{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:12:03Z","timestamp":1790291523745,"version":"4.1.0"},"reference-count":137,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071042"],"award-info":[{"award-number":["82071042"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["20ZR1442300"],"award-info":[{"award-number":["20ZR1442300"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>In the past several decades, bilirubin has attracted great attention for central nervous system (CNS) toxicity in some pathological conditions with severely elevated bilirubin levels. CNS function relies on the structural and functional integrity of neural circuits, which are large and complex electrochemical networks. Neural circuits develop from the proliferation and differentiation of neural stem cells, followed by dendritic and axonal arborization, myelination, and synapse formation. The circuits are immature, but robustly developing, during the neonatal period. It is at the same time that physiological or pathological jaundice occurs. The present review comprehensively discusses the effects of bilirubin on the development and electrical activity of neural circuits to provide a systematic understanding of the underlying mechanisms of bilirubin-induced acute neurotoxicity and chronic neurodevelopmental disorders.<\/jats:p>","DOI":"10.3389\/fncel.2023.1136250","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T04:39:12Z","timestamp":1679373552000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Effects of bilirubin on the development and electrical activity of neural circuits"],"prefix":"10.3389","volume":"17","author":[{"given":"Cuiping","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuefan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqi","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankai","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.mcn.2019.03.003","article-title":"Modulation of Ca(v)2.3 channels by unconjugated bilirubin (UCB) - Candidate mechanism for UCB-induced neuromodulation and neurotoxicity.","volume":"96","author":"Albanna","year":"2019","journal-title":"Mol. Cell Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1111\/cns.12791","article-title":"Unconjugated bilirubin modulates neuronal signaling only in wild-type mice, but not after ablation of the R-type\/Ca(v) 2.3 voltage-gated calcium channel.","volume":"24","author":"Albanna","year":"2018","journal-title":"CNS Neurosci. Ther."},{"key":"B3","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1159\/000244119","article-title":"Dose-effect relationship of bilirubin on striatal synaptosomes in rats.","volume":"66","author":"Amato","year":"1994","journal-title":"Biol. Neonate"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-4009","article-title":"Chronic auditory toxicity in late preterm and term infants with significant hyperbilirubinemia.","volume":"140","author":"Amin","year":"2017","journal-title":"Pediatrics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/s41390-018-0216-4","article-title":"Developmental influence of unconjugated hyperbilirubinemia and neurobehavioral disorders.","volume":"85","author":"Amin","year":"2019","journal-title":"Pediatr. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1007\/s10803-010-1169-6","article-title":"Is neonatal jaundice associated with Autism Spectrum Disorders: a systematic review.","volume":"41","author":"Amin","year":"2011","journal-title":"J. Autism Dev. Disord."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108719","article-title":"Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration.","volume":"196","author":"Andersen","year":"2021","journal-title":"Neuropharmacology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1124\/mol.115.098228","article-title":"Reduced myelination and increased glia reactivity resulting from severe neonatal hyperbilirubinemia.","volume":"89","author":"Barateiro","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1007\/s12035-013-8530-7","article-title":"Rat cerebellar slice cultures exposed to bilirubin evidence reactive gliosis, excitotoxicity and impaired myelinogenesis that is prevented by AMPA and TNF-alpha inhibitors.","volume":"49","author":"Barateiro","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1007\/s12035-012-8364-8","article-title":"Unconjugated bilirubin restricts oligodendrocyte differentiation and axonal myelination.","volume":"47","author":"Barateiro","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/s12017-012-8187-9","article-title":"ER stress, mitochondrial dysfunction and calpain\/JNK activation are involved in oligodendrocyte precursor cell death by unconjugated bilirubin.","volume":"14","author":"Barateiro","year":"2012","journal-title":"Neuromol. