Abstract
This paper reviews the utility of zebrafish (Danio rerio) as a model system for exploring neurobehavioral phenomena in preclinical research, focusing on physiological processes, disorders, and neurotoxicity biomarkers. A comprehensive review of the current literature was conducted to summarize the various behavioral characteristics of zebrafish. The study examined the etiological agents used to induce neurotoxicity and the biomarkers involved, including Aβ42, tau, MMP-13, MAO, NF-Кβ, and GFAP. Additionally, the different zebrafish study models and their responses to neurobehavioral analysis were discussed. The review identified several key biomarkers of neurotoxicity in zebrafish, each impacting different aspects of neurogenesis, inflammation, and neurodegeneration. Aβ42 was found to alter neuronal growth and stem cell function. Tau’s interaction with tubulin affected microtubule stability and led to tauopathies under pathological conditions. MMP-13 was linked to oxidative assault and sensory neuron degeneration. MAO plays a role in neurotransmitter metabolism and neurotoxicity conversion. NF-Кβ was involved in pro-inflammatory pathways, and GFAP was indicative of neuroinflammation and astroglial activation. Zebrafish provide a valuable model for neurobehavioral research, adhering to the “3Rs” philosophy. Their neurotoxicity biomarkers offer insights into the mechanisms of neurogenesis, inflammation, and neurodegeneration. This model system aids in evaluating physiological and pathological conditions, enhancing our understanding of neurobehavioral phenomena and potential therapeutic interventions.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
No datasets were generated or analyzed during the current study.
References
Agbo J, Ibrahim ZG, Magaji SY, Mutalub YB, Mshelia PP, Mhyha DH (2023) Therapeutic efficacy of voltage-gated sodium channel inhibitors in epilepsy. Acta Epileptologica 5(1):16. https://doi.org/10.1186/s42494-023-00127-2
Aldurrah Z, Kauli FS, Rahim NA, Zainal Z, Afzan A, Al Zarzour RH, Salhimi SM, Zain MS, Zakaria F (2023) Antidepressant evaluation of Andrographis paniculata Nees extract and andrographolide in chronic unpredictable stress zebrafish model. Comp Biochem Physiol c: Toxicol Pharmacol 271:109678. https://doi.org/10.1016/j.cbpc.2023.109678
Annunziato M, Eeza MN, Bashirova N, Lawson A, Matysik J, Benetti D, Grosell M, Stieglitz JD, Alia A, Berry JP (2022) An integrated systems-level model of the toxicity of brevetoxin based on high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR) metabolic profiling of zebrafish embryos. Sci Total Environ 803:149858. https://doi.org/10.1016/j.scitotenv.2021.149858
Arvigo AL, Miyai CA, Sanches FH, Barreto RE, Costa TM (2019) Combined effects of predator odor and alarm substance on behavioral and physiological responses of the pearl cichlid. Physiol Behav 206:259–263. https://doi.org/10.1016/j.physbeh.2019.02.032
Bai C, Tang M (2020) Toxicological study of metal and metal oxide nanoparticles in zebrafish. J Appl Toxicol 40(1):37–63. https://doi.org/10.1002/jat.3910
Bandara SB, Carty DR, Singh V, Harvey DJ, Vasylieva N, Pressly B, Wulff H, Lein PJ (2020) Susceptibility of larval zebrafish to the seizurogenic activity of GABA type A receptor antagonists. Neurotoxicology 76:220–234. https://doi.org/10.1016/j.neuro.2019.12.001
Barrios JP, Wang WC, England R, Reifenberg E, Douglass AD (2020) Hypothalamic dopamine neurons control sensorimotor behavior by modulating brainstem premotor nuclei in zebrafish. Curr Biol 30(23):4606–4618. https://doi.org/10.1016/j.cub.2020.09.002
Bashirzade AA, Zabegalov KN, Volgin AD, Belova AS, Demin KA, de Abreu MS, Babchenko VY, Bashirzade KA, Yenkoyan KB, Tikhonova MA, Amstislavskaya TG (2022) Modeling neurodegenerative disorders in zebrafish. Neurosci Biobehav Rev 138:104679. https://doi.org/10.1016/j.neubiorev.2022.104679
