{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:44:20Z","timestamp":1773297860967,"version":"3.50.1"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Rodent kindling induced by PTZ is a widely used model of epileptogenesis and AED testing. Overlapping pathophysiological mechanisms may underlie epileptogenesis and other neuropsychiatric conditions. Besides epilepsy, AEDs are widely used in treating various neuropsychiatric disorders. Mechanisms of AEDs' long term action in these disorders are poorly understood. We describe here a<jats:italic>Drosophila<\/jats:italic>systems model of PTZ induced locomotor plasticity that is responsive to AEDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We empirically determined a regime in which seven days of PTZ treatment and seven days of subsequent PTZ discontinuation respectively cause a decrease and an increase in climbing speed of<jats:italic>Drosophila<\/jats:italic>adults. Concomitant treatment with NaVP and LEV, not ETH, GBP and VGB, suppressed the development of locomotor deficit at the end of chronic PTZ phase. Concomitant LEV also ameliorated locomotor alteration that develops after PTZ withdrawal. Time series of microarray expression profiles of heads of flies treated with PTZ for 12 hrs (beginning phase), two days (latent phase) and seven days (behaviorally expressive phase) showed only down-, not up-, regulation of genes; expression of 23, 2439 and 265 genes were downregulated, in that order. GO biological process enrichment analysis showed downregulation of transcription, neuron morphogenesis during differentiation, synaptic transmission, regulation of neurotransmitter levels, neurogenesis, axonogenesis, protein modification, axon guidance, actin filament organization etc. in the latent phase and of glutamate metabolism, cell communication etc. in the expressive phase. Proteomic interactome based analysis provided further directionality to these events. Pathway overrepresentation analysis showed enrichment of Wnt signaling and other associated pathways in genes downregulated by PTZ. Mining of available transcriptomic and proteomic data pertaining to established rodent models of epilepsy and human epileptic patients showed overrepresentation of epilepsy associated genes in our PTZ regulated set.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Systems biology ultimately aims at delineating and comprehending the functioning of complex biological systems in such details that predictive models of human diseases could be developed. Due to immense complexity of higher organisms, systems biology approaches are however currently focused on simpler organisms. Amenable to modeling, our model offers a unique opportunity to further dissect epileptogenesis-like plasticity and to unravel mechanisms of long-term action of AEDs relevant in neuropsychiatric disorders.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1752-0509-3-11","type":"journal-article","created":{"date-parts":[[2009,1,21]],"date-time":"2009-01-21T07:13:32Z","timestamp":1232522012000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A Drosophila systems model of pentylenetetrazole induced locomotor plasticity responsive to antiepileptic drugs"],"prefix":"10.1186","volume":"3","author":[{"given":"Farhan","family":"Mohammad","sequence":"first","affiliation":[]},{"given":"Priyanka","family":"Singh","sequence":"additional","affiliation":[]},{"given":"Abhay","family":"Sharma","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2009,1,21]]},"reference":[{"key":"279_CR1","doi-asserted-by":"publisher","first-page":"re12","DOI":"10.1126\/stke.3562006re12","volume":"356","author":"JO McNamara","year":"2006","unstructured":"McNamara JO, Huang YZ, Leonard AS: Molecular signaling mechanisms underlying epileptogenesis. Sci STKE. 2006, 356: re12-10.1126\/stke.3562006re12.","journal-title":"Sci STKE"},{"key":"279_CR2","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1038\/nn1791","volume":"9","author":"M Garriga-Canut","year":"2006","unstructured":"Garriga-Canut M, Schoenike B, Qazi R, Bergendahl K, Daley TJ, Pfender RM, Morrison JF, Ockuly J, Stafstrom C, Sutula T, Roopra A: 2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Nat Neurosci. 