# Oxytocinergic Signaling in Zebrafish: Translational Perspectives for Autism Spectrum Disorder

**Authors:** Géssica Peres, Melissa Talita Wiprich, Darlan Gusso, Carla Denise Bonan

PMC · DOI: 10.1111/jnc.70346 · 2026-01-13

## TL;DR

This paper explores how oxytocin signaling in zebrafish can help understand and model autism spectrum disorder.

## Contribution

The paper highlights zebrafish as a translational model for studying oxytocin-related mechanisms in autism.

## Key findings

- Zebrafish have conserved oxytocin pathways and complex social behaviors, making them suitable for ASD modeling.
- Oxytocin signaling alterations are strongly linked to social and cognitive deficits in neurodevelopmental disorders.

## Abstract

Alterations in the oxytocin system, accompanied by cognitive and behavioral deficits, are common in several neurodevelopmental conditions, including Autism Spectrum Disorder. Oxytocin, a neuropeptide produced in the hypothalamus, plays a pivotal role in modulating social cognition and complex social behaviors. Recently, increasing attention has been given to the therapeutic potential of oxytocin in the treatment of neurodevelopmental disorders. However, many aspects of oxytocin signaling and its effects remain to be fully elucidated. Given its pronounced social behaviors and conserved neurochemical pathways, the zebrafish (
Danio rerio
) has emerged as a model for investigating the neural and behavioral effects of oxytocin. This species exhibits a wide behavioral repertoire, making it suitable for modeling oxytocin‐related neurodevelopmental alterations. Here we provide an overview of the key mechanisms underlying oxytocin signaling and discuss current findings supporting the use of zebrafish as an Autism Spectrum Disorder model.

Alterations in oxytocin signaling are strongly implicated in the social and cognitive deficits characterizing Autism Spectrum Disorder (ASD) and other neurodevelopmental conditions. However, the precise mechanisms remain unclear. The zebrafish (
Danio rerio
) has emerged as a powerful translational model due to its evolutionarily conserved oxytocin pathways and rich repertoire of complex social behaviors. This review synthesizes key mechanisms of oxytocin signaling and evaluates the evidence supporting the use of zebrafish to model ASD and elucidate these critical pathways.

## Linked entities

- **Diseases:** Autism Spectrum Disorder (MONDO:0005258)
- **Species:** Danio rerio (taxon 7955)

## Full-text entities

- **Genes:** shank3a (SH3 and multiple ankyrin repeat domains 3a) [NCBI Gene 557701] {aka si:dkeyp-1h4.1, zs3.2}, adsl (adenylosuccinate lyase) [NCBI Gene 334431] {aka fi60b04, wu:fi60b04, zgc:56061}, cntnap2b (contactin associated protein 2b) [NCBI Gene 563345] {aka Caspr2b, cntnap2, si:ch211-120f16.4}, oxtrb (oxytocin receptor b) [NCBI Gene 796298] {aka oxtrl}, OXT (oxytocin/neurophysin I prepropeptide) [NCBI Gene 5020] {aka OT, OT-NPI, OXT-NPI}, cntnap2a (contactin associated protein 2a) [NCBI Gene 559157] {aka Caspr2a}, esr1 (estrogen receptor 1) [NCBI Gene 259252] {aka ER[a], ESR, NR3A1, abrrl, eralpha, zfER[a]}, dyrk1aa (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A, a) [NCBI Gene 100005019] {aka dyrk1a, im:6962097, zgc:158359}, SHANK3 [NCBI Gene 793484], shank3b (SH3 and multiple ankyrin repeat domains 3b) [NCBI Gene 566152] {aka shank3, si:dkey-153k10.1}, oxt (oxytocin) [NCBI Gene 352920] {aka IT-NP, fj33a01, ist, itnp, oxtl, wu:fj33a01}, oxtra (oxytocin receptor a) [NCBI Gene 100001530] {aka oxtr}
- **Diseases:** schizophrenia (MESH:D012559), social impairments (OMIM:300082), Visual or sensorimotor integration deficits (MESH:D014786), VT (MESH:D006555), social disorders (MESH:D000067404), Impairments in social recognition (MESH:D020238), aggression (MESH:D010554), Mental Disorders (MESH:D001523), epilepsy (MESH:D004827), ASD (MESH:D000067877), NDDs (MESH:D002658), impulsivity (MESH:D007174), OMR deficits (MESH:D009461), cognitive and behavioral deficits (MESH:D003072), Prader-Willi syndrome (MESH:D011218), impairments in learning and memory (MESH:D007859), behavioral deficits (MESH:D019958), pain (MESH:D010146), anxiety (MESH:D001007), deficits in social interaction and communication (MESH:D003147), intellectual disability (MESH:D008607), Asperger (MESH:D020817), mood disorders (MESH:D019964), autism (MESH:D001321), empathy impairments (MESH:D060825)
- **Chemicals:** VPA (MESH:D014635), Isotocin (MESH:C008215), E2 (MESH:D004958), PAG (-), endocannabinoid (MESH:D063388), Carbetocin (MESH:C020731), arginine-vasotocin (MESH:D014668), MK-801 (MESH:D016291), OT (MESH:C013307), L-368899 (MESH:C086206), Poly(I:C) (MESH:D011070), WAY-267464 (MESH:C547280), noradrenaline (MESH:D009638)
- **Species:** Danio rerio (leopard danio, species) [taxon 7955], Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12797022/full.md

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Source: https://tomesphere.com/paper/PMC12797022