epilepsy","volume":"82","author":"Myint","year":"2006","journal-title":"Postgrad. Med. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1684\/epd.2017.0916","article-title":"Epilepsy after cerebral infection: Review of the literature and the potential for surgery","volume":"19","author":"Ramantani","year":"2017","journal-title":"Epileptic Disord. Int. Epilepsy J. Videotape"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6606","DOI":"10.1038\/ncomms7606","article-title":"Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline","volume":"6","author":"Cho","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1111\/j.1460-9568.2005.04386.x","article-title":"Disruption of the neurogenic potential of the dentate gyrus in a mouse model of temporal lobe epilepsy with focal seizures","volume":"22","author":"Kralic","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1523\/JNEUROSCI.5655-09.2010","article-title":"The developmental stage of dentate granule cells dictates their contribution to seizure-induced plasticity","volume":"30","author":"Kron","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1523\/JNEUROSCI.17-10-03727.1997","article-title":"Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus","volume":"17","author":"Parent","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/epi4.12044","article-title":"The intrahippocampal kainate mouse model of mesial temporal lobe epilepsy: Lack of electrographic seizure-like events in sham controls","volume":"2","author":"Twele","year":"2017","journal-title":"Epilepsia Open"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/epi4.2","article-title":"The effects of carbamazepine in the intrahippocampal kainate model of temporal lobe epilepsy depend on seizure definition and mouse strain","volume":"1","author":"Twele","year":"2016","journal-title":"Epilepsia Open"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.yebeh.2015.11.027","article-title":"Significant effects of sex, strain, and anesthesia in the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy","volume":"55","author":"Twele","year":"2016","journal-title":"Epilepsy Behav."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/978-94-017-8914-1_4","article-title":"What is a seizure focus?","volume":"813","author":"Nadler","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3776","DOI":"10.1523\/JNEUROSCI.2193-17.2018","article-title":"Electrophysiological Evidence for the Development of a Self-Sustained Large-Scale Epileptic Network in the Kainate Mouse Model of Temporal Lobe Epilepsy","volume":"38","author":"Sheybani","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3389\/fnsys.2010.00154","article-title":"From intracerebral EEG signals to brain connectivity: Identification of epileptogenic networks in partial epilepsy","volume":"4","author":"Wendling","year":"2010","journal-title":"Front. Syst. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1093\/brain\/awv372","article-title":"Temporal plus epilepsy is a major determinant of temporal lobe surgery failures","volume":"139","author":"Barba","year":"2016","journal-title":"Brain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1093\/brain\/awh221","article-title":"Temporal lobectomy: Long-term seizure outcome, late recurrence and risks for seizure recurrence","volume":"127","author":"McIntosh","year":"2004","journal-title":"Brain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/hipo.23268","article-title":"Multi-omics analysis suggests enhanced epileptogenesis in the Cornu Ammonis 3 of the pilocarpine model of mesial temporal lobe epilepsy","volume":"31","author":"Canto","year":"2021","journal-title":"Hippocampus"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"170061","DOI":"10.1038\/sdata.2017.61","article-title":"Transcriptional profile of hippocampal dentate granule cells in four rat epilepsy models","volume":"4","author":"Dingledine","year":"2017","journal-title":"Sci. Data"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ygeno.2016.04.001","article-title":"RNA-seq analysis of hippocampal tissues reveals novel candidate genes for drug refractory epilepsy in patients with MTLE-HS","volume":"107","author":"Dixit","year":"2016","journal-title":"Genomics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6930","DOI":"10.1038\/srep06930","article-title":"Profiling status epilepticus-induced changes in hippocampal RNA expression using high-throughput RNA sequencing","volume":"4","author":"Hansen","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1111\/j.1750-3639.2010.00414.x","article-title":"Proteomic profiling of the epileptic dentate gyrus","volume":"20","author":"Li","year":"2010","journal-title":"Brain Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Theilhaber, J., Rakhade, S.N., Sudhalter, J., Kothari, N., Klein, P., Pollard, J., and Jensen, F.E. (2013). Gene expression profiling of a hypoxic seizure model of epilepsy suggests a role for mTOR and Wnt signaling