2006, 9: 1382-1387. 10.1038\/nn1791","journal-title":"Nat Neurosci"},{"key":"279_CR3","doi-asserted-by":"publisher","first-page":"11083","DOI":"10.1523\/JNEUROSCI.2766-06.2006","volume":"26","author":"JA Gorter","year":"2006","unstructured":"Gorter JA, van Vliet EA, Aronica E, Breit T, Rauwerda H, Lopes da Silva FH, Wadman WJ: Potential new antiepileptogenic targets indicated by microarray analysis in a rat model for temporal lobe epilepsy. J Neurosci. 2006, 26: 11083-11110. 10.1523\/JNEUROSCI.2766-06.2006","journal-title":"J Neurosci"},{"key":"279_CR4","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/nm1074","volume":"10","author":"MA Rogawski","year":"2004","unstructured":"Rogawski MA, Loscher W: The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions. Nat Med. 2004, 10: 685-692. 10.1038\/nm1074","journal-title":"Nat Med"},{"key":"279_CR5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.2165\/00023210-200822010-00003","volume":"22","author":"LC Johannessen","year":"2008","unstructured":"Johannessen LC: Antiepileptic drugs in non-epileptic disorders: relations between mechanisms of action and clinical efficacy. CNS Drugs. 2008, 22: 27-47. 10.2165\/00023210-200822010-00003","journal-title":"CNS Drugs"},{"key":"279_CR6","doi-asserted-by":"crossref","first-page":"77","DOI":"10.31887\/DCNS.2008.10.1\/hcrgrunze","volume":"10","author":"HC Grunze","year":"2008","unstructured":"Grunze HC: The effectiveness of anticonvulsants in psychiatric disorders. Dialogues Clin Neurosci. 2008, 10: 77-89.","journal-title":"Dialogues Clin Neurosci"},{"key":"279_CR7","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1192\/bjp.bp.107.046664","volume":"192","author":"SJ Adams","year":"2008","unstructured":"Adams SJ, O'Brien TJ, Lloyd J, Kilpatrick CJ, Salzberg MR, Velakoulis D: Neuropsychiatric morbidity in focal epilepsy. Br J Psychiatry. 2008, 192: 464-469. 10.1192\/bjp.bp.107.046664","journal-title":"Br J Psychiatry"},{"key":"279_CR8","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/0014-4886(69)90128-9","volume":"25","author":"GV Goddard","year":"1969","unstructured":"Goddard GV, McIntyre DC, Leech CK: A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol. 1969, 25: 295-330. 10.1016\/0014-4886(69)90128-9","journal-title":"Exp Neurol"},{"key":"279_CR9","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1093\/brain\/awf203","volume":"125","author":"MC Walker","year":"2002","unstructured":"Walker MC, White HS, Sander JW: Disease modification in partial epilepsy. Brain. 2002, 125: 1937-1950. 10.1093\/brain\/awf203","journal-title":"Brain"},{"key":"279_CR10","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.yebeh.2003.12.004","volume":"5","author":"H Husum","year":"2004","unstructured":"Husum H, Bolwig TG, Sanchez C, Mathe AA, Hansen SL: Levetiracetam prevents changes in levels of brain derived neurotrophic factor and neuropeptide Y mRNA and Y1- and Y5-like receptors in the hippocampus of rats undergoing amygdale kindling: implications for antiepileptogenic and mood-stabilizing properties. Epilepsy Behav. 2004, 5: 204-215. 10.1016\/j.yebeh.2003.12.004","journal-title":"Epilepsy Behav"},{"key":"279_CR11","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.neuropharm.2005.09.017","volume":"50","author":"F Jia","year":"2006","unstructured":"Jia F, Kato M, Dai H, Xu A, Okuda T, Sakurai E, Okamura N, Lovenberg TW, Barbier A, Carruthers NI, Iinuma K, Yanai K: Effects of histamine H(3) antagonists and donepexil on learning and mnemonic deficits induced in weanling mice. Neuropharmacology. 