Hyperactivation of the amygdala correlates with impaired social play behavior of prepubertal male rats in a maternal immune activation model

Vitor-Vieira, Fernando; Giusti‐Paiva, Alexandre

doi:10.1016/j.bbr.2021.113503

Cited by 18 publications

(8 citation statements)

References 96 publications

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“…As a hub in the "social brain, " the amygdala, which was located within the anterior medial portion of the brain's temporal lobe, maintains diverse connections with the neocortex, basal ganglia, hippocampus, thalamus, and other brain cortical areas via a network of white matter tracts, responsible for information processing that subserve emotional learning, social cognition, and social interaction (Baron-Cohen et al, 2000;Zalla and Sperduti, 2013;Ferrara et al, 2021;Raam and Hong, 2021;Xu et al, 2021). A large number of studies have demonstrated that amygdala structural and/or functional abnormalities are associated with social malfunctioning in ASD (Shen et al, 2016;Avino et al, 2018;Herrero et al, 2020;Xu et al, 2020;Seguin et al, 2021;Vitor-Vieira et al, 2021). So, we speculated that the prosocial behavior of AVP may be related to the amygdala.…”

Section: Discussionmentioning

confidence: 99%

The Changes of Amygdala Transcriptome in Autism Rat Model After Arginine Vasopressin Treatment

et al. 2022

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BackgroundSome studies have shown that arginine vasopressin (AVP) can significantly improve the social interaction disorder of autism, but the mechanism remains unclear.MethodsFemale Wistar rats were intraperitoneally injected with VPA or normal saline at embryonic day 12.5 to establish an autism model or normal control in their offspring. Male offspring prenatally exposed to VPA were randomly assigned to two groups: the VPA-induced autism model group and the AVP group. The rats in the AVP group were treated with intranasal AVP at postnatal day (PND) 21 and for 3 weeks. The VPA-induced autism model group was given the same dose of normal saline in the same way. Behavioral responses were evaluated in the open field and three-chambered social test apparatus; the expression levels of AVP in serum were detected by enzyme-linked immunosorbent assay kit, and the gene expression levels on the amygdala were measured by RNA-seq at PND42.ResultsIntranasal administration of AVP can significantly improve the social interaction disorder and elevate the levels of AVP in serum. Transcriptome sequencing results showed that 518 differently expressed genes (DEGs) were identified in the VPA-induced autism model group compared with the control in this study. Gene Ontology biological process enrichment analysis of DEGs showed that the VPA-induced autism model group had significant nervous system developmental impairments compared with the normal group, particularly in gliogenesis, glial cell differentiation, and oligodendrocyte differentiation. Gene Set Enrichment Analysis (GSEA) enrichment analysis also showed that biological process of oligodendrocyte differentiation, axoneme assembly, and axon ensheathment were inhibited in the VPA-induced autism model group. Pathway enrichment analysis of DEGs between the control and VPA-induced autism model group showed that the PI3K/AKT and Wnt pathways were significantly dysregulated in the VPA-induced autism model group. Few DEGs were found when compared with the transcriptome between the VPA-induced autism model group and the AVP treatment group. GSEA enrichment analysis showed deficits in oligodendrocyte development and function were significantly improved after AVP treatment; the pathways were mainly enriched in the NOTCH, mitogen-activated protein kinase, and focal adhesion signaling pathways, but not in the PI3K/AKT and Wnt pathways. The expression patterns analysis also showed the same results.ConclusionAVP can significantly improve the social interaction disorder of VPA-induced autism model, and AVP may target behavioral symptoms in autism by modulating the vasopressin pathways, rather than primary disease mechanisms.

