Agmatine rescues autistic behaviors in the valproic acid-induced animal model of autism
Abstract
Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. Interestingly, our previous study involving the valproic acid animal model of autism (VPA animal model) has demonstrated excitatory-inhibitory imbalance (E/I imbalance) due to enhanced differentiation of glutamatergic neurons and reduced GABAergic neurons. Here, we investigated the potential of agmatine, an endogenous NMDA receptor antagonist, as a novel therapeutic candidate in ameliorating ASD symptoms by modulating E/I imbalance using the VPA animal model. We observed that a single treatment of agmatine rescued the impaired social behaviors as well as hyperactive and repetitive behaviors in the VPA animal model. We also observed that agmatine treatment rescued the overly activated ERK1/2 signaling in the prefrontal cortex and hippocampus of VPA animal models, possibly, by modulating over-excitability due to enhanced excitatory neural circuit. Taken together, our results have provided experimental evidence suggesting a possible therapeutic role of agmatine in ameliorating ASD-like symptoms in the VPA animal model of ASD.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
VPA administration during gestation leads to ASD-like behaviors, notably social deficits, in offspring.
“Accordingly, in rodents, VPA administration during gestation leads to ASD-like behaviors (notably social deficits) in offspring (Kim et al., 2017).”
From Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder (2019) · cites this paper as Kim et al., 2017
Cites
Model of autism: increased ratio of excitation/inhibition in key neural systems
Rubenstein, J. L. R., & Merzenich, M. M. (2003) · Genes, Brain and Behavior · doi:10.1034/j.1601-183x.2003.00037.x · Cited by 2,768 · see citing works
Neocortical excitation/inhibition balance in information processing and social dysfunction
Yizhar, O., Fenno, L. E., Prigge, M., Schneider, F., Davidson, T. J., O’Shea, D. J., Sohal, V. S., Goshen, I., Finkelstein, J., Paz, J. T., et al. (2011) · Nature · doi:10.1038/nature10360 · Cited by 2,454 · see citing works
MAPK cascade signalling and synaptic plasticity
Thomas, G. M., & Huganir, R. L. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1346 · Cited by 1,454 · see citing works
Bymaster, F. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(02)00346-9 · Cited by 1,123 · see citing works
Excitatory/Inhibitory Balance and Circuit Homeostasis in Autism Spectrum Disorders
Nelson, S. B., & Valakh, V. (2015) · Neuron · doi:10.1016/j.neuron.2015.07.033 · Cited by 1,001 · see citing works
Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Animal Model of Autism
Schneider, T., & Przewłocki, R. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300518 · Cited by 959 · see citing works
Chauhan, A., & Chauhan, V. (2006) · Pathophysiology · doi:10.1016/j.pathophys.2006.05.007 · Cited by 656 · see citing works
Assessment of Social Interaction Behaviors
Kaidanovich‐Beilin, O., Lipina, T. V., Vukobradovic, I., Roder, J., & Woodgett, J. R. (2011) · Journal of Visualized Experiments · doi:10.3791/2473 · Cited by 550 · see citing works
Valproic acid in pregnancy: how much are we endangering the embryo and fetus?
Ornoy, A. (2009) · Reproductive Toxicology · doi:10.1016/j.reprotox.2009.02.014 · Cited by 526 · see citing works
The Intense World Theory – A Unifying Theory of the Neurobiology of Autism
Markram, H., & Markram, H. (2010) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2010.00224 · Cited by 522 · see citing works
Characteristics of fetal anticonvulsant syndrome associated autistic disorder
Rasalam, A., Hailey, H., Williams, J., Moore, S., Turnpenny, P., Lloyd, D., & Dean, J. (2005) · Developmental Medicine & Child Neurology · doi:10.1017/s0012162205001076 · Cited by 456 · see citing works
In utero exposure to valproic acid and autism — A current review of clinical and animal studies
Roullet, F., Lai, J., & Foster, J. A. (2013) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2013.01.004 · Cited by 425 · see citing works
Fetal valproate syndrome and autism: additional evidence of an association
Williams, G., King, J. O., Cunningham, M. L., Stephan, M., Kerr, B. A., & Hersh, J. H. (2001) · Developmental Medicine & Child Neurology · doi:10.1017/s001216220100038x · Cited by 422 · see citing works
Is agmatine a novel neurotransmitter in brain?