Basnet RM, Zizioli D, Taweedet S, Finazzi D, Memo M (2019) Zebrafish larvae as a behavioral model in neuropharmacology. Biomedicines 7(1):23. https://doi.org/10.3390/biomedicines7010023
Beppi C, Straumann D, Bögli SY (2021) A model-based quantification of startle reflex habituation in larval zebrafish. Sci Rep 11(1):846. https://doi.org/10.1038/s41598-020-79923-6
Biju A, Ivantsova E, Souders CL II, English C, Avidan L, Martyniuk CJ (2024) Exposure to the pharmaceutical buspirone alters locomotor activity, anxiety-related behaviors, and transcripts related to serotonin signaling in larval zebrafish (Danio rerio). Neurotoxicol Teratol 101:107318. https://doi.org/10.1016/j.ntt.2023.107318
Brodie MJ, Besag F, Ettinger AB, Mula M, Gobbi G, Comai S, Aldenkamp AP, Steinhoff BJ (2016) Epilepsy, antiepileptic drugs, and aggression: an evidence-based review. Pharmacol Rev 68(3):563–602. https://doi.org/10.1124/pr.115.012021
Brun NR, Van Hage P, Hunting ER, Haramis AP, Vink SC, Vijver MG, Schaaf MJ, Tudorache C (2019) Polystyrene nanoplastics disrupt glucose metabolism and cortisol levels with a possible link to behavioural changes in larval zebrafish. Communications Biology 2(1):382. https://doi.org/10.1038/s42003-019-0629-6
Buatois A, Gerlai R (2020) Elemental and configural associative learning in spatial tasks: could zebrafish be used to advance our knowledge? Front Behav Neurosci 14:570704. https://doi.org/10.3389/fnbeh.2020.570704
Capriello T, Di Meglio G, De Maio A, Scudiero R, Bianchi AR, Trifuoggi M, Toscanesi M, Giarra A, Ferrandino I (2022) Aluminium exposure leads to neurodegeneration and alters the expression of marker genes involved to parkinsonism in zebrafish brain. Chemosphere 307:135752. https://doi.org/10.1016/j.chemosphere.2022.135752
Cario A, Berger CL (2023) Tau, microtubule dynamics, and axonal transport: new paradigms for neurodegenerative disease. BioEssays 45(8):2200138. https://doi.org/10.1002/bies.202200138
Chen X, Huang C, Wang X, Chen J, Bai C, Chen Y, Chen X, Dong Q, Yang D (2012) BDE-47 disrupts axonal growth and motor behavior in develo** zebrafish. Aquat Toxicol 120:35–44. https://doi.org/10.1016/j.aquatox.2012.04.014
Cirrincione AM, Pellegrini AD, Dominy JR, Benjamin ME, Utkina-Sosunova I, Lotti F, Jergova S, Sagen J, Rieger S (2020) Paclitaxel-induced peripheral neuropathy is caused by epidermal ROS and mitochondrial damage through conserved MMP-13 activation. Sci Rep 10(1):3970. https://doi.org/10.1038/s41598-020-60990-8
Costa FV, Zabegalov KN, Kolesnikova TO, de Abreu MS, Kotova MM, Petersen EV, Kalueff AV (2023) Experimental models of human cortical malformations: from mammals to zebrafish. Neurosci Biobehav Rev 18:105429. https://doi.org/10.1016/j.neubiorev.2023.105429
Crouzier L, Richard EM, Sourbron J, Lagae L, Maurice T, Delprat B (2021) Use of zebrafish models to boost research in rare genetic diseases. Int J Mol Sci 22(24):13356. https://doi.org/10.3390/ijms222413356
Cui L, Hou NN, Wu HM, Zuo X, Lian YZ, Zhang CN, Wang ZF, Zhang X, Zhu JH (2022) Prevalence of Alzheimer’s disease and Parkinson’s disease in China: an updated systematical analysis. Front Aging Neurosci 21(12):603854. https://doi.org/10.3389/fnagi.2020.603854
Czarny-Krzymińska K, Krawczyk B, Szczukocki D (2023) Bisphenol A and its substitutes in the aquatic environment: occurrence and toxicity assessment. Chemosphere 315:137763. https://doi.org/10.1016/j.chemosphere.2023.137763
Dew WA, Wood CM, Pyle GG (2012) Effects of continuous copper exposure and calcium on the olfactory response of fathead minnows. Environ Sci Technol 46(16):9019–9026. https://doi.org/10.1021/es300670p
Dos Santos CP, de Oliveira MN, Silva PF, Luchiari AC (2023) Relationship between boldness and exploratory behavior in adult zebrafish. Behav Proc 209:104885. https://doi.org/10.1016/j.beproc.2023.104885