in epileptogenesis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074428"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"573575","DOI":"10.3389\/fneur.2020.573575","article-title":"Differential Glial Activation in Early Epileptogenesis-Insights From Cell-Specific Analysis of DNA Methylation and Gene Expression in the Contralateral Hippocampus","volume":"11","author":"Berger","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Alqurashi, R.S., Yee, A.S., Malone, T., Alrubiaan, S., Tam, M.W., Wang, K., Nandedwalla, R.R., Field, W., Alkhelb, D., and Given, K.S. (2021). A Warburg-like metabolic program coordinates Wnt, AMPK, and mTOR signaling pathways in epileptogenesis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0252282"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gupta, K., and Schnell, E. (2019). Neuronal network remodeling and Wnt pathway dysregulation in the intra-hippocampal kainate mouse model of temporal lobe epilepsy. PLoS ONE, 14.","DOI":"10.1101\/604975"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1021\/acschemneuro.2c00227","article-title":"Anticonvulsive and Neuroprotective Effects of Eupafolin in Rats Are Associated with the Inhibition of Glutamate Overexcitation and Upregulation of the Wnt\/beta-Catenin Signaling Pathway","volume":"13","author":"Jean","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"617143","DOI":"10.3389\/fnmol.2020.617143","article-title":"Chronic Intermittent Hypobaric Hypoxia Restores Hippocampus Function and Rescues Cognitive Impairments in Chronic Epileptic Rats via Wnt\/beta-catenin Signaling","volume":"13","author":"Sun","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3389\/fncel.2013.00224","article-title":"Wnts in adult brain: From synaptic plasticity to cognitive deficiencies","volume":"7","author":"Oliva","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/stem.3121","article-title":"Wnt5a promotes differentiation and development of adult-born neurons in the hippocampus by noncanonical Wnt signaling","volume":"38","author":"Arredondo","year":"2020","journal-title":"Stem Cells"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1159\/000345353","article-title":"Wnt signaling regulates intermediate precursor production in the postnatal dentate gyrus by regulating CXCR4 expression","volume":"34","author":"Choe","year":"2012","journal-title":"Dev. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14317","DOI":"10.1523\/JNEUROSCI.3206-07.2007","article-title":"Conditional knock-out of beta-catenin in postnatal-born dentate gyrus granule neurons results in dendritic malformation","volume":"27","author":"Gao","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/nature04108","article-title":"Wnt signalling regulates adult hippocampal neurogenesis","volume":"437","author":"Lie","year":"2005","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13041-016-0209-3","article-title":"Frizzled-1 receptor regulates adult hippocampal neurogenesis","volume":"9","author":"Mardones","year":"2016","journal-title":"Mol. Brain"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1093\/jnen\/61.10.903","article-title":"Differential regulation of cadherins and catenins during axonal reorganization in the adult rat CNS","volume":"61","author":"Fasen","year":"2002","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/cbf.3306","article-title":"Wnt\/beta-catenin signalling pathway mediated aberrant hippocampal neurogenesis in kainic acid-induced epilepsy","volume":"35","author":"Qu","year":"2017","journal-title":"Cell Biochem. Funct."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1093\/cercor\/bhr054","article-title":"Septotemporal position in the hippocampal formation determines epileptic and neurogenic activity in temporal lobe epilepsy","volume":"22","author":"Bielefeld","year":"2012","journal-title":"Cereb. Cortex"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1113\/JP270056","article-title":"In vivo evaluation of the dentate gate theory in epilepsy","volume":"593","author":"Armstrong","year":"2015","journal-title":"J. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/(SICI)1096-9861(19970901)385:3<385::AID-CNE4>3.0.CO;2-#","article-title":"Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats","volume":"385","author":"Buckmaster","year":"1997","journal-title":"J. Comp. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6273","DOI":"10.1073\/pnas.96.11.6273","article-title":"beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation","volume":"96","author":"Liu","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0925-4773(98)00134-8","article-title":"beta-TrCP is a negative regulator of Wnt\/beta-catenin signaling pathway and dorsal axis formation in Xenopus embryos","volume":"77","author":"Marikawa","year":"1998","journal-title":"Mech. Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0306-4522(98)00401-1","article-title":"Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice: Electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy","volume":"89","author":"Bouilleret","year":"1999","journal-title":"Neuroscience"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.expneurol.2005.08.010","article-title":"Seizures induce proliferation and dispersion of doublecortin-positive hippocampal progenitor cells","volume":"196","author":"Jessberger","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Okamoto, O.K., Janjoppi, L., Bonone, F.M., Pansani, A.P., da Silva, A.V., Scorza, F.A., and Cavalheiro, E.A. (2010). Whole transcriptome analysis of the hippocampus: Toward a molecular portrait of epileptogenesis. BMC Genom., 11.","DOI":"10.1186\/1471-2164-11-230"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1523\/JNEUROSCI.3212-04.2005","article-title":"Regulation of dendritic spine morphogenesis by insulin receptor substrate 53, a downstream effector of Rac1 and Cdc42 small GTPases","volume":"25","author":"Choi","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e159","DOI":"10.1212\/WNL.0000000000007753","article-title":"Epilepsy duration and seizure outcome in epilepsy surgery: A systematic review and meta-analysis","volume":"93","author":"Bjellvi","year":"2019","journal-title":"Neurology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13024-017-0193-9","article-title":"A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT\/PCP pathway","volume":"12","author":"Salasova","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4966","DOI":"10.1093\/hmg\/dds342","article-title":"LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6","volume":"21","author":"Berwick","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7711","DOI":"10.1038\/s41598-017-07394-3","article-title":"TGFbeta signaling is associated with changes in inflammatory gene expression and perineuronal net degradation around inhibitory neurons following various neurological insults","volume":"7","author":"Kim","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/ana.24147","article-title":"Losartan prevents acquired epilepsy via TGF-beta signaling suppression","volume":"75","author":"Cacheaux","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8927","DOI":"10.1523\/JNEUROSCI.0430-09.2009","article-title":"Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis","volume":"29","author":"Cacheaux","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-kappaB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1111\/j.1471-4159.2007.04863.x","article-title":"Nuclear factor-kappa B regulates seizure threshold and gene transcription following convulsant stimulation","volume":"103","author":"Lubin","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.nbd.2013.10.012","article-title":"Heat shock protein 70 protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus via inhibition of nuclear factor-kappaB activation-induced nitric oxide synthase II expression","volume":"62","author":"Chang","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1002\/jnr.22369","article-title":"Transcriptional upregulation of nitric oxide synthase II by nuclear factor-kappaB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus","volume":"88","author":"Chuang","year":"2010","journal-title":"J. Neurosci. Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Park, C.Y., Kim, H.S., Jang, J., Lee, H., Lee, J.S., Yoo, J.E., Lee, D.R., and Kim, D.W. (2013). ABCD2 is a direct target of beta-catenin and TCF-4: Implications for X-linked adrenoleukodystrophy therapy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056242"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1016\/j.cell.2012.03.047","article-title":"Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes","volume":"149","author":"Naito","year":"2012","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.bbrc.2018.06.045","article-title":"Circular RNA circ-CBFB promotes proliferation and inhibits apoptosis in chronic lymphocytic leukemia through regulating miR-607\/FZD3\/Wnt\/beta-catenin pathway","volume":"503","author":"Xia","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ponferrada, V.G., Fan, J., Vallance, J.E., Hu, S., Mamedova, A., Rankin, S.A., Kofron, M., Zorn, A.M., Hegde, R.S., and Lang, R.A. (2012). CRIM1 complexes with ss-catenin and cadherins, stabilizes cell-cell junctions and is critical for neural morphogenesis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032635"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1016\/j.joca.2019.07.007","article-title":"Exostosin-1 enhances canonical Wnt signaling activity during chondrogenic differentiation","volume":"27","author":"Wang","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"134","DOI":"10.12688\/f1000research.2-134.v2","article-title":"FAM129B is a novel regulator of Wnt\/beta-catenin signal transduction in melanoma cells","volume":"2","author":"Conrad","year":"2013","journal-title":"F1000Research"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/ng.2538","article-title":"Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation","volume":"45","author":"Morris","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_67","first-page":"951","article-title":"Comparative integromics on BMP\/GDF family","volume":"17","author":"Katoh","year":"2006","journal-title":"Int. J. Mol. Med."