Reis, D. J., & Regunathan, S. (2000) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01460-7 · Cited by 417 · see citing works
Mony, L., Kew, J. N. C., Gunthorpe, M. J., & Paoletti, P. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00304.x · Cited by 404 · see citing works
The intense world syndrome-an alternative hypothesis for autism
Markram, H. (2007) · Frontiers in Neuroscience · doi:10.3389/neuro.01.1.1.006.2007 · Cited by 394 · see citing works
Abnormal Fear Conditioning and Amygdala Processing in an Animal Model of Autism
Markram, H., Barkat, T. R., Mendola, D. L., Sandi, C., & Markram, H. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301453 · Cited by 382 · see citing works
Validating γ oscillations and delayed auditory responses as translational biomarkers of autism
Gandal, M. J., Edgar, J. C., Ehrlichman, R. S., Mehta, M., Roberts, T. P. L., & Siegel, S. J. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.031 · Cited by 314 · see citing works
Rinaldi, T., Kulangara, K., Antoniello, K., & Markram, H. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704391104 · Cited by 290 · see citing works
Fetal valproate syndrome and autism: additional evidence of an association
Williams, G. M., King, J. O., Cunningham, M. L., et al. (2001) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2001.tb00188.x · Cited by 290 · see citing works
The critical period of valproate exposure to induce autistic symptoms in Sprague–Dawley rats
Kim, K. C., Kim, P., Go, H. S., Choi, C. S., Yang, S., Cheong, J. H., Shin, C. Y., & Ko, K. H. (2010) · Toxicology Letters · doi:10.1016/j.toxlet.2010.12.018 · Cited by 285 · see citing works
Yang, X., & Reis, D. J. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37988-1 · Cited by 264 · see citing works
Agmatine: clinical applications after 100 years in translation
Piletz, J. E., Arıcıoğlu, F., Cheng, J., Fairbanks, C. A., Gilad, V. H., Haenisch, B., Halaris, A. E., Hong, S., Lee, J. E., Li, J., et al. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2013.05.017 · Cited by 248 · see citing works
Halaris, A. E., & Piletz, J. E. (2007) · CNS Drugs · doi:10.2165/00023210-200721110-00002 · Cited by 237 · see citing works
Osterweil, E. K., Chuang, S.-C., Chubykin, A. A., Sidorov, M., Bianchi, R., Wong, R. K. S., & Bear, M. F. (2013) · Neuron · doi:10.1016/j.neuron.2012.01.034 · Cited by 230 · see citing works
The neurobiology of repetitive behavior: Of mice…
Langen, M., Kas, M. J., Staal, W., van Engeland, H., & Durston, S. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.02.004 · Cited by 223 · see citing works
Progress toward treatments for synaptic defects in autism
Delorme, R., Ey, E., Toro, R., Leboyer, M., Gillberg, C., & Bourgeron, T. (2013) · Nature Medicine · doi:10.1038/nm.3193 · Cited by 218 · see citing works
Swanson, C. J., Perry, K. W., Koch-Krueger, S., Katner, J., Svensson, K. A., & Bymaster, F. P. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.11.022 · Cited by 214 · see citing works
Kim, K. C., Kim, P., Go, H. S., Choi, C. S., Park, J. H., Kim, H. J., Jeon, S. J., dela Pena, I. C., Han, S., Cheong, J. H., et al. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12147 · Cited by 212 · see citing works
Rinaldi, T. (2008) · Frontiers in Neural Circuits · doi:10.3389/neuro.04.004.2008 · Cited by 210 · see citing works
Ketamine Modulates Theta and Gamma Oscillations
Lazarewicz, M. T., Ehrlichman, R. S., Maxwell, C. R., Gandal, M. J., Finkel, L. H., & Siegel, S. J. (2009) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2009.21305 · Cited by 209 · see citing works
Gandal, M. J., Sisti, J., Klook, K., Ortinski, P. I., Leitman, V, Liang, Y., Thieu, T., Anderson, R., Pierce, R. C., Jonak, G., et al. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.69 · Cited by 204 · see citing works
Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses
Won, H., Mah, W., & Kim, E. (2013) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2013.00019 · Cited by 204 · see citing works
High nitric oxide production in autistic disorder: a possible role for interferon-γ
Sweeten, T. L., Posey, D. J., Shankar, S. S., & McDougle, C. J. (2003) · Biological Psychiatry · doi:10.1016/j.biopsych.2003.09.001 · Cited by 172 · see citing works
Kang, H. J., Choi, Y. S., Hong, S., Kim, K., Woo, R., Won, S. J., Kim, E. J., Jeon, H. K., Jo, S.-Y., Kim, T. K., et al. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4082-03.2004 · Cited by 137 · see citing works
Kim, K. C., Lee, D.-K., Go, H. S., Kim, P., Choi, C. S., Kim, J., Jeon, S. J., Song, M., & Shin, C. Y. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8535-2 · Cited by 135 · see citing works
Agmatinase Activity in Rat Brain: A Metabolic Pathway for the Degradation of Agmatine
Sastre, M., Regunathan, S., Galea, E., & Reis, D. J. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.67041761.x · Cited by 133 · see citing works
Kim, J., Seung, H., Kwon, K. J., Ko, M. J., Lee, E. J., Oh, H. A., Choi, C. S., Kim, K. C., Gonzales, E. L., You, J. S., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104927 · Cited by 117 · see citing works
Feng, Y., Piletz, J. E., & LeBlanc, M. H. (2002) · Pediatric Research · doi:10.1203/00006450-200210000-00023 · Cited by 114 · see citing works
Moore, C. M., Biederman, J., Wozniak, J. R., Mick, E. O., Aleardi, M., Wardrop, M., Dougherty, M., Harpold, T. L., Hammerness, P. G., Randall, E. T., et al. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.2.316 · Cited by 110 · see citing works
Russell, V. A. (2003) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2003.08.010 · Cited by 107 · see citing works
Selective blockade of spontaneous motor stereotypy via intrastriatal pharmacological manipulation
Presti, M. F., Mikes, H. M., & Lewis, M. H. (2003) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(02)01081-x · Cited by 94 · see citing works
Zhang, Y., Sun, Y., Wang, F., Wang, Z., Peng, Y., & Li, R. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0724-2 · Cited by 89 · see citing works
Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations
Ludolph, A. G., Udvardi, P. T., Schaz, U., Henes, C., Adolph, O., Weigt, H. U., Fegert, J. M., Boeckers, T. M., & Föhr, K. J. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00707.x · Cited by 82 · see citing works
Aberrant differentiation of glutamatergic cells in neocortex of mouse model for fragile X syndrome.