Doyle JM, Croll RP (2022) A critical review of zebrafish models of Parkinson’s disease. Front Pharmacol 13:835827. https://doi.org/10.3389/fphar.2022.835827
Echevarria DJ, Caramillo EM, Gonzalez-Lima F (2016) Methylene blue facilitates memory retention in zebrafish in a dose-dependent manner. Zebrafish 13(6):489–494. https://doi.org/10.1089/zeb.2016.1282
Ek F, Malo M, Åberg Andersson M, Wedding C, Kronborg J, Svensson P, Waters S, Petersson P, Olsson R (2016) Behavioral analysis of dopaminergic activation in zebrafish and rats reveals similar phenotypes. ACS Chem Neurosci 7(5):633–646. https://doi.org/10.1021/acschemneuro.6b00014
Ende G, Cackowski S, Van Eijk J, Sack M, Demirakca T, Kleindienst N, Bohus M, Sobanski E, Krause-Utz A, Schmahl C (2016) Impulsivity and aggression in female BPD and ADHD patients: association with ACC glutamate and GABA concentrations. Neuropsychopharmacology 41(2):410–418. https://doi.org/10.1038/npp.2015.153
Espay AJ, Lees AJ (2024) Loss of monomeric alpha-synuclein (synucleinopenia) and the origin of Parkinson’s disease. Parkinsonism Relat Disord 3:106077. https://doi.org/10.1016/j.parkreldis.2024.106077
Fagundes BH, Nascimento PC, Aragão WA, Chemelo VS, Bittencourt LO, Eiró-Quirino L, Silva MC, Freire MA, Fernandes LM, Maia CD, Crespo-Lopez ME (2022) Methylmercury exposure during prenatal and postnatal neurodevelopment promotes oxidative stress associated with motor and cognitive damages in rats: an environmental-experimental toxicology study. Toxicol Rep 9:563–574. https://doi.org/10.1016/j.toxrep.2022.02.014
Fanning JR, Lee R, Coccaro EF (2020) Neurotransmitter function in impulsive aggression and intermittent explosive disorder. Wiley Int Handbook Psych Disord Law 17:249–269. https://doi.org/10.1002/9781119159322.ch10
Faria M, Prats E, Bellot M, Gomez-Canela C, Raldúa D (2021) Pharmacological modulation of serotonin levels in zebrafish larvae: lessons for identifying environmental neurotoxicants targeting the serotonergic system. Toxics 9(6):118. https://doi.org/10.3390/toxics9060118
Fortier G, Butti Z, Patten SA (2020) Modelling C9orf72-related amyotrophic lateral sclerosis in zebrafish. Biomedicines 8(10):440. https://doi.org/10.3390/biomedicines8100440
Franco-Restrepo JE, Vargas RA (2021) Behavioural and molecular effects of alcohol in the stress model of zebrafish. Indian J Physiol Pharmacol 65(3):153–61. https://doi.org/10.25259/ijpp_57_2021
Gerlai R (2016) Learning and memory in zebrafish (Danio rerio). InMethods Cell Biol 134:551–586. https://doi.org/10.1016/bs.mcb.2016.02.005
Gerlai RT (2020) Fear responses and antipredatory behavior of zebrafish: a translational perspective. InBehav Neur Genet Zebrafish 155–171. https://doi.org/10.1016/b978-0-12-817528-6.00010-3
Grossman L, Utterback E, Stewart A, Gaikwad S, Chung KM, Suciu C, Wong K, Elegante M, Elkhayat S, Tan J, Gilder T (2010) Characterization of behavioral and endocrine effects of LSD on zebrafish. Behav Brain Res 214(2):277–284. https://doi.org/10.1016/j.bbr.2010.05.039
Gu J, Li L, Yin X, Liang M, Zhu Y, Guo M, Zhou L, Fan D, Shi L, Ji G (2022) Long-term exposure of zebrafish to bisphenol F: adverse effects on parental reproduction and offspring neurodevelopment. Aquat Toxicol 248:106190. https://doi.org/10.1016/j.aquatox.2022.106190
Gupta R, Tekade M, Vasdev N, Gupta T, Pawar B, Bansal KK, Tekade RK (2023) Mechanism of drug-induced neurotoxicity and its management. Essentials Pharmatoxicol Drug Res 1:317–341. https://doi.org/10.1016/B978-0-443-15840-7.00006-3
Harvey PD (2019) Domains of cognition and their assessment. Dialogues Clin Neurosci 21(3):227–37. https://doi.org/10.31887/dcns.2019.21.3/pharvey
Herpertz SC, Nagy K, Ueltzhöffer K, Schmitt R, Mancke F, Schmahl C, Bertsch K (2017) Brain mechanisms underlying reactive aggression in borderline personality disorder—sex matters. Biol Psychiat 82(4):257–266. https://doi.org/10.1016/j.biopsych.2017.02.1175
