{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T04:12:18Z","timestamp":1785125538016,"version":"3.55.0"},"reference-count":56,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T00:00:00Z","timestamp":1685836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Preludium 11","award":["2016\/21\/N\/NZ4\/03658"],"award-info":[{"award-number":["2016\/21\/N\/NZ4\/03658"]}]},{"name":"Preludium 11","award":["189220"],"award-info":[{"award-number":["189220"]}]},{"name":"Preludium 11","award":["GW\/PB\/59\/2021"],"award-info":[{"award-number":["GW\/PB\/59\/2021"]}]},{"DOI":"10.13039\/501100001711","name":"SNFS Grant","doi-asserted-by":"publisher","award":["2016\/21\/N\/NZ4\/03658"],"award-info":[{"award-number":["2016\/21\/N\/NZ4\/03658"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"SNFS Grant","doi-asserted-by":"publisher","award":["189220"],"award-info":[{"award-number":["189220"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"SNFS Grant","doi-asserted-by":"publisher","award":["GW\/PB\/59\/2021"],"award-info":[{"award-number":["GW\/PB\/59\/2021"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical University of Lublin","award":["2016\/21\/N\/NZ4\/03658"],"award-info":[{"award-number":["2016\/21\/N\/NZ4\/03658"]}]},{"name":"Medical University of Lublin","award":["189220"],"award-info":[{"award-number":["189220"]}]},{"name":"Medical University of Lublin","award":["GW\/PB\/59\/2021"],"award-info":[{"award-number":["GW\/PB\/59\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Zebrafish (Danio rerio) assays provide a versatile pharmacological platform to test compounds on a wide range of behaviors in a whole organism. A major challenge lies in the lack of knowledge about the bioavailability and pharmacodynamic effects of bioactive compounds in this model organism. Here, we employed a combined methodology of LC-ESI-MS\/MS analytics and targeted metabolomics with behavioral experiments to evaluate the anticonvulsant and potentially toxic effects of the angular dihydropyranocoumarin pteryxin (PTX) in comparison to the antiepileptic drug sodium valproate (VPN) in zebrafish larvae. PTX occurs in different Apiaceae plants traditionally used in Europe to treat epilepsy but has not been investigated so far. To compare potency and efficacy, the uptake of PTX and VPN into zebrafish larvae was quantified as larvae whole-body concentrations together with amino acids and neurotransmitters as proxy pharmacodynamic readout. The convulsant agent pentylenetetrazole (PTZ) acutely reduced the levels of most metabolites, including acetylcholine and serotonin. Conversely, PTX strongly reduced neutral essential amino acids in a LAT1 (SLCA5)-independent manner, but, similarly to VPN specifically increased the levels of serotonin, acetylcholine, and choline, but also ethanolamine. PTX dose and time-dependent manner inhibited PTZ-induced seizure-like movements resulting in a ~70% efficacy after 1 h at 20 \u00b5M (the equivalent of 4.28 \u00b1 0.28 \u00b5g\/g in larvae whole-body). VPN treated for 1 h with 5 mM (the equivalent of 18.17 \u00b1 0.40 \u00b5g\/g in larvae whole-body) showed a ~80% efficacy. Unexpectedly, PTX (1\u201320 \u00b5M) showed significantly higher bioavailability than VPN (0.1\u20135 mM) in immersed zebrafish larvae, possibly because VPN in the medium dissociated partially to the readily bioavailable valproic acid. The anticonvulsive effect of PTX was confirmed by local field potential (LFP) recordings. Noteworthy, both substances specifically increased and restored whole-body acetylcholine, choline, and serotonin levels in control and PTZ-treated zebrafish larvae, indicative of vagus nerve stimulation (VNS), which is an adjunctive therapeutic strategy to treat refractory epilepsy in humans. Our study demonstrates the utility of targeted metabolomics in zebrafish assays and shows that VPN and PTX pharmacologically act on the autonomous nervous system by activating parasympathetic neurotransmitters.<\/jats:p>","DOI":"10.3390\/cells12111540","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T01:53:25Z","timestamp":1685930005000},"page":"1540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pharmacometabolic Effects of Pteryxin and Valproate on Pentylenetetrazole-Induced Seizures in Zebrafish Reveal Vagus Nerve Stimulation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6601-8295","authenticated-orcid":false,"given":"Adrianna","family":"Skiba","sequence":"first","affiliation":[{"name":"Department of Chemistry of Natural Products, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9666-7560","authenticated-orcid":false,"given":"Daniele","family":"Pellegata","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Morozova","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Kozio\u0142","sequence":"additional","affiliation":[{"name":"Department of Chemistry of Natural Products, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Budzy\u0144ska","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Behavioral Studies, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon Ming-Yuen","family":"Lee","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 