Tervonen, T. A., Louhivuori, V., Sun, X., Hokkanen, M.-E., Kratochwil, C. F., Zebryk, P., Castrén, E., & Castrén, M. L. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.10.010 · Cited by 82 · cited 1× · see citing works
“First, the Fragile X Syndromecausing knockdown or loss of FMRP (a syndromic ASD) in neural progenitor cells enhanced glutamatergic neuronal differentiation and, possibly, increased the glutamatergic neuronal number (Jeon et al., 2014; Tervonen et al., 2009).”
Kang, J., & Kim, E. (2015) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2015.00017 · Cited by 81 · see citing works
Feng, Y., LeBlanc, M. H., & Regunathan, S. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.08.008 · Cited by 81 · see citing works
Agmatine Crosses the Blood‐Brain Barrier
Piletz, J. E., May, P. J., Wang, G., & Zhu, H. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1304.007 · Cited by 75 · see citing works
Agmatine containing axon terminals in rat hippocampus form synapses on pyramidal cells
REIS, D. J., Yang, X., & Milner, T. A. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00466-2 · Cited by 74 · see citing works
Characterizing autism spectrum disorders by key biochemical pathways
Subramanian, M. P., Timmerman, C., Schwartz, J. L., Pham, D. L., & Meffert, M. K. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00313 · Cited by 71 · see citing works
Miller, E. M., Pomerleau, F., Huettl, P. F., Gerhardt, G. A., & Glaser, P. E. A. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3479-4 · Cited by 69 · see citing works
CARREY, N. J., MacMaster, F. P., Sparkes, S. J., Khan, S. C., & Kusumakar, V. (2002) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/104454602762599871 · Cited by 64 · see citing works
The role of the frontal cortex in the mouse in behavioral sensitization to amphetamine
Karler, R., Bedingfield, J. B., Thai, D. K., & Calder, L. D. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00221-7 · Cited by 60 · see citing works
The Clinician's Guide to Autism
Harrington, J. W., & Allen, K. (2014) · Pediatrics in Review · doi:10.1542/pir.35-2-62 · Cited by 58 · see citing works
Agmatine: A Novel Neurotransmitter?
Reis, D. J., & Regunathan, S. (1997) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60834-0 · Cited by 57 · see citing works
Anticonvulsive effect of agmatine in mice
Su, R., Wei, X.-L., Zheng, J., Liu, Y., Lu, X., & Li, J. (2003) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2003.11.016 · Cited by 56 · see citing works
Memantine in the Treatment of Executive Function Deficits in Adults With ADHD
Biederman, J., Fried, R., Tarko, L., Surman, C. B. H., Spencer, T., Pope, A., Grossman, R. A., McDermott, K., Woodworth, K., & Faraone, S. (2017) · Journal of Attention Disorders · doi:10.1177/1087054714538656 · Cited by 56 · see citing works
A role for polyamines in retinal ganglion cell excitotoxic death
Pernet, V., Bourgeois, P., & Polo, A. D. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04843.x · Cited by 56 · see citing works
The Role of the Striatum in the Mouse in Behavioral Sensitization to Amphetamine
Bedingfield, J. B. (1997) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(96)00331-0 · Cited by 50 · see citing works
Neuropharmacokinetic and Dynamic Studies of Agmatine (Decarboxylated Arginine)
Nguyen, H. O., Goracke‐Postle, C. J., KAMINSKI, L. L., Overland, A. C., MORGAN, A. D., & Fairbanks, C. A. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1304.009 · Cited by 43 · see citing works
Metabolism of agmatine into urea but not into nitric oxide in rat brain
Gilad, G. M., Wollam, Y., laina, A., Rabey, J. M., Chernihovsky, T., & Gilad, V. H. (1996) · Neuroreport · doi:10.1097/00001756-199607290-00007 · Cited by 41 · see citing works
Saunders, J. A., Gandal, M. J., Roberts, T. P. L., & Siegel, S. J. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.06.032 · Cited by 34 · see citing works
Release of tritiated agmatine from spinal synaptosomes
Goracke‐Postle, C. J., Nguyen, H. O., Stone, L. S., & Fairbanks, C. A. (2005) · Neuroreport · doi:10.1097/01.wnr.0000192739.38653.aa · Cited by 29 · see citing works
Jeon, S. J., Kim, J., Kim, K. C., Han, S. M., Go, H. S., Seo, J. E., Choi, C. S., Ryu, J. H., Shin, C. Y., & Song, M. (2013) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-013-0014-9 · Cited by 23 · see citing works
Overexpression of Telomerase Reverse Transcriptase Induces Autism-like Excitatory Phenotypes in Mice
Kim, K. C., Rhee, J., Park, J., Lee, D.-K., Choi, C. S., Kim, J., Lee, H., Song, M.-R., Yoo, H. J., Chung, C., et al. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9630-3 · Cited by 18 · see citing works