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1177\/1073858412438697","article-title":"The GABA excitatory\/inhibitory shift in brain maturation and neurological disorders.","volume":"18","author":"Ben-Ari","year":"2012","journal-title":"Neuroscientist"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/858929","article-title":"Perinatal cerebellar injury in human and animal models.","volume":"2012","author":"Biran","year":"2012","journal-title":"Neurol Res. Int."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1242\/dmm.016535","article-title":"Age-dependent pattern of cerebellar susceptibility to bilirubin neurotoxicity in vivo in mice.","volume":"7","author":"Bortolussi","year":"2014","journal-title":"Dis. Model Mech."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198504000-01373","article-title":"1349 in vitro effect of bilirubin on dopamine synthesis in adult rat brain synaptosomes.","volume":"19","author":"Brann","year":"1985","journal-title":"Pediatr. Res."},{"key":"B16","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1542\/peds.73.4.431","article-title":"Effect of acidosis on bilirubin deposition in rat brain.","volume":"73","author":"Bratlid","year":"1984","journal-title":"Pediatrics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.siny.2014.12.002","article-title":"Bilirubin-induced neural impairment: a special focus on myelination, age-related windows of susceptibility and associated co-morbidities.","volume":"20","author":"Brites","year":"2015","journal-title":"Semin. Fetal Neonatal Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.brainres.2004.07.063","article-title":"A link between hyperbilirubinemia, oxidative stress and injury to neocortical synaptosomes.","volume":"1026","author":"Brito","year":"2004","journal-title":"Brain Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.cca.2006.06.012","article-title":"Bilirubin toxicity to human erythrocytes: a review.","volume":"374","author":"Brito","year":"2006","journal-title":"Clin. Chim. Acta"},{"key":"B20","doi-asserted-by":"publisher","first-page":"4031","DOI":"10.1242\/dev.106559","article-title":"Development of the cerebellum: simple steps to make a \u2018little brain\u2019.","volume":"141","author":"Butts","year":"2014","journal-title":"Development"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2020.101845","article-title":"White matter injury and neurodevelopmental disabilities: a cross-disease (dis)connection.","volume":"193","author":"Cainelli","year":"2020","journal-title":"Prog. Neurobiol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10101532","article-title":"The effects of bilirubin and lumirubin on the differentiation of human pluripotent cell-derived neural stem cells.","volume":"10","author":"Capkov\u00e1","year":"2021","journal-title":"Antioxidants"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a003947","article-title":"Voltage-gated calcium channels.","volume":"3","author":"Catterall","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005876","article-title":"Unconjugated bilirubin exposure impairs hippocampal long-term synaptic plasticity.","volume":"4","author":"Chang","year":"2009","journal-title":"PLoS One"},{"key":"B25","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1212\/WNL.0000000000000228","article-title":"Differential distribution of voltage-gated ion channels in cortical neurons: implications for epilepsy.","volume":"82","author":"Child","year":"2014","journal-title":"Neurology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1161\/ATVBAHA.119.313055","article-title":"Causal associations between serum bilirubin levels and decreased stroke risk: a two-sample mendelian randomization study.","volume":"40","author":"Choi","year":"2020","journal-title":"Arterioscl. Thromb. Vasc. Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"E191","DOI":"10.1152\/ajpendo.00405.2020","article-title":"Bilirubin as a metabolic hormone: the physiological relevance of low levels.","volume":"320","author":"Creeden","year":"2021","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19071869","article-title":"PPARs and energy metabolism adaptation during neurogenesis and neuronal maturation.","volume":"19","author":"D\u2019Angelo","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1007\/s00431-018-3245-4","article-title":"Changes in bilirubin in infants with hypoxic-ischemic encephalopathy.","volume":"177","author":"Dani","year":"2018","journal-title":"Eur. J. Pediatr."