},{"key":"ref_68","first-page":"14","article-title":"The role of glypican-3 in regulating Wnt in hepatocellular carcinomas","volume":"1","author":"Gao","year":"2011","journal-title":"Cancer Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1111\/cas.14805","article-title":"KHDRBS3 promotes multi-drug resistance and anchorage-independent growth in colorectal cancer","volume":"112","author":"Ukai","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1002\/emmm.201101043","article-title":"Krueppel-like factor 15 regulates Wnt\/beta-catenin transcription and controls cardiac progenitor cell fate in the postnatal heart","volume":"4","author":"Noack","year":"2012","journal-title":"EMBO Mol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.cellsig.2018.08.020","article-title":"Wnt5a contributes to dectin-1 and LOX-1 induced host inflammatory response signature in Aspergillus fumigatus keratitis","volume":"52","author":"Che","year":"2018","journal-title":"Cell. Signal."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"17649","DOI":"10.1074\/jbc.M111.229427","article-title":"Matrix metalloproteinase (MMP)-9 induced by Wnt signaling increases the proliferation and migration of embryonic neural stem cells at low O2 levels","volume":"286","author":"Ingraham","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1126\/science.283.5405.1180","article-title":"Regulation of neurotrophin-3 expression by epithelial-mesenchymal interactions: The role of Wnt factors","volume":"283","author":"Patapoutian","year":"1999","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"22113","DOI":"10.1038\/srep22113","article-title":"The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma","volume":"6","author":"Cironi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e20882","DOI":"10.7554\/eLife.20882","article-title":"Constitutive scaffolding of multiple Wnt enhanceosome components by Legless\/BCL9","volume":"6","author":"Mieszczanek","year":"2017","journal-title":"Elife"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ydbio.2017.01.003","article-title":"The thyroid hormone nuclear receptors and the Wnt\/beta-catenin pathway: An intriguing liaison","volume":"422","author":"Skah","year":"2017","journal-title":"Dev. Biol"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s11515-012-1200-8","article-title":"Wntless in Wnt secretion: Molecular, cellular and genetic aspects","volume":"7","author":"Das","year":"2012","journal-title":"Front. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1007\/s00109-022-02216-0","article-title":"ZMIZ proteins: Partners in transcriptional regulation and risk factors for human disease","volume":"100","author":"Lomeli","year":"2022","journal-title":"J. Mol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4095","DOI":"10.1523\/JNEUROSCI.5508-05.2006","article-title":"Seizures accelerate functional integration of adult-generated granule cells","volume":"26","author":"Bromberg","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/S0006-3223(03)00700-5","article-title":"Chronic electroconvulsive seizure up-regulates beta-catenin expression in rat hippocampus: Role in adult neurogenesis","volume":"54","author":"Madsen","year":"2003","journal-title":"Biol. Psychiatry"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/j.0013-9580.2004.69103.x","article-title":"NBQX or topiramate treatment after perinatal hypoxia-induced seizures prevents later increases in seizure-induced neuronal injury","volume":"45","author":"Koh","year":"2004","journal-title":"Epilepsia"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"8154","DOI":"10.1523\/JNEUROSCI.21-20-08154.2001","article-title":"Decreased glutamate receptor 2 expression and enhanced epileptogenesis in immature rat hippocampus after perinatal hypoxia-induced seizures","volume":"21","author":"Sanchez","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1093\/emboj\/20.16.4500","article-title":"Negative regulation of the Wnt-beta-catenin pathway by the transcriptional repressor HBP1","volume":"20","author":"Sampson","year":"2001","journal-title":"EMBO J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"860","DOI":"10.3389\/fcell.2020.00860","article-title":"Role of Wnt Signaling in Adult Hippocampal Neurogenesis in Health and Disease","volume":"8","author":"Arredondo","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJM200108023450501","article-title":"A randomized, controlled trial of surgery for temporal-lobe epilepsy","volume":"345","author":"Wiebe","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00401-006-0187-0","article-title":"A new clinico-pathological