scholarly journals Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid

2013 ◽  
Vol 16 (1) ◽  
pp. 91-103 ◽  
Author(s):  
Shunsuke Kataoka ◽  
Kazuhiro Takuma ◽  
Yuta Hara ◽  
Yuko Maeda ◽  
Yukio Ago ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Social Interaction ◽  
Prenatal Exposure ◽  
Apoptotic Cell ◽  
Autism Spectrum ◽  
Prenatally Exposed ◽  
Histone Deacetylase Inhibition ◽  
Histone Hyperacetylation ◽  
The Social ◽  
Cortical Pathology

Abstract Maternal use of valproic acid (VPA) during pregnancy has been implicated in the aetiology of autism spectrum disorders in children, and rodents prenatally exposed to VPA showed behavioural alterations similar to those observed in humans with autism. However, the exact mechanism for VPA-induced behavioural alterations is not known. To study this point, we examined the effects of prenatal exposure to VPA and valpromide, a VPA analog lacking histone deacetylase inhibition activity, on behaviours, cortical pathology and histone acetylation levels in mice. Mice exposed to VPA at embryonic day 12.5 (E12.5), but not at E9 and E14.5, displayed social interaction deficits, anxiety-like behaviour and memory deficits at age 4–8 wk. In contrast to male mice, the social interaction deficits (a decrease in sniffing behaviour) were not observed in female mice at age 8 wk. The exposure to VPA at E12.5 decreased the number of Nissl-positive cells in the middle and lower layers of the prefrontal cortex and in the lower layers of the somatosensory cortex at age 8 wk. Furthermore, VPA exposure caused a transient increase in acetylated histone levels in the embryonic brain, followed by an increase in apoptotic cell death in the neocortex and a decrease in cell proliferation in the ganglionic eminence. In contrast, prenatal exposure to valpromide at E12.5 did not affect the behavioural, biochemical and histological parameters. Furthermore, these findings suggest that VPA-induced histone hyperacetylation plays a key role in cortical pathology and abnormal autism-like behaviours in mice.

scholarly journals Psilocybin rescues sociability deficits in an animal model of autism

2020 ◽  
Author(s):  
Irene Mollinedo-Gajate ◽  
Chenchen Song ◽  
Marcos Sintes-Rodriguez ◽  
Tobias Whelan ◽  
Anaïs Soula ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Valproic Acid ◽  
Animal Model ◽  
Social Interaction ◽  
Mouse Model ◽  
Therapeutic Agent ◽  
Autism Spectrum ◽  
The Core ◽  
Acute Response ◽  
The Social

AbstractAutism spectrum disorder (ASD) is characterized by core deficits in social interaction. The classic serotonergic psychedelic psilocybin has been suggested as a therapeutic agent that may ameliorate in the core symptomology of ASD. We found that the acute response to psilocybin was attenuated in the prenatal valproic acid exposure mouse model of ASD, and importantly, psilocybin rescued the social behavioural abnormalities present in these ASD model mice.

scholarly journals Neonatal Exposure to Sevoflurane Induces Abnormal Social Behaviors and Deficits in Fear Conditioning in Mice

2009 ◽  
Vol 110 (3) ◽  
pp. 628-637 ◽  
Author(s):  
Maiko Satomoto ◽  
Yasushi Satoh ◽  
Katsuo Terui ◽  
Hideki Miyao ◽  
Kunio Takishima ◽  
...  
Keyword(s):  
Social Interaction ◽  
Social Behavior ◽  
Fear Conditioning ◽  
Social Behaviors ◽  
Autism Spectrum ◽  
Social Recognition ◽  
Neonatal Exposure ◽  
Learning Deficits ◽  
Neonatal Mice ◽  
The Social

Background Neonatal exposure to anesthetics that block N-methyl-D-aspartate receptors and/or hyperactivate gamma-aminobutyric acid type A receptor has been shown to cause neuronal degeneration in the developing brain, leading to functional deficits later in adulthood. The authors investigated whether exposure of neonatal mice to inhaled sevoflurane causes deficits in social behavior as well as learning disabilities. Methods Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h. Activated cleaved caspase-3 immunohistochemical staining was used for detection of apoptosis. Cognitive functions were tested by pavlovian conditioned fear test. Social behavior was tested by social recognition and interaction tests. Results Neonatal exposure to sevoflurane significantly increased the number of apoptotic cells in the brain immediately after anesthesia. It caused persistent learning deficits later in adulthood as evidenced by decreased freezing response in both contextual and cued fear conditioning. The social recognition test demonstrated that mice with neonatal exposure to sevoflurane did not develop social memory. Furthermore, these mice showed decreased interactions with a social target compared with controls in the social interaction test, indicating a social interaction deficit. The authors did not attribute these abnormalities in social behavior to impairments of general interest in novelty or olfactory sensation, because they did not detect significant differences in the test for novel inanimate object interaction or for olfaction. Conclusions This study shows that exposure of neonatal mice to inhaled sevoflurane could cause not only learning deficits but also abnormal social behaviors resembling autism spectrum disorder.