},{"key":"B30","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1159\/000494101","article-title":"Neurotoxicity of unconjugated bilirubin in mature and immature rat organotypic hippocampal slice cultures.","volume":"115","author":"Dani","year":"2019","journal-title":"Neonatology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1002\/pmic.200900579","article-title":"A proteomic approach to the bilirubin-induced toxicity in neuronal cells reveals a protective function of DJ-1 protein.","volume":"10","author":"Deganuto","year":"2010","journal-title":"Proteomics"},{"key":"B32","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.conb.2017.12.013","article-title":"Neural circuit dysfunction in mouse models of neurodevelopmental disorders.","volume":"48","author":"Del Pino","year":"2018","journal-title":"Curr. Opin. Neurobiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1056\/NEJM200102223440807","article-title":"Neonatal hyperbilirubinemia.","volume":"344","author":"Dennery","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/mp.2013.65","article-title":"Microbiota is essential for social development in the mouse.","volume":"19","author":"Desbonnet","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"B35","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1073\/pnas.1010529108","article-title":"Normal gut microbiota modulates brain development and behavior.","volume":"108","author":"Diaz Heijtz","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101263","article-title":"Oxidative stress and regulated cell death in Parkinson\u2019s disease.","volume":"67","author":"Dionisio","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1111\/j.1749-6632.1999.tb07991.x","article-title":"Neuroprotective action of bilirubin against oxidative stress in primary hippocampal cultures.","volume":"890","author":"Dor\u00e9","year":"1999","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.nbd.2005.03.001","article-title":"Bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cells.","volume":"20","author":"Falcao","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"B39","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s00401-006-0078-4","article-title":"Bilirubin-induced immunostimulant effects and toxicity vary with neural cell type and maturation state.","volume":"112","author":"Falcao","year":"2006","journal-title":"Acta Neuropathol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1002\/jnr.21227","article-title":"Apoptosis and impairment of neurite network by short exposure of immature rat cortical neurons to unconjugated bilirubin increase with cell differentiation and are additionally enhanced by an inflammatory stimulus.","volume":"85","author":"Falcao","year":"2007","journal-title":"J. Neurosci. Res."},{"key":"B41","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/B978-0-12-814411-4.00006-8","article-title":"Spike timing\u2013dependent plasticity","author":"Feldman","year":"2020","journal-title":"Neural Circuit and Cognitive Development"},{"key":"B42","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1002\/dneu.20727","article-title":"Bilirubin as a determinant for altered neurogenesis, neuritogenesis, and synaptogenesis.","volume":"69","author":"Fernandes","year":"2009","journal-title":"Dev. Neurobiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2803","DOI":"10.2174\/0929867321666140303143455","article-title":"Neuroprotective properties of peroxisome proliferator-activated receptor alpha (PPARalpha) and its lipid ligands.","volume":"21","author":"Fidaleo","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1002\/hep.29599","article-title":"Systemic regulation of bilirubin homeostasis: potential benefits of hyperbilirubinemia.","volume":"67","author":"Fujiwara","year":"2018","journal-title":"Hepatology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/j.molmed.2016.07.004","article-title":"A novel perspective on the biology of bilirubin in health and disease.","volume":"22","author":"Gazzin","year":"2016","journal-title":"Trends Mol. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1152\/physiolgenomics.00028.2019","article-title":"RNA sequencing in human HepG2 hepatocytes reveals PPAR-alpha mediates transcriptome responsiveness of bilirubin.","volume":"51","author":"Gordon","year":"2019","journal-title":"Physiol. Genomics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"9804","DOI":"10.1074\/jbc.RA120.013700","article-title":"Bilirubin remodels murine white adipose tissue by reshaping mitochondrial activity and the coregulator profile of peroxisome proliferator-activated receptor alpha.","volume":"295","author":"Gordon","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B48","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1006\/exnr.2000.7518","article-title":"Bilirubin induces apoptosis via activation of NMDA receptors in developing rat brain neurons.","volume":"166","author":"Grojean","year":"2000","journal-title":"Exp. Neurol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1055\/s-0040-1718879","article-title":"The relationship between serum total bilirubin and severity of hypoxic injury in neonatal hypoxic-ischemic encephalopathy.","volume":"39","author":"Haga","year":"2022","journal-title":"Am. J. Perinatol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1111\/cns.12355","article-title":"Riluzole is a promising pharmacological inhibitor of bilirubin-induced excitotoxicity in the ventral cochlear nucleus.","volume":"21","author":"Han","year":"2015","journal-title":"CNS Neurosci. Ther."