Jain S, Jain A, Jain R, Thakur SS, Jain SK (2022) Wnt, BMP and Sox mediated gene dysregulationvia endocrine disrupting chemicals BPA and BPS; studies in neurogenesis and alteration in brain activity: a review. Bull Pure Appl Sci-Zool 41(1):158–168. https://doi.org/10.5958/2320-3188.2022.00019.5
Javed I, Peng G, **ng Y, Yu T, Zhao M, Kakinen A, Faridi A, Parish CL, Ding F, Davis TP, Ke PC (2019) Inhibition of amyloid beta toxicity in zebrafish with a chaperone-gold nanoparticle dual strategy. Nat Commun 10(1):3780. https://doi.org/10.1038/s41467-019-11762-0
Klein MO, Battagello DS, Cardoso AR, Hauser DN, Bittencourt JC, Correa RG (2019) Dopamine: functions, signaling, and association with neurological diseases. Cell Mol Neurobiol 39(1):31–59. https://doi.org/10.1007/s10571-018-0632-3
Komoike Y, Matsuoka M (2022) Developmental adverse effects of trace amounts of lead: evaluation using zebrafish model. Front Pharmacol 13:1014912. https://doi.org/10.3389/fphar.2022.1014912
Koning HK, Ahemaiti A, Boije H (2022) A deep-dive into fictive locomotion–a strategy to probe cellular activity during speed transitions in fictively swimming zebrafish larvae. Biol Open 11(3):bio059167. https://doi.org/10.1242/bio.059167
Kumari S, Dhiman P, Kumar R, Rahmatkar SN, Singh D (2023) Chemo-kindling in adult zebrafish alters spatial cognition but not social novelty recognition. Behav Brain Res 438:114158. https://doi.org/10.1016/j.bbr.2022.114158
Kundap UP, Paudel YN, Kumari Y, Othman I, Shaikh MF (2019) Embelin prevents seizure and associated cognitive impairments in a pentylenetetrazole-induced kindling zebrafish model. Front Pharmacol 10:315. https://doi.org/10.3389/fphar.2019.00315
Lachowicz J, Niedziałek K, Rostkowska E, Szopa A, Świąder K, Szponar J, Serefko A (2021) Zebrafish as an animal model for testing agents with antidepressant potential. Life 11(8):792. https://doi.org/10.3390/life11080792
Langova V, Vales K, Horka P, Horacek J (2020) The role of zebrafish and laboratory rodents in schizophrenia research. Front Psych 11:703. https://doi.org/10.3389/fpsyt.2020.00703
Lee Y, Lee S, Park JW, Hwang JS, Kim SM, Lyoo IK, Lee CJ, Han IO (2018) Hypoxia-induced neuroinflammation and learning–memory impairments in adult zebrafish are suppressed by glucosamine. Mol Neurobiol 55:8738–8753. https://doi.org/10.1007/s12035-018-1017-9
Levitas-Djerbi T, Appelbaum L (2017) Modeling sleep and neuropsychiatric disorders in zebrafish. Curr Opin Neurobiol 44:89–93. https://doi.org/10.1016/j.conb.2017.02.017
Li R, Guo W, Lei L, Zhang L, Liu Y, Han J, Chen L, Zhou B (2020) Early-life exposure to the organophosphorus flame-retardant tris (1, 3-dichloro-2-propyl) phosphate induces delayed neurotoxicity associated with DNA methylation in adult zebrafish. Environ Int 134:105293. https://doi.org/10.1016/j.envint.2019.105293
Li F, Lin J, Liu X, Li W, Ding Y, Zhang Y, Zhou S, Guo N, Li Q (2018) Characterization of the locomotor activities of zebrafish larvae under the influence of various neuroactive drugs. Ann Transl Med 6(10). https://doi.org/10.21037/atm.2018.04.25
Lillesaar C, Gaspar P (2020) Serotonergic neurons in vertebrate and invertebrate model organisms (rodents, zebrafish, Drosophila melanogaster, Aplysia californica, Caenorhabditis elegans). Serotonin 49–80. https://doi.org/10.1016/b978-0-12-800050-2.00003-6
Lopes AC, Peixe TS, Mesas AE, Paoliello MM (2016) Lead exposure and oxidative assault: a systematic review. Rev Environ Contam Toxicol 236(2016):193–238. https://doi.org/10.1007/978-3-319-20013-2_3
Lopez A, Lee SE, Wojta K, Ramos EM, Klein E, Chen J, Boxer AL, Gorno-Tempini ML, Geschwind DH, Schlotawa L, Ogryzko NV (2017) A152T tau allele causes neurodegeneration that can be ameliorated in a zebrafish model by autophagy induction. Brain 140(4):1128–1146. https://doi.org/10.1093/brain/awx005
MacRae CA, Peterson RT (2015) Zebrafish as tools for drug discovery. Nat Rev Drug Discov 14(10):721–31. https://doi.org/10.1038/nrd4627