scholarly journals Pentylenetetrazole-induced seizures in developing rats prenatally exposed to valproic acid

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2709
Author(s):  
Angel A. Puig-Lagunes ◽  
Jorge Manzo ◽  
Luis Beltrán-Parrazal ◽  
Consuelo Morgado-Valle ◽  
Rebeca Toledo-Cárdenas ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Clonic Seizure ◽  
Autism Spectrum ◽  
Seizure Susceptibility ◽  
Prenatally Exposed ◽  
Seizure Severity ◽  
Pregnant Females ◽  
Rat Pups ◽  
Spectrum Disorders ◽  
And Control

Background Epidemiological evidence indicates epilepsy is more common in patients with autism spectrum disorders (ASD) (20–25%) than in the general population. The aim of this project was to analyze seizure susceptibility in developing rats prenatally exposed to valproic acid (VPA) as autism model. Methods Pregnant females were injected with VPA during the twelfth embryonic day. Seizures were induced in fourteen-days-old rat pups using two models of convulsions: pentylenetetrazole (PTZ) and lithium-pilocarpine (Li-Pilo). Results Two subgroups with different PTZ-induced seizure susceptibility in rats exposed to VPA were found: a high susceptibility (VPA+) (28/42, seizure severity 5) and a low susceptibility (VPA−) (14/42, seizure severity 2). The VPA+ subgroup exhibited an increased duration of the generalized tonic-clonic seizure (GTCS; 45 ± 2.7 min), a higher number of rats showed several GTCS (14/28) and developed status epilepticus (SE) after PTZ injection (19/27) compared with control animals (36.6 ± 1.9 min; 10/39; 15/39, respectively). No differences in seizure severity, latency or duration of SE induced by Li-Pilo were detected between VPA and control animals. Discussion Prenatal VPA modifies the susceptibility to PTZ-induced seizures in developing rats, which may be linked to an alteration in the GABAergic transmission. These findings contribute to a better understanding of the comorbidity between autism and epilepsy.

A Naturalistic Behavioral Intervention to Increase Interaction between Siblings with and without Autism

2020 ◽  
pp. 014544552092081
Author(s):  
Laci Watkins ◽  
Theodore Tomeny ◽  
Mark O’Reilly ◽  
Katherine H. Sillis ◽  
Claudia Zamora
Keyword(s):  
Social Interaction ◽  
Autism Spectrum ◽  
Future Research ◽  
Typically Developing ◽  
Intervention Package ◽  
Adult Instruction ◽  
The Social ◽  
Reversal Design ◽  
High Level ◽  
Typically Developing Sibling

Research suggests that including typically developing siblings in interventions for children with autism spectrum disorder (ASD) may be beneficial. However, studies have predominantly involved only participants with mild symptoms of ASD and have not also reported outcomes for the typically developing sibling. The purpose of this study was to address these gaps by replicating and extending an intervention package consisting of structured, interest-based play activities, adult instruction and modeling, and response to child questions. A reversal design across two sibling dyads was used to demonstrate the effects of the intervention on the social interaction behaviors of the child with ASD and typically developing sibling. Social interaction increased for both sibling dyads, results generalized for one dyad, and multiple measures indicated a high level of social validity. Recommendations for practitioners and caregivers working with children with ASD and potential areas of future research are discussed.

scholarly journals Similarities between the Effects of Prenatal Chlorpyrifos and Valproic Acid on Ultrasonic Vocalization in Infant Wistar Rats

2020 ◽  
Vol 17 (17) ◽  
pp. 6376
Author(s):  
Miguel Morales-Navas ◽  
Sergio Castaño-Castaño ◽  
Cristian Pérez-Fernández ◽  
Ainhoa Sánchez-Gil ◽  
María Teresa Colomina ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Prenatal Exposure ◽  
High Frequency ◽  
Wistar Rats ◽  
Autism Spectrum ◽  
Emotional States ◽  
Good Tool ◽  
High Frequency Peak ◽  
Frequency Peak ◽  
Dependent Variables