},{"key":"B51","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1124\/pharmrev.120.000131","article-title":"Structure, function, and pharmacology of glutamate receptor ion channels.","volume":"73","author":"Hansen","year":"2021","journal-title":"Pharmacol. Rev."},{"key":"B52","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1203\/00006450-198802000-00018","article-title":"Bilirubin decreases phosphorylation of synapsin I, a synaptic vesicle-associated neuronal phosphoprotein, in intact synaptosomes from rat cerebral cortex.","volume":"23","author":"Hansen","year":"","journal-title":"Pediatr. Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1203\/00006450-198805000-00002","article-title":"Short-term exposure to bilirubin reduces synaptic activation in rat transverse hippocampal slices.","volume":"23","author":"Hansen","year":"","journal-title":"Pediatr. Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1023\/a:1020775312214","article-title":"Bilirubin inhibits Ca2+-dependent release of norepinephrine from permeabilized nerve terminals.","volume":"24","author":"Hansen","year":"1999","journal-title":"Neurochem. Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1203\/00006450-199606000-00023","article-title":"Bilirubin has widespread inhibitory effects on protein phosphorylation.","volume":"39","author":"Hansen","year":"1996","journal-title":"Pediatr. Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1203\/00006450-199711000-00011","article-title":"Modulation of the effect of bilirubin on protein phosphorylation by lysine-containing peptides.","volume":"42","author":"Hansen","year":"1997","journal-title":"Pediatr. Res."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1152\/physrev.00004.2019","article-title":"Molecular physiology and pathophysiology of bilirubin handling by the blood, liver, intestine, and brain in the newborn.","volume":"100","author":"Hansen","year":"2020","journal-title":"Physiol. Rev."},{"key":"B58","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1146\/annurev-neuro-072116-031005","article-title":"Inhibitory plasticity: balance, control, and codependence.","volume":"40","author":"Hennequin","year":"2017","journal-title":"Annu. Rev. Neurosci."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24917-8","article-title":"Low bilirubin levels indicate a high risk of cerebral deep white matter lesions in apparently healthy subjects.","volume":"8","author":"Higuchi","year":"2018","journal-title":"Sci. Rep."},{"key":"B60","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1203\/00006450-199612000-00005","article-title":"The in vivo effect of bilirubin on the N-methyl-D-aspartate receptor\/ion channel complex in the brains of newborn piglets.","volume":"40","author":"Hoffman","year":"1996","journal-title":"Pediatr. Res."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.294","article-title":"Adult neurobehavioral outcome of hyperbilirubinemia in full term neonates-a 30 year prospective follow-up study.","volume":"2","author":"Hokkanen","year":"2014","journal-title":"PeerJ"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-014-0087-5","article-title":"Ex vivo (1)H nuclear magnetic resonance spectroscopy reveals systematic alterations in cerebral metabolites as the key pathogenetic mechanism of bilirubin encephalopathy.","volume":"7","author":"Hu","year":"2014","journal-title":"Mol. Brain"},{"key":"B63","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1542\/peds.2007-0967","article-title":"Outcomes in a population of healthy term and near-term infants with serum bilirubin levels of >or=325 micromol\/L (>or=19 mg\/dL) who were born in Nova Scotia, Canada, between 1994 and 2000.","volume":"122","author":"Jangaard","year":"2008","journal-title":"Pediatrics"},{"key":"B64","doi-asserted-by":"publisher","first-page":"92","DOI":"10.20517\/2347-8659.2019.14","article-title":"Bilirubin and inflammation in neurodegenerative and other neurological diseases.","volume":"7","author":"Jayanti","year":"2020","journal-title":"Neuroimmunol. Neuroinflamm."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126223","article-title":"Bilirubin: a promising therapy for Parkinson\u2019s disease.","volume":"22","author":"Jayanti","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1097\/CM9.0000000000001300","article-title":"Association between serum bilirubin concentration and Parkinson\u2019s disease: a meta-analysis.","volume":"134","author":"Jin","year":"2020","journal-title":"Chin. Med. J."