Putative Agmatinase Inhibitor for Hypoxic-Ischemic New Born Brain Damage
Piletz, J. E., Klenotich, S. J., Lee, K. S., Zhu, Q. L., Valente, E. J., Collins, M. A., Jones, V., Lee, S. N., & Yangzheng, F. (2013) · Neurotoxicity Research · doi:10.1007/s12640-013-9376-5 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Sgritta, M., Dooling, S. W., Buffington, S. A., Momin, E. N., Francis, M. B., Britton, R. A., & Costa-Mattioli, M. (2019) · Neuron · doi:10.1016/j.neuron.2018.11.018 · Cited by 865 · see citing works
Valproic Acid and Epilepsy: From Molecular Mechanisms to Clinical Evidences
Romoli, M., Mazzocchetti, P., D’Alonzo, R., Siliquini, S., Rinaldi, V. E., Verrotti, A., Calabresi, P., & Costa, C. (2018) · Current Neuropharmacology · doi:10.2174/1570159x17666181227165722 · Cited by 379 · see citing works
Wang, X., Wang, B., Wu, C., Wang, J., & Sun, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24031819 · Cited by 274 · see citing works
Oxidative Stress in Autism Spectrum Disorder—Current Progress of Mechanisms and Biomarkers
Liu, X., Jing, L., Zhang, H., Khan, N. U., Zhang, J., Tang, X., Cao, X., & Shen, L. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.813304 · Cited by 201 · see citing works
A Systematic Review of the Valproic-Acid-Induced Rodent Model of Autism
Chaliha, D. R., Albrecht, M. A., Vaccarezza, M., Takechi, R., Lam, V., Al‐Salami, H., & Mamo, J. C. L. (2020) · Developmental Neuroscience · doi:10.1159/000509109 · Cited by 173 · see citing works
Wu, H., Wang, X., Gao, J., Liang, S., Hao, Y., Sun, C., Xia, W., Cao, Y., & Wu, L. (2017) · Life Sciences · doi:10.1016/j.lfs.2017.01.012 · Cited by 138 · see citing works
Tartaglione, A. M., Schiavi, S., Calamandrei, G., & Trezza, V. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.12.024 · Cited by 112 · see citing works
Pharmacological modulation of AMPA receptor rescues social impairments in animal models of autism
Kim, J., Park, K., Kang, R. J., Gonzales, E. L., Kim, D. G., Oh, H. A., Seung, H., Ko, M. J., Kwon, K. J., Kim, K. C., et al. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0098-5 · Cited by 106 · see citing works
Tian, J., Gao, X., & Yang, L. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.780407 · Cited by 125 · see citing works
Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders
Gandhi, T., & Lee, C. C. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.592710 · Cited by 94 · see citing works
Negative geotaxis: An early age behavioral hallmark to VPA rat model of autism
Ruhela, R. K., Soni, S., Sarma, P., Prakash, A., & Medhi, B. (2019) · Annals of Neurosciences · doi:10.5214/ans.0972.7531.260106 · Cited by 81 · see citing works
El-Ansary, A. K., Bacha, A. G. B., Bjørklund, G., Al-Orf, N., Bhat, R. S., Moubayed, N., & Aabed, K. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-018-0212-8 · Cited by 79 · see citing works
Mirza, R., & Sharma, B. (2019) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2019.02.003 · Cited by 78 · see citing works
Wu, H., Luan, Y., Wang, H., Zhang, P., Liu, S., Wang, P., Cao, Y., Sun, H., & Wu, L. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.02.018 · Cited by 77 · see citing works
Al-Askar, M., Bhat, R. S., Selim, M. E., AL-Ayadhi, L. Y., & El-Ansary, A. K. (2017) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-017-1763-7 · Cited by 59 · see citing works
Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors
Barua, S., Kim, J. Y., Kim, J. Y., Kim, J. H., & Lee, J. E. (2019) · Neurochemical Research · doi:10.1007/s11064-018-02712-1 · Cited by 57 · see citing works
Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder
Zárate-López, D., Torres-Chávez, A. L., Gálvez‐Contreras, A. Y., & González-Pérez, Ó. (2023) · Current Neuropharmacology · doi:10.2174/1570159x22666231003121513 · Cited by 56 · see citing works
Mohammadi, S., Asadi‐Shekaari, M., Basiri, M., Parvan, M., Shabani, M., & Nozari, M. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05357-2 · Cited by 57 · see citing works
Zhong, H., Xiao, R., Ruan, R., Liu, H., Li, X., Cai, Y., Zhao, J., & Fan, X. (2020) · Psychopharmacology · doi:10.1007/s00213-020-05634-5 · Cited by 54 · see citing works
Ornoy, A., Weinstein‐Fudim, L., & Ergaz, Z. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051074 · Cited by 52 · see citing works
Wu, H., Zhao, G., Liu, S., Zhang, Q., Wang, P., Cao, Y., & Wu, L. (2022) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109034 · Cited by 52 · see citing works
Kuo, H., & Liu, F. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00422 · Cited by 46 · see citing works
Gąssowska-Dobrowolska, M., Kolasa, A., Cieślik, M., Dominiak, A., Friedland, K., & Adamczyk, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22063209 · Cited by 45 · see citing works