Background: In recent years, ultrasonic vocalizations (USV) in pups has become established as a good tool for evaluating behaviors related to communication deficits and emotional states observed in autism spectrum disorder (ASD). Prenatal valproic acid (VPA) exposure leads to impairments and social behavior deficits associated with autism, with the effects of VPA being considered as a reliable animal model of ASD. Some studies also suggest that prenatal exposure to chlorpyrifos (CPF) could enhance autistic-like behaviors. Methods: In order to explore these similarities, in the present study we tested whether prenatal exposure to CPF at GD12.5–14.5 produces effects that are comparable to those produced by prenatal VPA exposure at GD12.5 in infant Wistar rats. Using Deep Squeek software, we evaluated total number of USVs, latency to the first call, mean call duration, principal frequency peak, high frequency peak, and type of calls. Results: Consistent with our hypothesis, we found that exposure to both CPF and VPA leads to a significantly smaller number of calls along with a longer latency to produce the first call. No significant effects were found for the remaining dependent variables. Conclusions: These results suggest that prenatal exposure to CPF could produce certain behaviors that are reminiscent of those observed in ASD patients.

scholarly journals Prenatal Exposure to Valproic Acid Affects Microglia and Synaptic Ultrastructure in a Brain-Region-Specific Manner in Young-Adult Male Rats: Relevance to Autism Spectrum Disorders

2020 ◽  
Vol 21 (10) ◽  
pp. 3576 ◽  
Author(s):  
Magdalena Gąssowska-Dobrowolska ◽  
Magdalena Cieślik ◽  
Grzegorz Arkadiusz Czapski ◽  
Henryk Jęśko ◽  
Małgorzata Frontczak-Baniewicz ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Autism Spectrum Disorders ◽  
Young Adult ◽  
Prenatal Exposure ◽  
Adult Male ◽  
Brain Region ◽  
Autism Spectrum ◽  
Synaptic Proteins ◽  
Specific Manner ◽  
Spectrum Disorders

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental conditions categorized as synaptopathies. Environmental risk factors contribute to ASD aetiology. In particular, prenatal exposure to the anti-epileptic drug valproic acid (VPA) may increase the risk of autism. In the present study, we investigated the effect of prenatal exposure to VPA on the synaptic morphology and expression of key synaptic proteins in the hippocampus and cerebral cortex of young-adult male offspring. To characterize the VPA-induced autism model, behavioural outcomes, microglia-related neuroinflammation, and oxidative stress were analysed. Our data showed that prenatal exposure to VPA impaired communication in neonatal rats, reduced their exploratory activity, and led to anxiety-like and repetitive behaviours in the young-adult animals. VPA-induced pathological alterations in the ultrastructures of synapses accompanied by deregulation of key pre- and postsynaptic structural and functional proteins. Moreover, VPA exposure altered the redox status and expression of proinflammatory genes in a brain region-specific manner. The disruption of synaptic structure and plasticity may be the primary insult responsible for autism-related behaviour in the offspring. The vulnerability of specific synaptic proteins to the epigenetic effects of VPA may highlight the potential mechanisms by which prenatal VPA exposure generates behavioural changes.

scholarly journals Virtual Voice Assistant Applications Improved Expressive Verbal Abilities and Social Interactions in Children with Autism Spectrum Disorder: A Single-Subject Experimental Study

2021 ◽  
Author(s):  
Mohammed F Safi ◽  
Badriya Al Sadrani ◽  
Ashraf Mustafa
Keyword(s):  
Artificial Intelligence ◽  
Social Interaction ◽  
Social Interactions ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Baseline Phase ◽  
Children With Asd ◽  
The Social ◽  
Social Interaction Skills ◽  
Interaction Skills

Abstract Background: Children with autism spectrum disorder (ASD) tend to have communication and social interaction deficits. Their impaired communication is derived from difficulties in acquiring language. The use of interactive technologies has been demonstrated to enhance verbal and non-verbal communication, as well as the social interaction tendencies of children with ASD. Artificial intelligence has played a growing role in the habilitation of children with ASD. However, little research exists on the possible roles and effectiveness of virtual voice assistants in developing language and social skills in children with ASD. This study examined the effects of using a voice assistant in children with ASD on two outcomes: speech skills (expressive verbal vocabulary and production of short phrases) and social interaction skills (playing/sharing). Methods: An interventional single-case design study was used to explore this concept using three children with ASD between the ages of 4 and 11 years. The participants used an accessible virtual voice assistant, Apple’s Siri, for three months. Pre- and post-intervention questionnaires and semi-structured interviews with mothers were administered to measure the communication and social interaction skills of the participating children. Results: Participant One, Two and Three showed a notable improvement in the total number of correct words produced with fewer attempts during the VVA intervention compared with the baseline phase. Further, all participants showed increases in the social interactions in the intervention phase, compared with the baseline phase. Finally, all the mothers noted improvement in their children’s speech intelligibility and social interactions. Conclusions: Results showed that the virtual voice assistant had positive effects on the speech and social interaction skills of children with ASD. The findings of this study implied that children with ASD can use readily available voice assistant software to improve their speech and social interaction skills. Furthermore, this study’s findings could be used to develop strategies to increase the availability of artificial intelligence infrastructure in schools and homes to help children with ASD.

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