2006, 50: 404-411. 10.1016\/j.neuropharm.2005.09.017","journal-title":"Neuropharmacology"},{"key":"279_CR12","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.neulet.2005.09.021","volume":"392","author":"T Pavlova","year":"2006","unstructured":"Pavlova T, Stepanichev M, Gulyaeva N: Pentylenetetrazole kindling induces neuronal cyclin B1 expression in rat hippocampus. Neurosci Lett. 2006, 392: 154-158. 10.1016\/j.neulet.2005.09.021","journal-title":"Neurosci Lett"},{"key":"279_CR13","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1016\/j.seizure.2007.04.013","volume":"16","author":"T De Smedt","year":"2007","unstructured":"De Smedt T, De Rouck S, Raedt R, Wyckhuys T, Waterschoot L, De Herdt V, Van Dycke A, Tahry RE, Vonck K, Boon P: Serial day rapid kindling is an effective tool in screening the anti-epileptic properties of topiramate. Seizure. 2007, 16: 620-626. 10.1016\/j.seizure.2007.04.013","journal-title":"Seizure"},{"key":"279_CR14","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s00221-005-0081-3","volume":"168","author":"A Becker","year":"2006","unstructured":"Becker A, Schmitz M, Grecksch G: Kindling modifies morphine, cocaine and ethanol place preference. Exp Brain Res. 2006, 168: 33-40. 10.1007\/s00221-005-0081-3","journal-title":"Exp Brain Res"},{"key":"279_CR15","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.yebeh.2005.08.019","volume":"7","author":"F Mortazavi","year":"2005","unstructured":"Mortazavi F, Ericson M, Story D, Hulce VD, Dunbar GL: Spatial learning deficits and emotional impairements in pentylenetetrazole-kindled rats. Epilepsy Behav. 2005, 7: 629-638. 10.1016\/j.yebeh.2005.08.019","journal-title":"Epilepsy Behav"},{"key":"279_CR16","first-page":"321","volume":"27","author":"P Bob","year":"2006","unstructured":"Bob P, Glaslova K, Susta M, Jasova D, Raboch J: Traumatic dissociation, epileptic-like phenomena, and schizophrenia. Neuro Endocrinol Lett. 2006, 27: 321-326.","journal-title":"Neuro Endocrinol Lett"},{"key":"279_CR17","doi-asserted-by":"publisher","first-page":"8295","DOI":"10.1523\/JNEUROSCI.1986-05.2006","volume":"26","author":"KK Cole-Edwards","year":"2006","unstructured":"Cole-Edwards KK, Musto AE, Bazan NG: c-Jun N-terminal kinase activation responses induced by hippocampal kindling are mediated by reactive astrocytes. J Neurosci. 2006, 26: 8295-8304. 10.1523\/JNEUROSCI.1986-05.2006","journal-title":"J Neurosci"},{"key":"279_CR18","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1534\/genetics.105.043174","volume":"170","author":"E Glasscock","year":"2005","unstructured":"Glasscock E, Singhania A, Tanouye MA: The mei-P26 gene encodes an RBCC-NHL protein that regulates seizure susceptibility in Drosophila. Genetics. 2005, 170: 1677-1689. 10.1534\/genetics.105.043174","journal-title":"Genetics"},{"key":"279_CR19","doi-asserted-by":"publisher","first-page":"8943","DOI":"10.1523\/JNEUROSCI.4998-05.2006","volume":"30","author":"DS Hekmat-Scafe","year":"2006","unstructured":"Hekmat-Scafe DS, Lundy MY, Ranga R, Tanouye MA: Mutations in the K+\/Cl- cotransporter gene kazachoc (kcc) increase seizure susceptibility in Drosophila. J Neurosci. 2006, 30: 8943-8954. 10.1523\/JNEUROSCI.4998-05.2006.","journal-title":"J Neurosci"},{"key":"279_CR20","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1534\/genetics.106.057463","volume":"173","author":"T Fergestad","year":"2006","unstructured":"Fergestad T, Bostwick B, Ganetzky B: Metabolic disruption in Drosophila bang-sensitive seizure mutants. Genetics. 2006, 173: 1357-1364. 10.1534\/genetics.106.057463","journal-title":"Genetics"},{"key":"279_CR21","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.1111\/j.1460-9568.2006.05075.x","volume":"24","author":"GE Stilwell","year":"2006","unstructured":"Stilwell GE, Saraswati S, Littleton JT, Chouinard SW: Development of a Drosophila seizure model for in vivo high-throughput drug screening. Eur J Neurosci. 