Abhishek, M., Singla, R., Kumar, R., Rupa, J., Sarma, P., Gurjeet, K., Raj, S. A., Prajapat, M., Alka, B., Ramprasad, P., et al. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.115199 · Cited by 44 · see citing works
Bench to bedside review: Possible role of vitamin D in autism spectrum disorder
Jia, F., Shan, L., Wang, B., Li, H., Miao, C., Xu, Z., Lin, C., & Saad, K. (2017) · Psychiatry Research · doi:10.1016/j.psychres.2017.12.005 · Cited by 44 · see citing works
Sato, A., Kotajima‐Murakami, H., Tanaka, M., Katoh, Y., & Ikeda, K. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.821455 · Cited by 42 · see citing works
Long, J., Li, H., Liu, Y., Liao, X., Tang, Z., Han, K., Chen, J., & Zhang, H. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1364858 · Cited by 43 · see citing works
Yang, J., Fu, X. B., Liao, X., & Li, Y. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.561998 · Cited by 40 · see citing works
The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders
Lee, K. C., Mills, Z., Cheung, P. Y., Cheyne, J. E., & Montgomery, J. M. (2022) · Pharmaceuticals · doi:10.3390/ph16010001 · Cited by 40 · see citing works
Anshu, K., Nair, A. K., Kumaresan, U. D., Kutty, B. M., Srinath, S., & Laxmi, T. R. (2017) · Autism Research · doi:10.1002/aur.1852 · Cited by 36 · see citing works
Wu, H., Zhang, Q., Gao, J., Sun, C., Wang, J., Xia, W. T., Cao, Y., Hao, Y., & Wu, L. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4805-4 · Cited by 35 · see citing works
Neuroprotection by agmatine: Possible involvement of the gut microbiome?
Saha, P., Panda, S., Holkar, A., Vashishth, R., Rana, S. S., Arumugam, M., Ashraf, G. M., Haque, S., & Ahmad, F. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102056 · Cited by 35 · see citing works
Neurobiological Mechanisms of Autism Spectrum Disorder and Epilepsy, Insights from Animal Models
Sierra-Arregui, T., Llorente, J., Mı́nguez, P., Tønnesen, J., & Peñagarikano, O. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.02.043 · Cited by 32 · see citing works
A dynamic mouse peptidome landscape reveals probiotic modulation of the gut-brain axis
Zhang, P., Wu, X., Liang, S., Shao, X., Wang, Q., Chen, R., Zhu, W., Shao, C., Jin, F., & Jia, C. (2020) · Science Signaling · doi:10.1126/scisignal.abb0443 · Cited by 32 · see citing works
Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation
Kang, M.-S., Choi, T.-Y., Ryu, H. G., Lee, D., Lee, S., Choi, S., & Kim, K. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20160974 · Cited by 29 · see citing works
Yang, J., Yang, C., & Yin, B.-Q. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.113094 · Cited by 31 · see citing works
Advances in the Treatment of Autism Spectrum Disorder: Current and Promising Strategies
Yenkoyan, K. B., Ounanian, Z., Mirumyan, M., Hayrapetyan, L., Zakaryan, N., Sahakyan, R., & Bjørklund, G. (2023) · Current Medicinal Chemistry · doi:10.2174/0109298673252910230920151332 · Cited by 31 · see citing works
Mehra, S., Ahsan, A. U., Seth, E., & Chopra, M. (2022) · Journal of Molecular Neuroscience · doi:10.1007/s12031-022-02033-7 · Cited by 26 · see citing works
Decreased plasma agmatine levels in autistic subjects
Esnafoğlu, E., & İrende, İ. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-017-1836-2 · Cited by 26 · see citing works
Singla, R., Mishra, A., Joshi, R., Kumar, R., Sarma, P., Sharma, A. R., Kaur, G., Bhatia, A., & Medhi, B. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00672 · Cited by 24 · see citing works
Crespi, B. J. (2019) · Evolution Medicine and Public Health · doi:10.1093/emph/eoz022 · Cited by 23 · see citing works
Gastrodin Rescues Autistic-Like Phenotypes in Valproic Acid-Induced Animal Model
Wang, X., Tao, J., Qiao, Y., Luo, S., Zhao, Z., Gao, Y., Guo, J., Kong, J., Chen, C., Ge, L., et al. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.01052 · Cited by 21 · see citing works
Dobrovolsky, A., Gedzun, V. R., Bogin, V., Ma, D., Ichim, T. E., Sukhanova, I. A., Малышев, А. В., & Дубынин, В. А. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-02161-6 · Cited by 20 · see citing works
Elgamal, M. A., Khodeer, D. M., Abdel‐Wahab, B. A., Ibrahim, I. A. A., Alzahrani, A. R., Moustafa, Y. M., Ali, A. A., & El-Sayed, N. M. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1113966 · Cited by 20 · see citing works
Deemyad, T., Puig, S., Papale, A. E., Qi, H., LaRocca, G. M., Aravind, D., LaNoce, E., & Urban, N. N. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhab233 · Cited by 20 · see citing works
Does caffeine therapy improve cognitive impairments in valproic acid rat model of autism?
