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Article

Environmental Enrichment Rescues Social Behavioral Deficits and Synaptic Abnormalities in Pten Haploinsufficient Mice

Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA
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Academic Editors: Andreas G. Chiocchetti and Marc Woodbury-Smith
Genes 2021, 12(9), 1366; https://doi.org/10.3390/genes12091366
Received: 29 April 2021 / Revised: 20 August 2021 / Accepted: 26 August 2021 / Published: 30 August 2021
(This article belongs to the Special Issue Genetic and Phenotypic Subtypes of Autism Spectrum Disorder)
Pten germline haploinsufficient (Pten+/−) mice, which model macrocephaly/autism syndrome, show social and repetitive behavior deficits, early brain overgrowth, and cortical–subcortical hyperconnectivity. Previous work indicated that altered neuronal connectivity may be a substrate for behavioral deficits. We hypothesized that exposing Pten+/− mice to environmental enrichment after brain overgrowth has occurred may facilitate adaptation to abnormal “hard-wired” connectivity through enhancing synaptic plasticity. Thus, we reared Pten+/− mice and their wild-type littermates from weaning under either standard (4–5 mice per standard-sized cage, containing only bedding and nestlet) or enriched (9–10 mice per large-sized cage, containing objects for exploration and a running wheel, plus bedding and nestlet) conditions. Adult mice were tested on social and non-social assays in which Pten+/− mice display deficits. Environmental enrichment rescued sex-specific deficits in social behavior in Pten+/− mice and partially rescued increased repetitive behavior in Pten+/− males. We found that Pten+/− mice show increased excitatory and decreased inhibitory pre-synaptic proteins; this phenotype was also rescued by environmental enrichment. Together, our results indicate that environmental enrichment can rescue social behavioral deficits in Pten+/− mice, possibly through normalizing the excitatory synaptic protein abundance. View Full-Text
Keywords: environmental enrichment; synaptic plasticity; Pten; autism; neurodevelopment environmental enrichment; synaptic plasticity; Pten; autism; neurodevelopment
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MDPI and ACS Style

Clipperton-Allen, A.E.; Zhang, A.; Cohen, O.S.; Page, D.T. Environmental Enrichment Rescues Social Behavioral Deficits and Synaptic Abnormalities in Pten Haploinsufficient Mice. Genes 2021, 12, 1366. https://doi.org/10.3390/genes12091366

AMA Style

Clipperton-Allen AE, Zhang A, Cohen OS, Page DT. Environmental Enrichment Rescues Social Behavioral Deficits and Synaptic Abnormalities in Pten Haploinsufficient Mice. Genes. 2021; 12(9):1366. https://doi.org/10.3390/genes12091366

Chicago/Turabian Style

Clipperton-Allen, Amy E., Angela Zhang, Ori S. Cohen, and Damon T. Page 2021. "Environmental Enrichment Rescues Social Behavioral Deficits and Synaptic Abnormalities in Pten Haploinsufficient Mice" Genes 12, no. 9: 1366. https://doi.org/10.3390/genes12091366

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