Marucci G, Buccioni M, Dal Ben D, Lambertucci C, Volpini R, Amenta F (2022) Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. Neuropharmacology 190:108352. https://doi.org/10.1016/j.neuropharm.2020.108352
Maximino C, Marques de Brito T, Dias CA, Gouveia A Jr, Morato S (2010) Scototaxis as anxiety-like behavior in fish. Nat Protoc 5(2):209–216. https://doi.org/10.1038/nprot.2009.225
Meyer DN, Crofts EJ, Akemann C, Gurdziel K, Farr R, Baker BB, Weber D, Baker TR (2020) Developmental exposure to Pb2+ induces transgenerational changes to zebrafish brain transcriptome. Chemosphere 244:125527. https://doi.org/10.1016/j.chemosphere.2019.125527
Moore KB, Hung TJ, Fortin JS (2023) Hyperphosphorylated tau (p-tau) and drug discovery in the context of Alzheimer’s disease and related tauopathies. Drug Discov Today 28(3):103487. https://doi.org/10.1016/j.drudis.2023.103487
Moretz JA, Martins EP, Robison BD (2007) The effects of early and adult social environment on zebrafish (Danio rerio) behavior. Environ Biol Fishes 80:91–101. https://doi.org/10.1007/s10641-006-9122-4
Moussavi Nik SH, Newman M, Ganesan S, Chen M, Martins R, Verdile G, Lardelli M (2014) Hypoxia alters expression of zebrafish microtubule-associated protein Tau (mapta, maptb) gene transcripts. BMC Res Notes 7:1–9. https://doi.org/10.1186/1756-0500-7-767
Nachammai V, Jeyabalan S, Muthusamy S (2021) Anxiolytic effects of silibinin and naringenin on zebrafish model: a preclinical study. Indian J Pharmacol 53(6):457–464. https://doi.org/10.4103/ijp.ijp_18_20
Nadig AP, Suman Sahyadri M, Mehdi S, Krishna KL (2023) Aqueous extract of Piper betle L. leaf and Areca catechu L. nut protects against pentylenetetrazole-induced seizures and positively modulates cognitive function in adult zebrafish. Adv Tradit Med 23(4):1137–52. https://doi.org/10.1007/s13596-022-00664-0
Negi G, Kumar A, Sharma SS (2011) Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes. Curr Neurovasc Res 8(4):294–304. https://doi.org/10.2174/156720211798120972
Norton WH, Manceau L, Reichmann F (2019) The visually mediated social preference test: a novel technique to measure social behavior and behavioral disturbances in zebrafish. Psychiatr Disord: Methods Protoc 121–32. https://doi.org/10.1007/978-1-4939-9554-7_8
Ogi A, Licitra R, Naef V, Marchese M, Fronte B, Gazzano A, Santorelli FM (2021) Social preference tests in zebrafish: a systematic review. Front Vet Sci 7:590057. https://doi.org/10.3389/fvets.2020.590057
Pal S, Mandal S, Firdous SM (2023) Neurobehavioral assessment of seed extract of Swietenia mahagoni on zebrafish model. Bangladesh J Pharmacol 18(4):130–7. https://doi.org/10.3329/bjp.v18i4.67354
Paramakrishnan N, Lim KG, Paramaswaran Y, Ali N, Waseem M, Shazly GA, Bin Jardan YA, Muthuraman A (2023) Astaxanthin: a marine drug that ameliorates cerebrovascular-damage-associated alzheimer’s disease in a zebrafish model via the inhibition of matrix metalloprotease-13. Mar Drugs 21(8):433. https://doi.org/10.3390/md21080433
Park JS, Samanta P, Lee S, Lee J, Cho JW, Chun HS, Yoon S, Kim WK (2021) Developmental and neurotoxicity of acrylamide to zebrafish. Int J Mol Sci 22(7):3518. https://doi.org/10.3390/ijms22073518
Peng X, Lin J, Zhu Y, Liu X, Zhang Y, Ji Y, Yang X, Zhang Y, Guo N, Li Q (2016) Anxiety-related behavioral responses of pentylenetetrazole-treated zebrafish larvae to light-dark transitions. Pharmacol Biochem Behav 145:55–65. https://doi.org/10.1016/j.pbb.2016.03.010
Perdikaris P, Dermon CR (2022) Behavioral and neurochemical profile of MK-801 adult zebrafish model: forebrain β2-adrenoceptors contribute to social withdrawal and anxiety-like behavior. Prog Neuropsychopharmacol Biol Psychiatry 115:110494. https://doi.org/10.1016/j.pnpbp.2021.110494
