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Autism-associated gene shank3 is necessary for social contagion in zebrafish

2023Journal article Open access
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dc.contributor.authorKareklas, Kyriacos
dc.contributor.authorTeles, Magda C
dc.contributor.authorDreosti, Elena
dc.contributor.authorOliveira, Rui F.
dc.date.accessioned2024-02-22T17:55:40Z
dc.date.available2024-02-22T17:55:40Z
dc.date.issued2023
dc.description.abstractBackground Animal models enable targeting autism-associated genes, such as the shank3 gene, to assess their impact on behavioural phenotypes. However, this is often limited to simple behaviours relevant for social interaction. Social contagion is a complex phenotype forming the basis of human empathic behaviour and involves attention to the behaviour of others for recognizing and sharing their emotional or affective state. Thus, it is a form of social communication, which constitutes the most common developmental impairment across autism spectrum disorders (ASD). Methods Here we describe the development of a zebrafish model that identifies the neurocognitive mechanisms by which shank3 mutation drives deficits in social contagion. We used a CRISPR-Cas9 technique to generate mutations to the shank3a gene, a zebrafish paralogue found to present greater orthology and functional conservation relative to the human gene. Mutants were first compared to wild types during a two-phase protocol that involves the observation of two conflicting states, distress and neutral, and the later recall and discrimination of others when no longer presenting such differences. Then, the whole-brain expression of different neuroplasticity markers was compared between genotypes and their contribution to cluster-specific phenotypic variation was assessed. Results The shank3 mutation markedly reduced social contagion via deficits in attention contributing to difficulties in recognising affective states. Also, the mutation changed the expression of neuronal plasticity genes. However, only downregulated neuroligins clustered with shank3a expression under a combined synaptogenesis component that contributed specifically to variation in attention. Limitations While zebrafish are extremely useful in identifying the role of shank3 mutations to composite social behaviour, they are unlikely to represent the full complexity of socio-cognitive and communication deficits presented by human ASD pathology. Moreover, zebrafish cannot represent the scaling up of these deficits to higher-order empathic and prosocial phenotypes seen in humans. Conclusions We demonstrate a causal link between the zebrafish orthologue of an ASD-associated gene and the attentional control of affect recognition and consequent social contagion. This models autistic affect-communication pathology in zebrafish and reveals a genetic attention-deficit mechanism, addressing the ongoing debate for such mechanisms accounting for emotion recognition difficulties in autistic individuals.pt_PT
dc.description.sponsorshipFundação para a Ciência e Tecnologia- FCT; FEDERpt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationKareklas, K., Teles, M. C., Dreosti, E., & Oliveira, R. F. (2023). Autism-associated gene shank3 is necessary for social contagion in zebrafish. Molecular Autism, 14(1), 1–15. https://doi.org/10.1186/s13229-023-00555-4pt_PT
dc.identifier.doi10.1186/s13229-023-00555-4pt_PT
dc.identifier.issn20402392
dc.identifier.urihttp://hdl.handle.net/10400.12/9600
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBioMed Central Ltd.pt_PT
dc.relationPTDC/BIA-COM/3068/2020pt_PT
dc.relationLISBOA-01-0145-FEDER-022170,pt_PT
dc.subjectAutismpt_PT
dc.subjectSHANK3pt_PT
dc.subjectSocial contagionpt_PT
dc.subjectZebrafish,pt_PT
dc.subjectAffectpt_PT
dc.subjectRecognitionpt_PT
dc.subjectAttentionpt_PT
dc.subjectNeuroplasticitypt_PT
dc.subjectSynaptogenesispt_PT
dc.subjectNeuroliginspt_PT
dc.titleAutism-associated gene shank3 is necessary for social contagion in zebrafishpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceUnited Kingdompt_PT
oaire.citation.issue1pt_PT
oaire.citation.titleMolecular Autismpt_PT
oaire.citation.volume14pt_PT
person.familyNameKareklas
person.familyNameTeles
person.familyNameDreosti
person.familyNameOliveira
person.givenNameKyriacos
person.givenNameMagda C
person.givenNameElena
person.givenNameRui
person.identifier.ciencia-idE81E-61AE-44BC
person.identifier.ciencia-id611C-50AD-6CE7
person.identifier.orcid0000-0003-2453-9556
person.identifier.orcid0000-0002-3051-8332
person.identifier.orcid0000-0002-6738-7057
person.identifier.orcid0000-0003-1528-618X
person.identifier.ridA-3581-2013
person.identifier.scopus-author-id16200314100
person.identifier.scopus-author-id35561080400
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationdcba9b58-8e19-4d94-a75b-a9d162d09985
relation.isAuthorOfPublication56a9d10c-8d25-4635-a714-03a0eda7fcd4
relation.isAuthorOfPublication841780ba-2976-4c38-8976-41d5f710c434
relation.isAuthorOfPublication52f01205-dce9-433b-85c5-6390488b1eee
relation.isAuthorOfPublication.latestForDiscoverydcba9b58-8e19-4d94-a75b-a9d162d09985

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