Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice

Yamaguchi, Hiroshi; Hara, Yuta; Ago, Yukio; Takano, Erika; Hasebe, Shigeru; Nakazawa, Takahiro; Hashimoto, Hitoshi; Matsuda, Takehisa; Takuma, Kazuhiro

doi:10.1016/j.bbr.2017.06.035

Cited by 71 publications

(61 citation statements)

References 44 publications

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“…VPA males displayed reduced rearing in the cylinder test, increased immobility, and reduced locomotor activity in the SHIRPA arena. This is in line with previous findings obtained in older animals showing reduced locomotor activity following prenatal VPA treatment (Kataoka et al, 2013; Yamaguchi et al, 2017) and with clinical studies showing that children with ASD spend less time actively exploring their environment (Pierce and Courchesne, 2001). …”

Section: Discussionsupporting

confidence: 92%

Motor Impairments Correlate with Social Deficits and Restricted Neuronal Loss in an Environmental Model of Autism

Sagheer

Haïda

Balbous

et al. 2018

International Journal of Neuropsychopharmacology

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BackgroundMotor impairments are amongst the earliest and most consistent signs of autism spectrum disorders but are not used as diagnostic criteria. In addition, the relationship between motor and cognitive impairments and their respective neural substrates remain unknown.MethodsHere, we aimed at determining whether a well-acknowledged animal model of autism spectrum disorders, the valproic acid model, displays motor impairments and whether they may correlate with social deficits and neuronal loss within motor brain areas. For this, pregnant female mice (C57BL/6J) received valproic acid (450 mg/kg) at embryonic day 12.5 and offspring underwent a battery of behavioral analyses before being killed for histological correlates in motor cortex, nigrostriatal pathway, and cerebellum.ResultsWe show that while valproic acid male mice show both social and motor impairments, female mice only show motor impairments. Prenatal valproic acid exposure induces specific cell loss within the motor cortex and cerebellum and that is of higher magnitude in males than in females. Finally, we demonstrate that motor dysfunction correlates with reduced social behavior and that motor and social deficits both correlate with a loss of Purkinje cells within the Crus I cerebellar area.ConclusionsOur results suggest that motor dysfunction could contribute to social and communication deficits in autism spectrum disorders and that motor and social deficits may share common neuronal substrates in the cerebellum. A systematic assessment of motor function in autism spectrum disorders may potentially help the quantitative diagnosis of autism spectrum disorders and strategies aimed at improving motor behavior may provide a global therapeutic benefit.

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Section: Discussionsupporting

confidence: 92%

Motor Impairments Correlate with Social Deficits and Restricted Neuronal Loss in an Environmental Model of Autism

Sagheer

Haïda

Balbous

et al. 2018

International Journal of Neuropsychopharmacology

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“…Our results indicate that raising Shank3 mutant mice in enriched environments has little effect on their behavior, which is somewhat surprising, given that environmental enrichment has been shown to alleviate behavioral phenotypes in a number of other rodent models of ASDs (Favre et al, ; Garbugino et al, ; Kerr et al, ; Kondo et al, ; Lacaria et al, ; Lonetti et al, ; Nag et al, ; Oddi et al, ; Restivo et al, ; Reynolds et al, ; Schneider et al, ; Yamaguchi et al, ). A summary of previous findings along with findings from the current study is provided in Table .…”

Section: Discussionmentioning

confidence: 69%

“…Numerous animal models have been created to tease apart the complex pathophysiology of ASD (Bey & Jiang, ; Hulbert & Jiang, ). One interesting finding from across various models is that housing rodents in an enriched environment, including more space and objects in which to interact and in some cases more rodents, prevents the expression of ASD‐like behavioral phenotypes (Favre et al, ; Garbugino, Centofante, & D'Amato, ; Kerr, Silva, Walz, & Young, ; Kondo et al, ; Lacaria, Spencer, Gu, Paylor, & Lupski, ; Lonetti et al, ; Nag et al, ; Oddi et al, ; Restivo et al, ; Reynolds, Urruela, & Devine, ; Schneider, Turczak, & Przewłocki, ; Yamaguchi et al, ). Although the type of enrichment and the developmental stages during exposure varied considerably, all these previous studies reported improvements on at least one behavioral outcome and seldom reported any adverse effects of enrichment.…”