},{"key":"B67","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.pediatrneurol.2012.06.019","article-title":"Hyperbilirubinemia: subcortical mechanisms of cognitive and behavioral dysfunction.","volume":"48","author":"Koziol","year":"2013","journal-title":"Pediatr. Neurol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1146\/annurev.neuro.051508.135600","article-title":"The glial nature of embryonic and adult neural stem cells.","volume":"32","author":"Kriegstein","year":"2009","journal-title":"Annu. Rev. Neurosci."},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax1337","article-title":"Bilirubin enhances the activity of ASIC channels to exacerbate neurotoxicity in neonatal hyperbilirubinemia in mice.","volume":"12","author":"Lai","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3390\/life11111168","article-title":"PPARalpha modulation-based therapy in central nervous system diseases.","volume":"11","author":"Lee","year":"2021","journal-title":"Life"},{"key":"B71","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1097\/RLU.0000000000002749","article-title":"Bilirubin-related differential striatal [18F] FP-CIT uptake in Parkinson Disease.","volume":"44","author":"Lee","year":"2019","journal-title":"Clin. Nucl. Med."},{"key":"B72","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/s41563-019-0462-9","article-title":"Hyaluronic acid-bilirubin nanomedicine for targeted modulation of dysregulated intestinal barrier, microbiome and immune responses in colitis.","volume":"19","author":"Lee","year":"2020","journal-title":"Nat. Mater."},{"key":"B73","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.brainres.2010.06.022","article-title":"Protein kinase A and C signaling induces bilirubin potentiation of GABA\/glycinergic synaptic transmission in rat ventral cochlear nucleus neurons.","volume":"1348","author":"Li","year":"2010","journal-title":"Brain Res."},{"key":"B74","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.tox.2011.03.010","article-title":"Bilirubin enhances neuronal excitability by increasing glutamatergic transmission in the rat lateral superior olive.","volume":"284","author":"Li","year":"2011","journal-title":"Toxicology"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2022.136747","article-title":"NAD+ attenuates bilirubin-induced augmentation of voltage-gated calcium currents in neurons of the ventral cochlear nucleus.","volume":"784","author":"Liang","year":"2022","journal-title":"Neurosci. Lett."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00275-9","article-title":"Bilirubin augments Ca(2+) load of developing bushy neurons by targeting specific subtype of voltage-gated calcium channels.","volume":"7","author":"Liang","year":"","journal-title":"Sci. Rep."},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00021","article-title":"NAD+ attenuates bilirubin-induced hyperexcitation in the ventral cochlear nucleus by inhibiting excitatory neurotransmission and neuronal excitability.","volume":"11","author":"Liang","year":"","journal-title":"Front. Cell Neurosci."},{"key":"B78","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.4049\/jimmunol.181.3.1887","article-title":"Bilirubin possesses powerful immunomodulatory activity and suppresses experimental autoimmune encephalomyelitis.","volume":"181","author":"Liu","year":"2008","journal-title":"J. Immunol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1007\/s11011-013-9409-z","article-title":"Association of serum bilirubin and uric acid levels changes during neuroinflammation in patients with initial and relapsed demyelination attacks.","volume":"28","author":"Ljubisavljevic","year":"2013","journal-title":"Metab. Brain Dis."},{"key":"B80","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.parkreldis.2019.01.012","article-title":"Increased bilirubin levels in Parkinson\u2019s disease.","volume":"63","author":"Macias-Garcia","year":"2019","journal-title":"Parkinsonism Relat. Disord."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1093\/brain\/awr286","article-title":"Tau elevations in the brain extracellular space correlate with reduced amyloid-\u03b2 levels and predict adverse clinical outcomes after severe traumatic brain injury.","volume":"135","author":"Magnoni","year":"2012","journal-title":"Brain"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3390\/cells8020184","article-title":"Astrocytes maintain glutamate homeostasis in the CNS by controlling the balance between glutamate uptake and release.","volume":"8","author":"Mahmoud","year":"2019","journal-title":"Cells"},{"key":"B83","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1542\/peds.2010-0052","article-title":"Neonatal jaundice, autism, and other disorders of psychological development.","volume":"126","author":"Maimburg","year":"2010","journal-title":"Pediatrics"},{"key":"B84","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1523\/JNEUROSCI.4445-12.2013","article-title":"Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth.","volume":"33","author":"Malik","year":"2013","journal-title":"J. Neurosci."