Rajizadeh, M. A., Afarinesh, M. R., Zarif, M., Mirasadi, A., & Esmaeilpour, K. (2019) · Toxin Reviews · doi:10.1080/15569543.2019.1680563 · Cited by 19 · see citing works
Hughes, E. M., Calcagno, P., Clarke, M., Sánchez, C., Smith, K. L., Kelly, J. P., Finn, D. P., & Roche, M. (2020) · Brain Research · doi:10.1016/j.brainres.2020.146675 · Cited by 19 · see citing works
Gene-environment interaction counterbalances social impairment in mouse models of autism
Kim, J., Park, K., Kang, R. J., Gonzales, E. L., Oh, H. A., Seung, H., Ko, M. J., Cheong, J. H., Chung, C., & Shin, C. Y. (2019) · Scientific Reports · doi:10.1038/s41598-019-47680-w · Cited by 18 · see citing works
Denucci, B. L., de Lima, L. S., Mota, I. F. L., Azevedo, J. R. M., Veras, L. G., Bicca, J. V. M. L., Santana, B. D. M., Pinheiro, G. B., Coelho, G. G., & Mortari, M. R. (2021) · Reproductive Toxicology · doi:10.1016/j.reprotox.2021.10.010 · Cited by 17 · see citing works
Agmatine relieves behavioral impairments in Fragile X mice model
Jeon, S. J., Kwon, H., Bae, H. J., Gonzales, E. L., Kim, J.-H., Chung, H. J., Kim, D. H., Ryu, J. H., & Shin, C. Y. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109234 · Cited by 17 · see citing works
Di, Y., Li, Z., Li, J., Cheng, Q., Zheng, Q., Zhai, C., Kang, M., Wei, C., Lan, J., Fan, J., et al. (2021) · Food & Function · doi:10.1039/d0fo02926b · Cited by 17 · see citing works
Mishra, A., Singla, R., Kumar, R., Sharma, A. R., Joshi, R., Sarma, P., Kaur, G., Prajapat, M., Bhatia, A., & Medhi, B. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00270 · Cited by 14 · see citing works
Yong, Q., Zhao, C., Xia, L., Zhu, T., & Xia, K. (2025) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s533813 · Cited by 14 · see citing works
Singla, R., Mishra, A., Joshi, R., Sarma, P., Kumar, R., Kaur, G., Sharma, A. R., Jain, A., Prakash, A., Bhatia, A., et al. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.09.003 · Cited by 13 · see citing works
Ornoy, A., Koren, G., & Yanai, J. (2018) · Reproductive Toxicology · doi:10.1016/j.reprotox.2018.05.006 · Cited by 13 · see citing works
D’Antoni, S., Schiavi, S., Buzzelli, V., Giuffrida, S., Feo, A., Ascone, F., Busceti, C. L., Nicoletti, F., Trezza, V., & Catania, M. V. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06457-w · Cited by 12 · see citing works
Animal models of autism: a perspective from autophagy mechanisms
Dana, H., Tahtasakal, R., & Şener, E. F. (2020) · Journal of Translational Genetics and Genomics · doi:10.20517/jtgg.2020.25 · Cited by 12 · see citing works
Altered Grooming Syntax and Amphetamine-Induced Dopamine Release in EAAT3 Overexpressing Mice
Escobar, A. P., Martínez-Pinto, J., Silva-Olivares, F., Sotomayor‐Zárate, R., & Moya, P. R. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.661478 · Cited by 15 · see citing works
Chen, S., Xu, Q., Zhao, L., Zhang, M.-L., & Xu, H. (2024) · Birth Defects Research · doi:10.1002/bdr2.2336 · Cited by 10 · see citing works
Kim, J., Oh, H. A., Kim, S. R., Ko, M. J., Seung, H., Lee, S. H., & Shin, C. Y. (2020) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2020.027 · Cited by 10 · see citing works
Chauhan, R., Mohan, M., Mannan, A., Devi, S., & Singh, T. G. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114654 · Cited by 9 · see citing works
Wu, M., Di, Y., Diao, Z., Yao, L., Qian, Z., Wei, C., Zheng, Q., Liu, Y., Han, J., Liu, Z., et al. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112836 · Cited by 8 · see citing works
Mohamed, A. F., El-Gammal, M. A., El-Yamany, M. F., & Khodir, A. E. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.111192 · Cited by 8 · see citing works
He, J., Lin, Z., Lin, X., Wang, C., Cao, M., Xia, R., & Hong, W. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.106162 · Cited by 7 · see citing works
Ibáñez-Sandoval, D. N., Hidalgo-Balbuena, A. E., Contreras, R. V., Saderi, N., Flores, G., Rueda‐Orozco, P. E., & Ibáñez-Sandoval, O. (2024) · eNeuro · doi:10.1523/eneuro.0326-24.2024 · Cited by 8 · see citing works