519020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrg","family":"Gertsch","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9313-5929","authenticated-orcid":false,"given":"Krystyna","family":"Skalicka-Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Department of Chemistry of Natural Products, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/toxsci\/kfy044","article-title":"Making Waves: New Developments in Toxicology with the Zebrafish","volume":"163","author":"Horzmann","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.1007\/s00216-014-7929-y","article-title":"A Quantitative HPLC-MS\/MS Method for Studying Internal Concentrations and Toxicokinetics of 34 Polar Analytes in Zebrafish (Danio Rerio) Embryos","volume":"406","author":"Brox","year":"2014","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"881933","DOI":"10.3389\/fnmol.2022.881933","article-title":"Connectivity Mapping Using a Novel Sv2a Loss-of-Function Zebrafish Epilepsy Model as a Powerful Strategy for Anti-Epileptic Drug Discovery","volume":"15","author":"Zhang","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.tips.2013.12.002","article-title":"Zebrafish as an Emerging Model for Studying Complex Brain Disorders","volume":"35","author":"Kalueff","year":"2014","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Basnet, R.M., Zizioli, D., Taweedet, S., Finazzi, D., and Memo, M. (2019). Zebrafish Larvae as a Behavioral Model in Neuropharmacology. Biomedicines, 7.","DOI":"10.3390\/biomedicines7010023"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1163\/1568539X-00003020","article-title":"Zebrafish Embryos and Larvae in Behavioural Assays","volume":"149","author":"Ahmad","year":"2012","journal-title":"Behaviour"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.phytol.2018.12.002","article-title":"Efficient Extraction and Isolation of Skimmianine from New Caledonian Plant Medicosma Leratii and Evaluation of Its Effects on Apoptosis, Necrosis, and Autophagy","volume":"30","author":"Luca","year":"2019","journal-title":"Phytochem. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.brainresbull.2020.09.024","article-title":"Zebrafish and Mouse Models for Anxiety Evaluation\u2014A Comparative Study with Xanthotoxin as a Model Compound","volume":"165","author":"Michalak","year":"2020","journal-title":"Brain Res. Bull."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/978-3-319-30654-4_5","article-title":"Identifying Novel Cancer Therapies Using Chemical Genetics and Zebrafish","volume":"916","author":"Dang","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.talanta.2017.06.075","article-title":"Development of a Sensitive and Quantitative UHPLC-MS\/MS Method to Study the Whole-Body Uptake of Pharmaceuticals in Zebrafish","volume":"174","author":"Kislyuk","year":"2017","journal-title":"Talanta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10159","DOI":"10.1021\/acs.est.0c02068","article-title":"Yolk Sac of Zebrafish Embryos as Backpack for Chemicals?","volume":"54","author":"Halbach","year":"2020","journal-title":"Environ. Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.neuint.2017.11.011","article-title":"Methylated Flavonoids as Anti-Seizure Agents: Naringenin 4\u2032,7-Dimethyl Ether Attenuates Epileptic Seizures in Zebrafish and Mouse Models","volume":"112","author":"Copmans","year":"2018","journal-title":"Neurochem. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12229","DOI":"10.1038\/s41598-021-91612-6","article-title":"Spatiotemporal Imaging and Pharmacokinetics of Fluorescent Compounds in Zebrafish Eleuthero-Embryos after Different Routes of Administration","volume":"11","author":"Guarin","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Afrikanova, T., Serruys, A.S.K., Buenafe, O.E.M., Clinckers, R., Smolders, I., de Witte, P.A.M., Crawford, A.D., and Esguerra, C.V. (2013). Validation of the Zebrafish Pentylenetetrazol Seizure Model: Locomotor versus Electrographic Responses to Antiepileptic Drugs. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054166"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e1900017","DOI":"10.1002\/cbdv.201900017","article-title":"Profiling Auspicious Butyrylcholinesterase Inhibitory Activity of Two Herbal Molecules: Hyperforin and Hyuganin C","volume":"16","author":"Orhan","year":"2019","journal-title":"Chem. Biodivers."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"378","DOI":"10.3389\/fnmol.2018.00378","article-title":"Syntaxin 1B Mediates Berberine\u2019s Roles in Epilepsy-like Behavior in a Pentylenetetrazole-Induced Seizure Zebrafish Model","volume":"11","author":"Zheng","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Koziol, E., J\u00f3\u017awiak, K., Budzy\u0144ska, B., de Witte, P.A.M., Copmans, D., and Skalicka-wo\u017aniak, K. (2021). Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111420"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2012.06.010","article-title":"Epilepsy in the Renaissance: A Survey of Remedies from 16th and 17th Century German Herbals","volume":"143","author":"Adams","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ejphar.2009.02.022","article-title":"Osthole Suppresses Seizures in the Mouse Maximal Electroshock Seizure Model","volume":"607","author":"Luszczki","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","first-page":"259","article-title":"High-Performance Counter-Current Chromatography Isolation and Initial Neuroactivity Characterization of Furanocoumarin Derivatives from Peucedanum Alsaticum L (Apiaceae)","volume":"15","author":"Deniz","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"926","DOI":"10.2174\/1570159X17666181227165722","article-title":"Valproic Acid and Epilepsy: From Molecular Mechanisms to Clinical Evidences","volume":"17","author":"Romoli","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.biopsych.2004.06.012","article-title":"Lithium and Valproic Acid Treatment Effects on Brain Chemistry in Bipolar Disorder","volume":"56","author":"Friedman","year":"2004","journal-title":"Biol. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S1059-1311(95)80003-4","article-title":"Mechanisms of Action of Antiepileptic Drugs","volume":"4","author":"Davies","year":"1995","journal-title":"Seizure"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10258","DOI":"10.1038\/s41598-022-12937-4","article-title":"Histone Deacetylase 2 Inhibitor Valproic Acid Attenuates Bisphenol A-Induced Liver Pathology in Male Mice","volume":"12","author":"Alshibani","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s00204-020-02928-7","article-title":"Neurotoxic Effects in Zebrafish Embryos by Valproic Acid and Nine of Its Analogues: The Fish-Mouse Connection?","volume":"95","author":"Brotzmann","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"114051","DOI":"10.1016\/j.biopha.2022.114051","article-title":"Valproate, Divalproex, Valpromide: Are the Differences in Indications Justified?","volume":"158","author":"Delage","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"232","DOI":"10.5414\/CP203961","article-title":"De Comparative Bioavailability Study with Two Sodium Valproate Tablet Formulations Administered under Fasting Conditions in Healthy Subjects","volume":"60","author":"Mendes","year":"2022","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"173","DOI":"10.21037\/atm.2018.04.25","article-title":"Characterization of the Locomotor Activities of Zebrafish Larvae under the Influence of Various Neuroactive Drugs","volume":"6","author":"Li","year":"2018","journal-title":"Ann. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"108916","DOI":"10.1016\/j.jneumeth.2020.108916","article-title":"Development and Validation of Chemical Kindling in Adult Zebrafish: A Simple and Improved Chronic Model for Screening of Antiepileptic Agents","volume":"346","author":"Kumari","year":"2020","journal-title":"J. Neurosci. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/FTD.0000000000000405","article-title":"Monitoring Protein-Unbound Valproic Acid Serum Concentrations in Clinical Practice","volume":"39","author":"Wallenburg","year":"2017","journal-title":"Ther. Drug Monit."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"103632","DOI":"10.1016\/j.mod.2020.103632","article-title":"The Anti-Epileptic Drug Valproic Acid Causes Malformations in the Developing Craniofacial Skeleton of Zebrafish Larvae","volume":"163","author":"Gebuijs","year":"2020","journal-title":"Mech. Dev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/bmc.1733","article-title":"Study on Pharmacokinetics and Tissue Distribution of Pteryxin in Mice by Ultra-Pressure Liquid Chromatography with Tandem Mass Spectrometry","volume":"26","author":"Wang","year":"2012","journal-title":"Biomed. Chromatogr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.brainresbull.2007.10.043","article-title":"Functional and Developmental Analysis of the Blood-Brain Barrier in Zebrafish","volume":"75","author":"Jeong","year":"2008","journal-title":"Brain Res. Bull."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fleming, A., Diekmann, H., and Goldsmith, P. (2013). Functional Characterisation of the Maturation of the Blood-Brain Barrier in Larval Zebrafish. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077548"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Dalangin, R., Kim, A., and Campbell, R.E. (2020). The Role of Amino Acids in Neurotransmission and Fluorescent Tools for Their Detection. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176197"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1021\/acschemneuro.9b00610","article-title":"Zebrafish-Based Screening of Antiseizure Plants Used in Traditional Chinese Medicine: Magnolia officinalis Extract and Its Constituents Magnolol and Honokiol Exhibit Potent Anticonvulsant Activity in a Therapy-Resistant Epilepsy Model","volume":"11","author":"Li","year":"2020","journal-title":"ACS Chem Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s40263-019-00650-2","article-title":"Branched-Chain Amino Acids and Seizures: A Systematic Review of the Literature","volume":"33","author":"Gruenbaum","year":"2019","journal-title":"CNS Drugs"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2105586","DOI":"10.1002\/advs.202105586","article-title":"Exosomes-Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth","volume":"9","author":"Fan","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1007\/s11064-022-03634-9","article-title":"Electroacupuncture Promotes Autophagy by Regulating the AKT\/MTOR Signaling Pathway in Temporal Lobe Epilepsy","volume":"47","author":"Gao","year":"2022","journal-title":"Neurochem. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"102294","DOI":"10.1016\/j.npep.2022.102294","article-title":"Protective Effect of N-Acetyl Cysteine on the Mitochondrial Dynamic Imbalance in Temporal Lobe Epilepsy: Possible Role of MTOR","volume":"96","author":"Mohammadi","year":"2022","journal-title":"Neuropeptides"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e21526","DOI":"10.1096\/fj.202001798RR","article-title":"L-Leucine Promotes Axonal Outgrowth and Regeneration via MTOR Activation","volume":"35","author":"Ma","year":"2021","journal-title":"FASEB J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1007\/s10695-021-00984-z","article-title":"The Zebrafish Cationic Amino Acid Transporter\/Glycoprotein-Associated Family: Sequence and Spatiotemporal Distribution during Development of the Transport System b(0,+) (Slc3a1\/Slc7a9)","volume":"47","author":"Ellingsen","year":"2021","journal-title":"Fish Physiol. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1124\/mol.61.3.695","article-title":"Increased Sensitivity to Nicotine-Induced Seizures in Mice Expressing the L250T Alpha 7 Nicotinic Acetylcholine Receptor Mutation","volume":"61","author":"Broide","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.4103\/2152-7806.91610","article-title":"Vagus Nerve Stimulation for Epilepsy: A Review of the Peripheral Mechanisms","volume":"3","author":"Krahl","year":"2012","journal-title":"Surg. Neurol. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"696543","DOI":"10.3389\/fmedt.2021.696543","article-title":"Evolution of the Vagus Nerve Stimulation (VNS) Therapy System Technology for Drug-Resistant Epilepsy","volume":"3","author":"Afra","year":"2021","journal-title":"Front. Med. Technol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.brs.2011.04.005","article-title":"Novel Attempts to Optimize Vagus Nerve Stimulation Parameters on Serotonin Neuronal Firing Activity in the Rat Brain","volume":"5","author":"Manta","year":"2012","journal-title":"Brain Stimul."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/epi4.12580","article-title":"Serotonin Receptors in Epilepsy: Novel Treatment Targets?","volume":"7","author":"Sourbron","year":"2022","journal-title":"Epilepsia Open"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1021\/acschemneuro.5b00342","article-title":"Serotonergic Modulation as Effective Treatment for Dravet Syndrome in a Zebrafish Mutant Model","volume":"7","author":"Sourbron","year":"2016","journal-title":"ACS Chem. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Kecsk\u00e9s, A., Copmans, D., Langlois, M., Crawford, A.D., Ceulemans, B., Lagae, L., de Witte, P.A.M., and Esguerra, C. (2015). V Pharmacological Characterization of an Antisense Knockdown Zebrafish Model of Dravet Syndrome: Inhibition of Epileptic Seizures by the Serotonin Agonist Fenfluramine. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125898"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S1474-4422(04)00850-6","article-title":"The Vagus Nerve\u2013A Common Route for Epilepsy Therapies?","volume":"3","author":"Cullingford","year":"2004","journal-title":"Lancet. Neurol."},{"key":"ref_51","first-page":"64","article-title":"Closed-Loop Neural Stimulation for Pentylenetetrazole-Induced Seizures in Zebrafish","volume":"6","author":"Pineda","year":"2013","journal-title":"Dis. Model. Mech."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"dmm049550","DOI":"10.1242\/dmm.049550","article-title":"A Multidimensional Metabolomics Workflow to Image Biodistribution and Evaluate Pharmacodynamics in Adult Zebrafish","volume":"15","author":"Jackstadt","year":"2022","journal-title":"Dis. Model. Mech."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/cne.21705","article-title":"Development of Enteric and Vagal Innervation of the Zebrafish (Danio Rerio) Gut","volume":"508","author":"Olsson","year":"2008","journal-title":"J. Comp. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"629073","DOI":"10.3389\/fcell.2020.629073","article-title":"Zebrafish: A Model Organism for Studying Enteric Nervous System Development and Disease","volume":"8","author":"Kuil","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1210\/er.2018-00283","article-title":"Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule","volume":"40","author":"Yabut","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41421-021-00247-4","article-title":"Mechanism of substrate transport and inhibition of the human LAT1-4F2hc amino acid transporter","volume":"7","author":"Yan","year":"2021","journal-title":"Cell Discov."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/11\/1540\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:47:54Z","timestamp":1760125674000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/11\/1540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,4]]},"references-count":56,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["cells12111540"],"URL":"https:\/\/doi.org\/10.3390\/cells12111540","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,4]]}}}