},{"key":"B85","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1111\/j.1471-4159.1986.tb04510.x","article-title":"Effect of bilirubin on the membrane potential of rat brain synaptosomes.","volume":"47","author":"Mayor","year":"1986","journal-title":"J. Neurochem."},{"key":"B86","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1006\/exnr.1997.6762","article-title":"Role of glutamate receptor-mediated excitotoxicity in bilirubin-induced brain injury in the Gunn rat model.","volume":"150","author":"McDonald","year":"1998","journal-title":"Exp. Neurol."},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.44116","article-title":"Identification of a bilirubin receptor that may mediate a component of cholestatic itch.","volume":"8","author":"Meixiong","year":"2019","journal-title":"Elife"},{"key":"B88","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1111\/ene.12688","article-title":"Increased bilirubin levels in de novo Parkinson\u2019s disease.","volume":"22","author":"Moccia","year":"2015","journal-title":"Eur. J. Neurol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/S0140-6736(11)61577-8","article-title":"Long-term neurodevelopmental outcomes after intrauterine and neonatal insults: a systematic review.","volume":"379","author":"Mwaniki","year":"2012","journal-title":"Lancet"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003507","article-title":"A product of heme catabolism modulates bacterial function and survival.","volume":"9","author":"Nobles","year":"2013","journal-title":"PLoS Pathog."},{"key":"B91","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1080\/14756366.2021.2020773","article-title":"Pharmaceutical strategies for preventing toxicity and promoting antioxidant and anti-inflammatory actions of bilirubin.","volume":"37","author":"Nocentini","year":"2022","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"B92","first-page":"1571","article-title":"1H MR spectroscopic characteristics of kernicterus: a possible metabolic signature.","volume":"26","author":"Oakden","year":"2005","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/BF00712990","article-title":"Interactions of bilirubin with isolated presynaptic nerve terminals: functional effects on the uptake and release of neurotransmitters.","volume":"13","author":"Ochoa","year":"1993","journal-title":"Cell Mol. Neurobiol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.pediatrneurol.2008.07.004","article-title":"Tau and S100B proteins as biochemical markers of bilirubin-induced neurotoxicity in term neonates.","volume":"39","author":"Okumus","year":"2008","journal-title":"Pediatr. Neurol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1161\/CIRCULATIONAHA.104.528802","article-title":"Bilirubin: a natural inhibitor of vascular smooth muscle cell proliferation.","volume":"112","author":"Ollinger","year":"2005","journal-title":"Circulation"},{"key":"B96","doi-asserted-by":"publisher","first-page":"3078","DOI":"10.4161\/cc.6.24.5022","article-title":"Bilirubin inhibits tumor cell growth via activation of ERK.","volume":"6","author":"Ollinger","year":"2007","journal-title":"Cell Cycle"},{"key":"B97","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1016\/S2352-4642(18)30139-1","article-title":"Neonatal hyperbilirubinaemia: a global perspective.","volume":"2","author":"Olusanya","year":"2018","journal-title":"Lancet Child Adolesc. Health"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1016\/j.jocn.2011.02.023","article-title":"Serum bilirubin concentrations and multiple sclerosis.","volume":"18","author":"Peng","year":"2011","journal-title":"J. Clin. Neurosci."},{"key":"B99","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1006\/abbi.1998.0814","article-title":"Activation of the Ah receptor signal transduction pathway by bilirubin and biliverdin.","volume":"357","author":"Phelan","year":"1998","journal-title":"Arch. Biochem. Biophys."},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3390\/cells11172647","article-title":"Bilirubin-induced neurological damage: current and emerging iPSC-derived brain organoid models.","volume":"11","author":"Pranty","year":"2022","journal-title":"Cells"},{"key":"B101","author":"Purves","year":"2012","journal-title":"Neuroscience"},{"key":"B102","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1007\/s00204-020-02659-9","article-title":"Bilirubin disrupts calcium homeostasis in neonatal hippocampal neurons: a new pathway of neurotoxicity.","volume":"94","author":"Rauti","year":"2020","journal-title":"Arch. Toxicol."},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079073","article-title":"Alterations in the cell cycle in the cerebellum of hyperbilirubinemic Gunn rat: a possible link with apoptosis?","volume":"8","author":"Robert","year":"2013","journal-title":"PLoS One"},{"key":"B104","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1203\/00006450-199809000-00008","article-title":"Bilirubin inhibits transport of neurotransmitters in synaptic vesicles.","volume":"44","author":"Roseth","year":"1998","journal-title":"Pediatr. Res."