Parvan, M., Nozari, M., Shabani, M., Nozari, H., Kohlmeier, K. A., & Mohammadi, S. (2024) · Birth Defects Research · doi:10.1002/bdr2.2379 · Cited by 6 · see citing works
Developmental Trajectory of Autistic‐Like Behaviors in a Prenatal Valproic Acid Rat Model of Autism
Lian, B., He, Y., Dong, D., Quan, L., Feng, T., & Li, M. (2024) · Developmental Psychobiology · doi:10.1002/dev.70008 · Cited by 6 · see citing works
Tadas, M., Wankhede, N. L., Chandurkar, P. A., Kotagale, N. R., Umekar, M. J., Katariya, R., Waghade, A. M., Kokare, D. M., & Taksande, B. G. (2025) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2025.174030 · Cited by 6 · see citing works
Can memantine treat autism? Answers from preclinical and clinical studies
Aboul‐Fotouh, S., Zohny, S. M., Elnahas, E. M., Habib, M. Z., & Hassan, G. A. M. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106019 · Cited by 5 · see citing works
Kim, S., Kim, D. G., Gonzales, E. L., Mabunga, D. F. N., Shin, D., Jeon, S. J., Shin, C. Y., Ahn, T., & Kwon, K. J. (2018) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2018.230 · Cited by 4 · see citing works
Adıgüzel, E., Bağçovan, B., Bozkurt, N. M., Ünal, G., & Waszkiewicz, N. (2026) · Nutrients · doi:10.3390/nu18050777 · Cited by 4 · see citing works
Aboul‐Fotouh, S., Zohny, S. M., Hassan, G. A. M., Eissa, A. M., ElShahawi, H. H., Abdelraouf, S. M., Ahmed, M. Y., Rabei, M. R., Hassan, F. E., Mahmoud, A. N., et al. (2025) · NeuroToxicology · doi:10.1016/j.neuro.2025.103350 · Cited by 4 · see citing works
Khoram-Abadi, K. M., Haratizadeh, S., Basiri, M., Parvan, M., Pourjafari, F., Aghaei, I., Amiresmaili, S., & Nozari, M. (2024) · PubMed Central · doi:10.22038/ijbms.2023.74536.16190 · Cited by 4 · see citing works
Adil, K. J., Remonde, C. G., Gonzales, E. L., Boo, K.-J., Kwon, K. J., Kim, D. H., Kim, H. J., Cheong, J. H., Shin, C. Y., & Jeon, S. J. (2022) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2021.194 · Cited by 4 · see citing works
Kital, K., Traoré, M., Sarr, D., Mbaye, M., Mbaye, O. M. A., Cissé, L., Seye, M. D. G., Coly, A., Delattre, F., & Tine, A. (2019) · Journal of Chemistry and Biochemistry · doi:10.15640/jcb.v7n1a2 · Cited by 4 · see citing works
Adıgüzel, E., Bozkurt, N. M., Ünal, G., & Waszkiewicz, N. (2025) · Biology · doi:10.3390/biology14081065 · Cited by 3 · see citing works
Agmatine ameliorates valproic acid‐induced depletion of parvalbumin‐positive neuron
Khoram-Abadi, K. M., Basiri, M., Nemati, M., & Nozari, M. (2024) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.10314 · Cited by 3 · see citing works
Models of Autism and Methods for Assessing Autistic-Like Behavior in Animals
Асатовна, С. А., Lopatina, O. L., & Salmina, A. B. (2020) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-020-01002-0 · Cited by 3 · see citing works
Reinforced behavioral variability in the valproate rat model of autism spectrum disorder
Galizio, A., & Odum, A. L. (2022) · Journal of the Experimental Analysis of Behavior · doi:10.1002/jeab.760 · Cited by 3 · see citing works
Effect of WiFi signal exposure in utero and early life on neurodevelopment and behaviors of rats
Wu, H., Min, D., Sun, B., Ma, Y., Chen, H., Wu, J., Ren, P., Wu, J., Cao, Y., Zhao, B., et al. (2023) · Environmental Science and Pollution Research · doi:10.1007/s11356-023-29159-4 · Cited by 3 · see citing works
A snapshot on introspection of autism spectrum disorder
Kale, G., Addepalli, V., & Joshi, S. (2024) · Molecular Biology Reports · doi:10.1007/s11033-024-09514-5 · Cited by 3 · see citing works
Kital, K., Traoré, M., Sarr, D., Mbaye, M., Seye, M. D. G., Coly, A., Delattre, F., & Tine, A. (2020) · Journal of Analytical Science & Technology · doi:10.1186/s40543-020-00238-2 · Cited by 3 · see citing works
Pérez‐Sisqués, L., Bhatt, S., Caruso, A., Ahmed, M. U., Gileadi, T. E., Spring, S., Hendy, E., Taylor‐Papadimitriou, J., Cash, D., Clifton, N. E., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.28.596232 · Cited by 3 · see citing works
Low-frequency RTMS attenuates social impairment in the VPA-induced mouse model