Section: Introductionmentioning

confidence: 99%

Environmental enrichment has minimal effects on behavior in the Shank3 complete knockout model of autism spectrum disorder

2018

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IntroductionSeveral studies have supported the use of enriched environments to prevent the manifestation of ASD‐like phenotypes in laboratory rodents. While the translational value of such experiments is unknown, the findings have been relatively consistent across many different models.MethodsIn the current study, we tested the effects of early environmental enrichment on a mouse model of ASD with high construct validity, the Shank3 ∆e4–22 mice our laboratory previously generated and characterized.ResultsContrary to previous reports, we found no benefits of enriched rearing, including no change in repetitive self‐grooming or hole‐board exploration. Instead, we found that early environmental enrichment increased anxiety‐like behavior in all mice regardless of genotype and decreased motor performance specifically in wild‐type mice.ConclusionsAlthough using a different enrichment protocol may have rescued the phenotypes in our mouse model, these results suggest that a “one‐size fits all” approach may not be the best when it comes to behavioral intervention for ASD and underscores the need for effective pharmaceutical development in certain genetic syndromes with severe symptom presentation.

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“…In Wistar rats that were prenatally exposed to VPA, environmental enrichment (rearing in enriched cages) was reported to result in lower locomotor activity, less repetitive/stereotypic-like behavior, decreased anxiety-like behavior, increased number of social exploration and total social behaviors [59] . In ICR mice subjected to prenatal VPA exposure, environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment [60] . Prenatal VPA exposure also resulted in decreased dendritic spine density in the hippocampal CA1 region and this change could also be reversed by enriched housing [60] .…”

Section: Effect Of Environmental Enrichment On Chemical Induced Autismentioning

confidence: 95%

“…In ICR mice subjected to prenatal VPA exposure, environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment [60] . Prenatal VPA exposure also resulted in decreased dendritic spine density in the hippocampal CA1 region and this change could also be reversed by enriched housing [60] .…”

Section: Effect Of Environmental Enrichment On Chemical Induced Autismentioning

confidence: 95%

Environmental Enrichment Intervention in Animal Models of Autism

Xiao¹

2017

J Psychiatry Brain Sci.

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Autism spectrum disorder (ASD) is a complex neurodevelopment disorder caused by genetic and environmental factors. Animal models of autism could help to explore the cellular and molecular mechanisms underlying the pathogenesis and treatment approaches of this disease. Environmental enrichment has been demonstrated to exert beneficial effects in wild-type rodents as well as animal models of various neurological and psychiatric disorders. Here we review the findings about the effect of environmental enrichment on animal models of autism. Generally, environmental enrichment results in less anxietylike behavior, reduces repetitive behavior and the deficits in social and cognitive behaviors. Environmental enrichment therefore appears to be an effective model for non-pharmacological intervention in autism therapy.Autism spectrum disorder (ASD) is a complex neurodevelopment disorder, characterized by core features of impairments in social interaction and communication, and repetitive and stereotyped behaviors [1] , along with some co-occurring symptoms such as sleeping disorder, anxiety and aggression [2] . The exact etiology of autism remains unclear. Numerous studies on twins and siblings found a more than 90 % concordance rates in monozygotic twins [3,4] , as compared with 0 -10 % in dizygotic twins [3,4] and 3 -14 % in siblings [5][6][7] , which revealed the contribution of genetic factors to this disorder.

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Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice

Cited by 71 publications

References 44 publications

Motor Impairments Correlate with Social Deficits and Restricted Neuronal Loss in an Environmental Model of Autism

Motor Impairments Correlate with Social Deficits and Restricted Neuronal Loss in an Environmental Model of Autism

Environmental enrichment has minimal effects on behavior in the Shank3 complete knockout model of autism spectrum disorder

Environmental Enrichment Intervention in Animal Models of Autism

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