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Section: Discussionmentioning

confidence: 99%

The Changes of Amygdala Transcriptome in Autism Rat Model After Arginine Vasopressin Treatment

et al. 2022

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“…One reason for the lack of effect on USV numbers could be the timepoint of MIA induction. Another study that also induced MIA on GD9.5 saw also no change in USV numbers, 38 whereas other studies with MIA induction on a later GD found decreased USV numbers (GD15‐16 35–37,39 ).…”

Section: Discussionmentioning

confidence: 95%

Characterizing maternal isolation‐induced ultrasonic vocalizations in a gene–environment interaction rat model for autism

Möhrle

Yuen

Zheng

et al. 2023

Genes Brain and Behavior

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Deficits in social communication and language development belong to the earliest diagnostic criteria of autism spectrum disorders. Of the many risk factors for autism spectrum disorder, the contactin-associated protein-like 2 gene, CNTNAP2, is thought to be important for language development. The present study used a rat model to investigate the potential compounding effects of autism spectrum disorder risk gene mutation and environmental challenges, including breeding conditions or maternal immune activation during pregnancy, on early vocal communication in the offspring.Maternal isolation-induced ultrasonic vocalizations from Cntnap2 wildtype and knockout rats at selected postnatal days were analyzed for their acoustic, temporal and syntax characteristics. Cntnap2 knockout pups from heterozygous breeding showed normal numbers and largely similar temporal structures of ultrasonic vocalizations to wildtype controls, whereas both parameters were affected in homozygously bred knockouts. Homozygous breeding further exacerbated altered pitch and transitioning between call types found in Cntnap2 knockout pups from heterozygous breeding. In contrast, the effect of maternal immune activation on the offspring's vocal communication was confined to call type syntax, but left ultrasonic vocalization acoustic and temporal organization intact. Our results support the "double-hit hypothesis" of autism spectrum disorder risk gene-environment interactions and emphasize that complex features of vocal communication are a useful tool for identifying early autistic-like features in rodent models.

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“…Social play interactions in rodents help guide the practice of behaviors in a mock form that will later form part of the adult behavioral repertoire. When prepubertal rats are placed together in a non‐threatening environment, they rapidly begin to exhibit social play interaction in that animal's chase and sniff on each other (Carvalho et al, 2016); Vitor‐Vieira et al, 2021). Social play is thought to be important for the development of social, cognitive, and emotional processes, and it is disrupted in pediatric psychiatric disorders (Achterberg & Trezza, 2017).…”

Section: Discussionmentioning

confidence: 99%

Perinatal exposure to glyphosate‐based herbicides induced neurodevelopmental behaviors impairments and increased oxidative stress in the prefrontal cortex and hippocampus in offspring

Oliveira

Rojas

Sá

et al. 2022

Intl J of Devlp Neuroscience

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Glyphosate is the organophosphate pesticide most widely used in the world. Recent studies correlate exposure to glyphosate and the emergence of neurodevelopmental disorders. Therefore, it was objective to propose a rat model of perinatal exposure to glyphosate-based herbicides (GBH) to study associated neurodevelopmental disorders. Behavioral aspects and brain pathways were assessed in the prepubertal phase. For this, maternal treatment occurred throughout the entire gestation period (from GD0) until weaning on postnatal day 22 (PND 22). Control group received oral gavage with 5 mL/kg of saline per day and GBH group received oral gavage with 50 mg/kg of GBH per day (n = 10 per group). Maternal behavior was evaluated in PND 2-6. Offspring were evaluated for quantification of ultrasonic vocalizations (PND 5); homing behavior test (PND 13); and hole board, social play behavior, open field, and object recognition tests . Prefrontal cortex and hippocampus of the offspring were processed to evaluate oxidative stress. Maternal exposure to GBH impaired early social communication, olfactory discrimination, social play behavior, and the exploration of objects, in addition to increasing repetitive and stereotyped movements. GBH also increased oxidative stress. Therefore, perinatal GBH exposure induced behavioral and oxidative stress impairments in rats associated with neurodevelopmental disorders. The manifestations found in the offspring are in accordance with symptoms of autism spectrum disorder.

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Hyperactivation of the amygdala correlates with impaired social play behavior of prepubertal male rats in a maternal immune activation model

Cited by 18 publications

References 96 publications

The Changes of Amygdala Transcriptome in Autism Rat Model After Arginine Vasopressin Treatment

The Changes of Amygdala Transcriptome in Autism Rat Model After Arginine Vasopressin Treatment

Characterizing maternal isolation‐induced ultrasonic vocalizations in a gene–environment interaction rat model for autism

Perinatal exposure to glyphosate‐based herbicides induced neurodevelopmental behaviors impairments and increased oxidative stress in the prefrontal cortex and hippocampus in offspring

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