Wang, X., Li, Y., Rui, L. I., Yuan, L., Hua, Y., Cai, Y., & Liu, X. (2024) · Behavioural Brain Research · doi:10.1016/j.bbr.2024.115156 · Cited by 2 · see citing works
Pretorius, L., Coetzee, J. A., dos Santos, A. P., & Smith, C. (2025) · Molecular Medicine · doi:10.1186/s10020-025-01232-3 · Cited by 2 · see citing works
Aghoghovwia, B. E., Okpe, O., McIntyre, E., Taniyohwo, E. M., & Ratnayake, J. T. (2021) · Current Stem Cell Reports · doi:10.1007/s40778-021-00189-3 · Cited by 1 · see citing works
Neelotpol, S., Rezwan, R., Singh, T., Mayesha, I. I., Saba, S., & Jamiruddin, M. R. (2024) · PLoS ONE · doi:10.1371/journal.pone.0308632 · Cited by 1 · see citing works
Tanizaki, M., Matsui, T., Sugiyama, R., Kiriyama, N., & Komada, M. (2025) · Toxicology Letters · doi:10.1016/j.toxlet.2025.09.004 · Cited by 1 · see citing works
Pérez‐Sisqués, L., Bhatt, S. R., Caruso, A., Robb, J. L., Donovan, A. P. A., Bamford, R. A., Torres-Cano, A., Spring, S., Hendy, E., Gileadi, T. E., et al. (2026) · Science Advances · doi:10.1126/sciadv.adq6577 · Cited by 1 · see citing works
Rode, M. R., Kolhe, S. U., & Patil, C. N. (2024) · Brain Disorders · doi:10.1016/j.dscb.2024.100128 · Cited by 1 · see citing works
El-Ansary, A. K., Al-Dbass, A. M., & Qasem, H. (2018) · InTech eBooks · doi:10.5772/intechopen.69431 · Cited by 2 · see citing works
Shih, Y.-C., Nelson, L., Janeček, M., & Peixoto, R. T. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.23.568500 · Cited by 1 · see citing works
Energy metabolism and autism: the ameliorative potential of carnosine and agmatine
Hipkiss, A. R. (2018) · Neurological Disorders and Therapeutics · doi:10.15761/ndt.1000135
Xu, Q., Li, X., Lin, J., Zhang, M.-L., He, T., Huang, W., & Hui-qin, X. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3979570
Cezar, L. C. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.10.2022.tde-20012023-112002
Tahiroğlu, V., Çağlayan, C., Güleç, A. G., Öztürk, S. Y., Karageçili, H., & Çağlar, T. (2025) · Turkish Journal of Biochemistry · doi:10.1515/tjb-2024-0394
Bilim, P., Çelik, K., Garip, G., Yardımcı, A. G., Yardımcı, B. Ş., & Baka, M. (2025) · Ege Tıp Dergisi · doi:10.19161/etd.1686034
Eid, L. T. M., El-Habeby, M. M., Issa, N. M., & Nooreldien, N. M. (2025) · Tissue and Cell · doi:10.1016/j.tice.2025.103062
Behavioral Effects of Agmatine in a Valproic Acid-Induced Rat Model of Autism Spectrum Disorder
Arıcıoğlu, F., Kabacaoğlu, G., Korkmaz, E., Bahtiyar, B. C., Sümer, E., & Yılmaz, B. (2025) · Clinical and Experimental Health Sciences · doi:10.33808/clinexphealthsci.1812820
- Authors
- Kim, J.-W., Seung, H., Kim, K. C., Gonzales, E. L. T., Oh, H. A., Yang, S. M., Ko, M. J., Han, S.-H., Banerjee, S., & Shin, C. Y.
- Affiliations
- Konkuk University (KR)
- National Brain Research Centre (IN)
- Corresponding author
- Shin, Chan Young
- ORCID
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 113
- Issue
- Pt A
- Pages
- 71-81
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2519436935
- Cited by
- 102
- References
- 65
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 13 · 2023: 8 · 2022: 14 · 2021: 10 · 2020: 11 · 2019: 11 · 2018: 13 · 2017: 6
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea
- Korea government (2014R1A2A2A01003079, 2016R1A5A2012284)
- Korea Health industry Development Institute
- Ministry of Health & Welfare, Republic of Korea (HI12C0021)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- agmatine, autism spectrum disorder, excitatory-inhibitory imbalance, NMDA receptor antagonists, social behavior deficits, repetitive behavior, hyperactivity, ERK signaling, prefrontal cortex, hippocampus, glutamatergic neurons, GABAergic neurons, autism treatment
- MeSH terms
- Autism Spectrum Disorder, Agmatine, Animals, Disease Models, Animal, Grooming, Hippocampus, Hyperkinesis, Male, Mice, Transgenic, Neurons, Seizures, Social Behavior, Valproic Acid, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Prefrontal Cortex, MAP Kinase Signaling System, Mice, Rats, Neural Stem Cells, Primary Cell Culture
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