2006, 24: 2211-2222. 10.1111\/j.1460-9568.2006.05075.x","journal-title":"Eur J Neurosci"},{"key":"279_CR22","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1097\/WCO.0b013e328042bae0","volume":"20","author":"SC Baraban","year":"2007","unstructured":"Baraban SC: Emerging epilepsy models: insights from mice, flies, worms and fish. Curr Opin Neurol. 2007, 20: 164-168. 10.1097\/WCO.0b013e328042bae0","journal-title":"Curr Opin Neurol"},{"key":"279_CR23","doi-asserted-by":"publisher","first-page":"2927","DOI":"10.1523\/JNEUROSCI.3944-06.2007","volume":"27","author":"J Song","year":"2007","unstructured":"Song J, Hu J, Tanouye M: Seizure suppression by top1 mutations in Drosophila. J Neurosci. 2007, 27: 2927-2937. 10.1523\/JNEUROSCI.3944-06.2007","journal-title":"J Neurosci"},{"key":"279_CR24","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/S0006-8993(02)03431-5","volume":"958","author":"D Kuebler","year":"2002","unstructured":"Kuebler D, Tanouye M: Anticonvulsant valproate reduces seizure-susceptibility in mutant Drosophila. Brain Res. 2002, 958: 36-42. 10.1016\/S0006-8993(02)03431-5","journal-title":"Brain Res"},{"key":"279_CR25","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1002\/neu.10297","volume":"58","author":"ER Reynolds","year":"2004","unstructured":"Reynolds ER, Stauffer EA, Feeney L, Rojahn E, Jacobs B, McKeener C: Treatments with the antiepileptic drugs phenytoin and gabapentin ameliorates seizure and paralysis of Drosophila bang-sensitive mutants. J Neurobiol. 2004, 58: 503-513. 10.1002\/neu.10297","journal-title":"J Neurobiol"},{"key":"279_CR26","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.brainres.2004.05.111","volume":"1020","author":"JS Tan","year":"2004","unstructured":"Tan JS, Lin F, Tanouye MA: Potassium bromide, an anticonvulsant, is effective at alleviating seizures in the Drosophila bang-sensitive mutant bang-senseless. Brain Res. 2004, 1020: 45-52. 10.1016\/j.brainres.2004.05.111","journal-title":"Brain Res"},{"key":"279_CR27","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1534\/genetics.104.036558","volume":"169","author":"DS Hekmat-Scafe","year":"2005","unstructured":"Hekmat-Scafe DS, Dang KN, Tanouye MA: Seizure suppression by gain-of-function escargot mutations. Genetics. 2005, 169: 1477-1493. 10.1534\/genetics.104.036558","journal-title":"Genetics"},{"key":"279_CR28","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1038\/nbt1017","volume":"22","author":"EC Butcher","year":"2004","unstructured":"Butcher EC, Berg EL, Kunkel EJ: Systems biology in drug discovery. Nat Biotechnol. 2004, 22: 1253-1259. 10.1038\/nbt1017","journal-title":"Nat Biotechnol"},{"key":"279_CR29","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/nrm1857","volume":"7","author":"AR Joyce","year":"2006","unstructured":"Joyce AR, Palsson BO: The model organism as a system: integrating 'omics' data sets. Nat Rev Mol Cell Biol. 2006, 7: 198-210. 10.1038\/nrm1857","journal-title":"Nat Rev Mol Cell Biol"},{"key":"279_CR30","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/ng2049","volume":"39","author":"VR Chintapalli","year":"2007","unstructured":"Chintapalli VR, Wang J, Dow JAT: Using FlyAtlas to identify better Drosophila melanogaster models of human diseases. Nat Genet. 2007, 39: 715-720. 10.1038\/ng2049","journal-title":"Nat Genet"},{"key":"279_CR31","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/s00221-008-1295-y","volume":"187","author":"PA de Oliveira","year":"2008","unstructured":"de Oliveira PA, Lino FL, Cappelari SE, da Silva Brum LF, Picada JN, Patr\u00edcia Pereira P: Effects of gamma-decanolactone on seizures induced by PTZ-kindling in mice. Exp Brain Res. 2008, 187: 161-166. 