classification system for mesial temporal sclerosis","volume":"113","author":"Blumcke","year":"2007","journal-title":"Acta Neuropathol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1111\/epi.12220","article-title":"International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: A Task Force report from the ILAE Commission on Diagnostic Methods","volume":"54","author":"Blumcke","year":"2013","journal-title":"Epilepsia"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.nbd.2005.01.020","article-title":"Increased number of neural progenitors in human temporal lobe epilepsy","volume":"19","author":"Crespel","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0006-8993(90)91601-C","article-title":"Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy","volume":"535","author":"Houser","year":"1990","journal-title":"Brain Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1046\/j.1528-1157.43.s.5.28.x","article-title":"Seizures decrease postnatal neurogenesis and granule cell development in the human fascia dentata","volume":"43","author":"Mathern","year":"2002","journal-title":"Epilepsia"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"5064","DOI":"10.1523\/JNEUROSCI.3014-18.2019","article-title":"Antagonizing Increased miR-135a Levels at the Chronic Stage of Experimental TLE Reduces Spontaneous Recurrent Seizures","volume":"39","author":"Vangoor","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13041-018-0376-5","article-title":"RNAseq analysis of hippocampal microglia after kainic acid-induced seizures","volume":"11","author":"Bosco","year":"2018","journal-title":"Mol. Brain"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0013-4694(72)90177-0","article-title":"Modification of seizure activity by electrical stimulation. II. Motor seizure","volume":"32","author":"Racine","year":"1972","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4701","DOI":"10.1523\/JNEUROSCI.5516-05.2006","article-title":"Reelin deficiency and displacement of mature neurons, but not neurogenesis, underlie the formation of granule cell dispersion in the epileptic hippocampus","volume":"26","author":"Heinrich","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.3109\/13880209.2013.803128","article-title":"Antiepileptogenic effect of curcumin on kainate-induced model of temporal lobe epilepsy","volume":"51","author":"Kiasalari","year":"2013","journal-title":"Pharm. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"226","DOI":"10.5607\/en.2018.27.3.226","article-title":"Morin Prevents Granule Cell Dispersion and Neurotoxicity via Suppression of mTORC1 in a Kainic Acid-induced Seizure Model","volume":"27","author":"Lee","year":"2018","journal-title":"Exp. Neurobiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1056\/NEJM199107113250203","article-title":"Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee","volume":"325","author":"Bradley","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/acem.14169","article-title":"Acetaminophen, Nonsteroidal Anti-inflammatory Drugs, or Combination of Both Analgesics in Acute Posttrauma Pain: A Randomized Controlled Trial","volume":"28","author":"Msolli","year":"2021","journal-title":"Acad. Emerg. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0306-4522(00)00017-8","article-title":"Neurodegenerative and morphogenic changes in a mouse model of temporal lobe epilepsy do not depend on the expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin","volume":"97","author":"Bouilleret","year":"2000","journal-title":"Neuroscience"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"D916","DOI":"10.1093\/nar\/gkaa1087","article-title":"GENCODE 2021","volume":"49","author":"Frankish","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Sherman","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_108","unstructured":"(2021). The Gene Ontology resource: Enriching a GOld mine. Nucleic Acids Res., 49, D325\u2013D334."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1002\/pro.3715","article-title":"Toward understanding the origin and evolution of cellular organisms","volume":"28","author":"Kanehisa","year":"2019","journal-title":"Protein Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: Integrating viruses and cellular organisms","volume":"49","author":"Kanehisa","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1089\/152791601750294344","article-title":"BioCarta","volume":"2","author":"Nishimura","year":"2001","journal-title":"Biotech Softw. Internet Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/12030\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:49:11Z","timestamp":1760143751000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/12030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,10]]},"references-count":113,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231912030"],"URL":"https:\/\/doi.org\/10.3390\/ijms231912030","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,10]]}}}