},{"key":"B105","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.conb.2017.12.005","article-title":"Neural stem cells in neuropsychiatric disorders.","volume":"48","author":"Sacco","year":"2018","journal-title":"Curr. Opin. Neurobiol."},{"key":"B106","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.clp.2013.10.007","article-title":"Neurogenesis and maturation in neonatal brain injury.","volume":"41","author":"Salmaso","year":"2014","journal-title":"Clin. Perinatol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"5171","DOI":"10.1073\/pnas.0813132106","article-title":"Bilirubin and glutathione have complementary antioxidant and cytoprotective roles.","volume":"106","author":"Sedlak","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B108","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1053\/j.semperi.2011.02.011","article-title":"Auditory impairment in infants at risk for bilirubin-induced neurologic dysfunction.","volume":"35","author":"Shapiro","year":"2011","journal-title":"Semin. Perinatol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1159\/000103743","article-title":"NMDA channel antagonist MK-801 does not protect against bilirubin neurotoxicity.","volume":"92","author":"Shapiro","year":"2007","journal-title":"Neonatology"},{"key":"B110","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.neures.2006.02.015","article-title":"Bilirubin potentiates inhibitory synaptic transmission in lateral superior olive neurons of the rat.","volume":"55","author":"Shi","year":"2006","journal-title":"Neurosci. Res."},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1979-1","article-title":"Ca(2+)-dependent recruitment of voltage-gated sodium channels underlies bilirubin-induced overexcitation and neurotoxicity.","volume":"10","author":"Shi","year":"2019","journal-title":"Cell Death Dis."},{"key":"B112","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1006\/bbrc.1999.1646","article-title":"Inhibition of glutamate uptake by unconjugated bilirubin in cultured cortical rat astrocytes: role of concentration and pH.","volume":"265","author":"Silva","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B113","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.1016\/j.neuropharm.2012.02.002","article-title":"Neuritic growth impairment and cell death by unconjugated bilirubin is mediated by NO and glutamate, modulated by microglia, and prevented by glycoursodeoxycholic acid and interleukin-10.","volume":"62","author":"Silva","year":"2012","journal-title":"Neuropharmacology"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020479","article-title":"Oligodendrocytes: myelination and axonal support.","volume":"8","author":"Simons","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B115","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1038\/s41380-019-0426-0","article-title":"Excitation-inhibition balance as a framework for investigating mechanisms in neuropsychiatric disorders.","volume":"24","author":"Sohal","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"B116","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.ijdevneu.2012.02.001","article-title":"Differences in developmental changes in GABAergic response between bushy and stellate cells in the rat anteroventral cochlear nucleus.","volume":"30","author":"Song","year":"2012","journal-title":"Int. J. Dev. Neurosci."},{"key":"B117","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/nature05300","article-title":"Electrical activity in early neuronal development.","volume":"444","author":"Spitzer","year":"2006","journal-title":"Nature"},{"key":"B118","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1126\/science.3029864","article-title":"Bilirubin is an antioxidant of possible physiological importance.","volume":"235","author":"Stocker","year":"1987","journal-title":"Science"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202103052","article-title":"The cell biology of synapse formation.","volume":"220","author":"Sudhof","year":"2021","journal-title":"J. Cell Biol."},{"key":"B120","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1113\/jphysiol.2004.063388","article-title":"Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice.","volume":"558","author":"Sudo","year":"2004","journal-title":"J. Physiol."