Rescue of oxytocin response and social behaviour in a mouse model of autism

Hörnberg, Hanna; Pérez-Garci, Enrique; Schreiner, Dietmar; Hatstatt-Burklé, Laetitia; Magara, Fulvio; Baudouin, Stéphane J.; Matter, Alex; Nacro, Kassoum; Pecho-Vrieseling, Eline; Scheiffele, Peter

doi:10.1038/s41586-020-2563-7

Cited by 99 publications

(95 citation statements)

References 63 publications

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“…The change in social behavior was dependent on an intact vagus nerve and absent in animals lacking the oxytocin receptor in dopaminergic neurons of the ventral tegmental area (Sgritta et al 2019). Also, restoration of oxytocin-signaling in the dopaminergic neurons rescued social novelty responses in Nlgn3mice (Hörnberg et al 2020). These examples from animal experiments show that oxytocin can increase sociability and social cognition across different genetic ASD models.…”

Section: Neural Processing Of Social Odors In Asd Models and Patientsmentioning

confidence: 82%

Genetic influences of autism candidate genes on circuit wiring and olfactory decoding

et al. 2021

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Olfaction supports a multitude of behaviors vital for social communication and interactions between conspecifics. Intact sensory processing is contingent upon proper circuit wiring. Disturbances in genetic factors controlling circuit assembly and synaptic wiring can lead to neurodevelopmental disorders, such as autism spectrum disorder (ASD), where impaired social interactions and communication are core symptoms. The variability in behavioral phenotype expression is also contingent upon the role environmental factors play in defining genetic expression. Considering the prevailing clinical diagnosis of ASD, research on therapeutic targets for autism is essential. Behavioral impairments may be identified along a range of increasingly complex social tasks. Hence, the assessment of social behavior and communication is progressing towards more ethologically relevant tasks. Garnering a more accurate understanding of social processing deficits in the sensory domain may greatly contribute to the development of therapeutic targets. With that framework, studies have found a viable link between social behaviors, circuit wiring, and altered neuronal coding related to the processing of salient social stimuli. Here, the relationship between social odor processing in rodents and humans is examined in the context of health and ASD, with special consideration for how genetic expression and neuronal connectivity may regulate behavioral phenotypes.

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Section: Neural Processing Of Social Odors In Asd Models and Patientsmentioning

confidence: 82%

Genetic influences of autism candidate genes on circuit wiring and olfactory decoding

et al. 2021

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“…Oxytocin deficiency, present in the Magel2-KO mouse model and in PWS, has also been frequently described in rodent models of ASD (2). Recently, evidences for a unifying role of oxytocin in pathogenic mechanisms responsible for social impairments across abroad range of autism etiologies have been provided (67, 68). Thus, our results demonstrate that peripheral OT-administration in a critical period of time, after birth, represents a viable therapeutic strategy for patients with SYS or PWS and possibly other neurodevelopmental disorders.…”

Section: Discussionmentioning

confidence: 99%

Oxytocin administration in neonates shapes the hippocampal circuitry and restores social behavior in a mouse model of autism

Bertoni

Schaller

Tyzio

et al. 2020

Preprint

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Several studies on rodent models with an Autism Spectrum Disorders-like (ASD) phenotype, notably Magel2-deficient mice, have shown a rescue of deficits in adult social behavior after neonatal administration of oxytocin. However, the neurobiological alterations responsible for the social deficits and the mechanism by which oxytocin-administration in infancy has a rescue effect in adulthood remain unclear.Here we show that Magel2-deficient adult mice exhibit a deficit in social memory that is corrected by neonatal oxytocin administration. We studied hippocampal regions known to be associated with social memory engrams involving the OT-system. At critical stages of development, we characterized cellular, physiological and biochemical alterations of these hippocampal regions in Magel2-deficient mice, alterations present in several ASD models. Overall we demonstrate a strong impact of oxytocin-administration at key stages of postnatal hippocampal neurodevelopment, shedding light on the role for oxytocin in treating neurodevelopmental disorders characterized by deficits in social memory.

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“…In addition, several links have been made between oxytocin signaling and autism spectrum disorder. In two different mice models, mutations in human autism risk genes resulted in impaired oxytocin signaling and autistic-like behavior [ 91 , 92 ].…”

Section: Resultsmentioning

confidence: 99%

Effects of air pollution exposure on social behavior: a synthesis and call for research

Weitekamp

Hofmann

2021

Environ Health

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Background There is a growing literature from both epidemiologic and experimental animal studies suggesting that exposure to air pollution can lead to neurodevelopmental and neuropsychiatric disorders. Here, we suggest that effects of air pollutant exposure on the brain may be even broader, with the potential to affect social decision-making in general. Methods We discuss how the neurobiological substrates of social behavior are vulnerable to air pollution, then briefly present studies that examine the effects of air pollutant exposure on social behavior-related outcomes. Results Few experimental studies have investigated the effects of air pollution on social behavior and those that have focus on standard laboratory tests in rodent model systems. Nonetheless, there is sufficient evidence to support a critical need for more research. Conclusion For future research, we suggest a comparative approach that utilizes diverse model systems to probe the effects of air pollution on a wider range of social behaviors, brain regions, and neurochemical pathways.

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Rescue of oxytocin response and social behaviour in a mouse model of autism

Abstract: Chadman, K. K. et al. Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice.

Cited by 99 publications

References 63 publications

Genetic influences of autism candidate genes on circuit wiring and olfactory decoding

Genetic influences of autism candidate genes on circuit wiring and olfactory decoding

Oxytocin administration in neonates shapes the hippocampal circuitry and restores social behavior in a mouse model of autism

Effects of air pollution exposure on social behavior: a synthesis and call for research

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