Pereira P, Korbas M, Pereira V, Cappello T, Maisano M, Canário J, Almeida A (1863) Pacheco M (2019) A multidimensional concept for mercury neuronal and sensory toxicity in fish-From toxicokinetics and biochemistry to morphometry and behavior. Biochim Biophys Acta (BBA)-Gen Subj 12:129298. https://doi.org/10.1016/j.bbagen.2019.01.020
Peres TV, Schettinger MR, Chen P, Carvalho F, Avila DS, Bowman AB, Aschner M (2016) Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies. BMC Pharmacol Toxicol 17:1–20. https://doi.org/10.1186/s40360-016-0099-0
Pisera-Fuster A, Rocco L, Faillace MP, Bernabeu R (2019) Sensitization-dependent nicotine place preference in the adult zebrafish. Prog Neuropsychopharmacol Biol Psychiatry 92:457–469. https://doi.org/10.1016/j.pnpbp.2019.02.018
Pradhan LK, Sarangi P, Sahoo PK, Kundu S, Chauhan NR, Das SK (2023) Bisphenol A-induced neurobehavioral transformation is associated with augmented monoamine oxidase activity and neurodegeneration in zebrafish brain. Environ Toxicol Pharmacol 97:104027. https://doi.org/10.1016/j.etap.2022.104027
Rajput N, Parikh K, Kenney JW (2022) Beyond bold versus shy: zebrafish exploratory behavior falls into several behavioral clusters and is influenced by strain and sex. Biol Open 11(8):bio059443. https://doi.org/10.1242/bio.059443
Ramesh M, Angitha S, Haritha S, Poopal RK, Ren Z, Umamaheswari S (2020) Organophosphorus flame retardant induced hepatotoxicity and brain AChE inhibition on zebrafish (Danio rerio). Neurotoxicol Teratol 82:106919. https://doi.org/10.1016/j.cub.2019.02.039
Rappeneau V, Castillo-Díaz F (2024) Convergence of oxytocin and dopamine signaling in neuronal circuits: insights into the neurobiology of social interactions across species. Neurosci Biobehav Rev 11:105675. https://doi.org/10.1016/j.neubiorev.2024.105675
Ravindranath V, Sundarakumar JS (2021) Changing demography and the challenge of dementia in India. Nat Rev Neurol 17(12):747–758. https://doi.org/10.1038/s41582-021-00565-x
Razali K, Othman N, Mohd Nasir MH, Doolaanea AA, Kumar J, Ibrahim WN, Mohamed Ibrahim N, Mohamed WM (2021) The promise of the zebrafish model for Parkinson’s disease: today’s science and tomorrow’s treatment. Front Genet 12:655550. https://doi.org/10.3389/fgene.2021.655550
Reichmann F, Pilic J, Trajanoski S, Norton WH (2022) Transcriptomic underpinnings of high and low mirror aggression zebrafish behaviours. BMC Biol 20(1):97. https://doi.org/10.1186/s12915-022-01298-z
Rock S, Rodenburg F, Schaaf MJ, Tudorache C (2022) Detailed analysis of zebrafish larval behaviour in the light dark challenge assay shows that diel hatching time determines individual variation. Front physiol 13:827282. https://doi.org/10.3389/fphys.2022.827282
Rodrigues DT, Padilha HA, Soares AT, de Souza ME, Guerra MT, Ávila DS (2024) The Caenorhabditis elegans neuroendocrine system and their modulators: an overview. Mol Cell Endocrinol 112191. https://doi.org/10.1016/j.mce.2024.112191
Romero NG, Gutierrez G, Teixidó E, Li L, Klose J, Leung PC, Cañigueral S, Fritsche E, Barenys M (2023) Developmental neurotoxicity evaluation of three Chinese herbal medicines in zebrafish larvae by means of two behavioral assays: touch-evoked response and light/dark transition. Reprod Toxicol 121:108469. https://doi.org/10.1016/j.reprotox.2023.108469
Rosa JG, Lima C, Lopes-Ferreira M (2022) Zebrafish larvae behavior models as a tool for drug screenings and pre-clinical trials: a review. Int J Mol Sci 23(12):6647. https://doi.org/10.3390/ijms23126647
Sakai C, Ijaz S, Hoffman EJ (2018) Zebrafish models of neurodevelopmental disorders: past, present, and future. Front Mol Neurosci 11:294. https://doi.org/10.3389/fnmol.2018.00294
Salahinejad A, Attaran A, Naderi M, Meuthen D, Niyogi S, Chivers DP (2021) Chronic exposure to bisphenol S induces oxidative stress, abnormal anxiety, and fear responses in adult zebrafish (Danio rerio). Sci Total Environ 750:141633. https://doi.org/10.1016/j.scitotenv.2020.141633