},{"key":"B121","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/npp.2009.115","article-title":"Normal development of brain circuits.","volume":"35","author":"Tau","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"B122","doi-asserted-by":"publisher","first-page":"5483","DOI":"10.1007\/s12035-018-1440-y","article-title":"Bilirubin and ischemic stroke: rendering the current paradigm to better understand the protective effects of bilirubin.","volume":"56","author":"Thakkar","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228650","article-title":"The anti-inflammatory role of bilirubin on \u201cTwo-Hit\u201d sepsis animal model.","volume":"21","author":"Tran","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B124","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/0091-3057(93)90252-o","article-title":"Na+,K(+)-ATPase and acetylcholinesterase activities: changes in postnatally developing rat brain induced by bilirubin.","volume":"45","author":"Tsakiris","year":"1993","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B125","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1016\/j.chembiol.2019.07.006","article-title":"Bilirubin links heme metabolism to neuroprotection by scavenging superoxide.","volume":"26","author":"Vasavda","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"B126","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/S0021-9258(19)57294-5","article-title":"Interaction of bilirubin with the synaptosomal plasma membrane.","volume":"263","author":"Vazquez","year":"1988","journal-title":"J. Biol. Chem."},{"key":"B127","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1016\/j.biotechadv.2018.08.002","article-title":"Neural stem cell differentiation into mature neurons: mechanisms of regulation and biotechnological applications.","volume":"36","author":"Vieira","year":"2018","journal-title":"Biotechnol. Adv."},{"key":"B128","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1002\/med.21660","article-title":"Bilirubin as a signaling molecule.","volume":"40","author":"Vitek","year":"2020","journal-title":"Med. Res. Rev."},{"key":"B129","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1056\/NEJMcibr2013250","article-title":"Bilirubin, intestinal integrity, the microbiome, and inflammation.","volume":"383","author":"Vitek","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B130","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/s0006-8993(00)02676-7","article-title":"Bilirubin does not modulate ionotropic glutamate receptors or glutamate transporters.","volume":"879","author":"Warr","year":"2000","journal-title":"Brain Res."},{"key":"B131","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1385\/NMM:8:4:513","article-title":"Kernicterus and the molecular mechanisms of bilirubin-induced CNS injury in newborns.","volume":"8","author":"Watchko","year":"2006","journal-title":"Neuromol. Med."},{"key":"B132","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.clp.2016.01.007","article-title":"Bilirubin-induced neurotoxicity in the preterm neonate.","volume":"43","author":"Watchko","year":"2016","journal-title":"Clin. Perinatol."},{"key":"B133","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1023\/a:1006900111744","article-title":"The blood-brain barrier and bilirubin encephalopathy.","volume":"20","author":"Wennberg","year":"2000","journal-title":"Cell Mol. Neurobiol."},{"key":"B134","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1001\/jamapediatrics.2014.3036","article-title":"Risk for cerebral palsy in infants with total serum bilirubin levels at or above the exchange transfusion threshold: a population-based study.","volume":"169","author":"Wu","year":"2015","journal-title":"JAMA Pediatr."},{"key":"B135","doi-asserted-by":"publisher","first-page":"200","DOI":"10.5114\/aoms.2019.88625","article-title":"The effects of hyperbilirubinaemia on synaptic plasticity in the dentate gyrus region of the rat hippocampus in vivo.","volume":"16","author":"Yang","year":"2020","journal-title":"Arch. Med. Sci."},{"key":"B136","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.toxlet.2015.10.008","article-title":"The role of gamma-aminobutyric acid\/glycinergic synaptic transmission in mediating bilirubin-induced hyperexcitation in developing auditory neurons.","volume":"240","author":"Yin","year":"2016","journal-title":"Toxicol. Lett."},{"key":"B137","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1203\/01.PDR.0000061563.63230.86","article-title":"The effects of bilirubin on evoked potentials and long-term potentiation in rat hippocampus in vivo.","volume":"53","author":"Zhang","year":"2003","journal-title":"Pediatr. Res."}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2023.1136250\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T04:39:18Z","timestamp":1679373558000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2023.1136250\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,21]]},"references-count":137,"alternative-id":["10.3389\/fncel.2023.1136250"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2023.1136250","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,21]]},"article-number":"1136250"}}