10.1007\/s00221-008-1295-y","journal-title":"Exp Brain Res"},{"key":"279_CR32","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.1016\/S0028-3908(00)00050-2","volume":"39","author":"G De Sarro","year":"2000","unstructured":"De Sarro G, Palma E, Costa N, Marra R, Gratteri S, De Sarro A, Rotiroti D: Effects of compounds acting on GABAB receptors in the pentylenetetrazole kindling model of epilepsy in mice. Neuropharmacol. 2000, 39: 2147-2161. 10.1016\/S0028-3908(00)00050-2.","journal-title":"Neuropharmacol"},{"key":"279_CR33","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/S0022-3565(24)37308-2","volume":"284","author":"M Beekman","year":"1998","unstructured":"Beekman M, Ungard JT, Gasior M, Carter RB, Dijkstra D, Goldberg SR, Witkin JM: Reversal of Behavioral Effects of Pentylenetetrazole by the Neuroactive Steroid Ganaxolone. J Pharmacol Exp Ther. 1998, 284: 868-877.","journal-title":"J Pharmacol Exp Ther"},{"key":"279_CR34","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/S0091-3057(01)00612-8","volume":"70","author":"H Franke","year":"2001","unstructured":"Franke H, Kittner H: Morphological alterations of neurons and astrocytes and changes in emotional behavior in pentylenetetrazol-kindled rats. Pharmacol Biochem Behav. 2001, 70: 291-303. 10.1016\/S0091-3057(01)00612-8","journal-title":"Pharmacol Biochem Behav"},{"key":"279_CR35","doi-asserted-by":"publisher","first-page":"4518","DOI":"10.1523\/JNEUROSCI.0542-04.2004","volume":"24","author":"P Wang","year":"2004","unstructured":"Wang P, Saraswati S, Guan Z, Watkins CJ, Wurtman RJ, Littleton JT: A Drosophila Temperature-Sensitive Seizure Mutant in Phosphoglycerate Kinase disrupts ATP Generation and Alters Synaptic Function. J Neurosci. 2004, 24: 4518-4529. 10.1523\/JNEUROSCI.0542-04.2004","journal-title":"J Neurosci"},{"key":"279_CR36","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.beproc.2004.04.003","volume":"67","author":"JR Martin","year":"2004","unstructured":"Martin JR: A portrait of locomotor behaviour in Drosophila determined by a video-tracking paradigm. Behav Processes. 2004, 67: 207-219. 10.1016\/j.beproc.2004.04.003","journal-title":"Behav Processes"},{"key":"279_CR37","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/sj.mp.4001742","volume":"11","author":"HY Chang","year":"2006","unstructured":"Chang HY, Grygoruk A, Brooks ES, Ackerson LC, Maidment NT, Bainton RJ, Krantz DE: Overexpression of the Drosophila vesicular monoamine transporter increases motor activity and courtship but decreases the behavioral response to cocaine. Mol Psychiatry. 2006, 11: 99-113. 10.1038\/sj.mp.4001742","journal-title":"Mol Psychiatry"},{"key":"279_CR38","doi-asserted-by":"publisher","first-page":"5116","DOI":"10.1073\/pnas.091062498","volume":"98","author":"VG Tusher","year":"2001","unstructured":"Tusher VG, Tibshirani R, Chu G: Significance analysis of microarrays applied to the ionizing radiation. Proc Natl Acad Sci. 2001, 98: 5116-5121. 10.1073\/pnas.091062498","journal-title":"Proc Natl Acad Sci"},{"key":"279_CR39","doi-asserted-by":"publisher","first-page":"R101","DOI":"10.1186\/gb-2004-5-12-r101","volume":"5","author":"D Martin","year":"2004","unstructured":"Martin D, Brun C, Remy E, Mouren P, Thieffry D, Jacq B: GOToolBox: functional investigation of gene datasets based on Gene Ontology. Genome Biol. 2004, 5: R101- 10.1186\/gb-2004-5-12-r101","journal-title":"Genome Biol"},{"key":"279_CR40","doi-asserted-by":"publisher","first-page":"P3","DOI":"10.1186\/gb-2003-4-5-p3","volume":"4","author":"GJr Dennis","year":"2003","unstructured":"Dennis GJr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA: DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003, 4: P3- 10.1186\/gb-2003-4-5-p3","journal-title":"Genome Biol"},{"key":"279_CR41","doi-asserted-by":"publisher","first-page":"2118","DOI":"10.1101\/gr.771603","volume":"13","author":"H Mi","year":"2003","unstructured":"Mi H, Vandergriff J, Campbell M, Narechania A, Majoros W, Lewis S, Thomas PD, Ashburner M: Assessment of genome-wide protein function classification for Drosophila melanogaster. Genome Res. 2003, 13: 2118-2128. 