Saleem S, Kannan RR (2022) Zebrafish: a potential preclinical model for neurological research in modern biology. InZebrafish Model Biomed Res 2022:321–345. https://doi.org/10.1007/978-981-16-5217-2_14
Santos D, Luzio A, Matos C, Bellas J, Monteiro SM, Félix L (2021) Microplastics alone or co-exposed with copper induce neurotoxicity and behavioral alterations on zebrafish larvae after a subchronic exposure. Aquat Toxicol 235:105814. https://doi.org/10.1016/j.aquatox.2021.105814
Sarangi P, Pradhan LK, Sahoo PK, Chauhan NR, Das SK (2023) Di-2-ethylhexyl phthalate-induced neurobehavioural transformation is associated with altered glutathione biosynthesis and neurodegeneration in zebrafish brain. Fish Physiol Biochem 49(3):501–514. https://doi.org/10.1007/s10695-023-01197-2
Sathianathan R, Kantipudi SJ (2018) The dementia epidemic: impact, prevention, and challenges for India. Indian J Psychiatry 60(2):165–167. https://doi.org/10.4103/psychiatry.IndianJPsychiatry_261_18
Saverino C, Gerlai R (2008) The social zebrafish: behavioral responses to conspecific, heterospecific, and computer animated fish. Behav Brain Res 191(1):77–87. https://doi.org/10.1016/j.bbr.2008.03.013
Shi Z, Liang X, Zhao Y, Liu W, Martyniuk CJ (2022) Neurotoxic effects of synthetic phenolic antioxidants on dopaminergic, serotoninergic, and GABAergic signaling in larval zebrafish (Danio rerio). Sci Total Environ 830:154688. https://doi.org/10.1016/j.scitotenv.2022.154688
Singh S, Sahu K, Kapil L, Singh C, Singh A (2022) Quercetin ameliorates lipopolysaccharide-induced neuroinflammation and oxidative stress in adult zebrafish. Mol Biol Rep 49(4):3247–3258. https://doi.org/10.1007/s11033-022-07161-2
Sofidiya MO, Alokun AM, Fageyinbo MS, Akindele AJ (2022) Central nervous system depressant activity of ethanol extract of Motandra guineensis (Thonn) AD. aerial parts in mice. Phytomed Plus 2(1):100186. https://doi.org/10.1016/j.phyplu.2021.100186
Song Y, Liu S, Jiang X, Ren Q, Deng H, Paudel YN, Wang B, Liu K, ** M (2022) Benzoresorcinol induces developmental neurotoxicity and injures exploratory, learning and memorizing abilities in zebrafish. Sci Total Environ 834:155268. https://doi.org/10.1016/j.scitotenv.2022.155268
Swain HA, Sigstad C, Scalzo FM (2004) Effects of dizocilpine (MK-801) on circling behavior, swimming activity, and place preference in zebrafish (Danio rerio). Neurotoxicol Teratol 6:725–729. https://doi.org/10.1016/j.ntt.2004.06.009
Tan JK, Nazar FH, Makpol S, Teoh SL (2022a) Zebrafish: a pharmacological model for learning and memory research. Molecules 27(21):7374. https://doi.org/10.3390/molecules27217374
Tan JX, Ang RJ, Wee CL (2022b) Larval zebrafish as a model for mechanistic discovery in mental health. Front Mol Neurosci 15:900213. https://doi.org/10.3389/fnmol.2022.900213
Tao Y, Li Z, Yang Y, Jiao Y, Qu J, Wang Y, Zhang Y (2022) Effects of common environmental endocrine-disrupting chemicals on zebrafish behavior. Water Res 208:117826. https://doi.org/10.1016/j.watres.2021.117826
Thakur M, Rachamalla M, Niyogi S, Datusalia AK, Flora SJ (2021) Molecular mechanism of arsenic-induced neurotoxicity including neuronal dysfunctions. Int J Mol Sci 22(18):10077. https://doi.org/10.3390/ijms221810077
Thawkar BS, Kaur G (2019) Inhibitors of NF-κB and P2X7/NLRP3/caspase 1 pathway in microglia: novel therapeutic opportunities in neuroinflammation induced early-stage Alzheimer’s disease. J Neuroimmunol 326:62–74. https://doi.org/10.1016/j.jneuroim.2018.11.010
Thawkar BS, Kaur G (2021) Zebrafish as a promising tool for modeling neurotoxin-induced Alzheimer’s disease. Neurotox Res 39:949–965. https://doi.org/10.1007/s12640-021-00343-z
Toms CN, Echevarria DJ (2014) Back to basics: searching for a comprehensive framework for exploring individual differences in zebrafish (Danio rerio) behavior. Zebrafish 11(4):325–340. https://doi.org/10.1089/zeb.2013.0952