10.1101\/gr.771603","journal-title":"Genome Res"},{"key":"279_CR42","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/S0920-1211(02)00073-6","volume":"50","author":"W Loscher","year":"2002","unstructured":"Loscher W: Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy. Epilepsy Res. 2002, 50: 105-123. 10.1016\/S0920-1211(02)00073-6","journal-title":"Epilepsy Res"},{"issue":"7","key":"279_CR43","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1111\/j.1528-1167.2008.01594.x","volume":"49","author":"LV Vinogradova","year":"2008","unstructured":"Vinogradova LV, van Rijn CM: Anticonvulsive and antiepileptogenic effects of levetiracetam in the audiogenic kindling model. Epilepsia. 2008, 49 (7): 1160-1168. 10.1111\/j.1528-1167.2008.01594.x","journal-title":"Epilepsia"},{"key":"279_CR44","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.2165\/00003495-200161080-00002","volume":"61","author":"NR Temkin","year":"2001","unstructured":"Temkin NR, Jarell AD, Anderson GD: Antiepileptogenic agents: how close are we?. Drugs. 2001, 61: 1045-1055. 10.2165\/00003495-200161080-00002","journal-title":"Drugs"},{"key":"279_CR45","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1111\/j.1528-1167.2005.29604.x","volume":"46","author":"C Ji-qun","year":"2005","unstructured":"Ji-qun C, Ishihara K, Nagayama T, Serikawa T, Sasa M: Long-lasting antiepileptic effects of levetiracetam against epileptic seizures in the spontaneously epileptic rat (SER): differentiation of levetiracetam from conventional antiepileptic drugs. Epilepsia. 2005, 46: 1362-1370. 10.1111\/j.1528-1167.2005.29604.x","journal-title":"Epilepsia"},{"key":"279_CR46","doi-asserted-by":"publisher","first-page":"research0008.1","DOI":"10.1186\/gb-2001-2-3-research0008","volume":"2","author":"KL Posey","year":"2001","unstructured":"Posey KL, Jones LB, Cerda R, Bajaj M, Huynh T, Hardin PE, Hardin SH, et al.: Survey of transcripts in the adult Drosophila brain. Genome Biol. 2001, 2: research0008.1-research0008.16. 10.1186\/gb-2001-2-3-research0008.","journal-title":"Genome Biol"},{"key":"279_CR47","doi-asserted-by":"publisher","first-page":"D535","DOI":"10.1093\/nar\/gkj109","volume":"34","author":"C Stark","year":"2006","unstructured":"Stark C, Breitkreutz B-J, Reguly T, Boucher L, Breitkreutz A, Tyers M: BioGRID: a general repository for interaction datasets. Nucleic Acids Res. 2006, 34: D535-D539. 10.1093\/nar\/gkj109","journal-title":"Nucleic Acids Res"},{"key":"279_CR48","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1111\/j.1528-1167.2007.01055.x","volume":"48","author":"CL Busceti","year":"2007","unstructured":"Busceti CL, Biagioni F, Aronica E, Riozzi B, Storto M, Battaglia G, Giogi FS, Gradini R, Fornai F, Caricasole A, Nicoletti F, Bruno V: Induction of the Wnt inhibitor, Dickkopf-1, is associated with neurodegeneration related to temporal lobe epilepsy. Epilepsia. 2007, 48: 694-705. 10.1111\/j.1528-1167.2007.01055.x","journal-title":"Epilepsia"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-3-11.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T02:50:33Z","timestamp":1738896633000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-3-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,1,21]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["279"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-3-11","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,1,21]]},"assertion":[{"value":"18 September 2008","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2009","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2009","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"11"}}