Tsybko AS, Kondaurova EM, Zalivina EA, Blaginya VO, Naumenko VS (2023) Effects of chronic combined treatment with ketanserin and fluoxetine in B6. CBA-D13Mit76C recombinant mice with abnormal 5-HT1A receptor functional activity. Biochemistry (Moscow) 88(6):758–69. https://doi.org/10.1134/s0006297923060044
Ueno H, Takahashi Y, Suemitsu S, Murakami S, Kitamura N, Wani K, Matsumoto Y, Okamoto M, Ishihara T (2020) Caffeine inhalation effects on locomotor activity in mice. Drug Dev Ind Pharm 46(5):788–794. https://doi.org/10.1080/03639045.2020.1753064
Verma R, Choudhary PR, Nirmal NK, Syed F, Verma R (2022) Neurotransmitter systems in zebrafish model as a target for neurobehavioural studies. Mater Today: Proceedings 69:1565–1580. https://doi.org/10.1016/j.matpr.2022.07.147
Waldron AL, Schroder PA, Bourgon KL, Bolduc JK, Miller JL, Pellegrini AD, Dubois AL, Blaszkiewicz M, Townsend KL, Rieger S (2018) Oxidative stress-dependent MMP-13 activity underlies glucose neurotoxicity. J Diabetes Complications 32(3):249–257. https://doi.org/10.1016/j.jdiacomp.2017.11.012
Wang X, Zhang JB, He KJ, Wang F, Liu CF (2021) Advances of zebrafish in neurodegenerative disease: from models to drug discovery. Front Pharmacol 12:713963. https://doi.org/10.3389/fphar.2021.713963
Wang F, Ma X, Sun Q, Zhang Y, Liu Y, Gu J, Wang L (2023a) Bisphenol B induces developmental toxicity in zebrafish via oxidative stress. Environ Sci Pollut Res 11:1–1. https://doi.org/10.1007/s11356-023-31161-9
Wang L, Liu F, Fang Y, Ma J, Wang J, Qu L, Yang Q, Wu W, ** L, Sun D (2023b) Advances in zebrafish as a comprehensive model of mental disorders. Depress Anxiety 2023:1–48. https://doi.org/10.1155/2023/6663141
War R, Surendra V, Paul S, Sharma UR, Suresh J, Manjunatha PM (2022) Zebrafish as an emerging alternative tool for studying anxiety disorders. J Adv Sci Res 13(11):13–20. https://doi.org/10.55218/JASR.2022131103
Yue Q, Song Y, Liu Z, Zhang L, Yang L, Li J (2022) Receptor for advanced glycation end products (RAGE): a pivotal hub in immune diseases. Molecules 27(15):4922. https://doi.org/10.3390/molecules27154922
Zabegalov KN, Khatsko SL, Lakstygal AM, Demin KA, Cleal M, Fontana BD, McBride SD, Harvey BH, De Abreu MS, Parker MO, Kalueff AV (2019) Abnormal repetitive behaviors in zebrafish and their relevance to human brain disorders. Behav Brain Res 367:101–110. https://doi.org/10.1016/j.bbr.2019.03.044
Zhang Y, Li T, Pan C, Khan IA, Chen Z, Yue Y, Yang M (2022) Intergenerational toxic effects of parental exposure to bisphenol AF on offspring and epigenetic modulations in zebrafish. Sci Total Environ 823:153714. https://doi.org/10.1016/j.scitotenv.2022.153714
Zhang-James Y, Faraone SV (2016) Genetic architecture for human aggression: a study of gene–phenotype relationship in OMIM. Am J Med Genet B Neuropsychiatr Genet 171(5):641–649. https://doi.org/10.1002/ajmg.b.32363
Zonouzi-Marand M, Naderi M, Kwong RW (2022) Toxicological assessment of cadmium-containing quantum dots in develo** zebrafish: physiological performance and neurobehavioral responses. Aquat Toxicol 247:106157. https://doi.org/10.1016/j.aquatox.2022.106157
Author information
Authors and Affiliations
Contributions
Manuscript writing was performed by S.M.F., S. P., and S. K. S P. and F. Z. are involved in figure and table construction. S.M.F. and F. Z. are revising the manuscript to its definitive form. The authors confirm that no paper mill and artificial intelligence was used.
Corresponding author
Ethics declarations
Ethical approval
Not applicable.
Competing interests
The author has no potential conflict of interest with any groups.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Firdous, S.M., Pal, S., Khanam, S. et al. Behavioral neuroscience in zebrafish: unravelling the complexity of brain-behavior relationships. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03275-5
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00210-024-03275-5