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Behav Brain Res. 2017 Aug 30;333:67-73. doi: 10.1016/j.bbr.2017.06.035. Epub 2017 Jun 24.

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

Author information

1
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
2
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
3
Department of Pharmacology, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan.
4
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan; Department of Pharmacology, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan.
5
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Suita, Osaka 565-0871, Japan; Division of Bioscience, Institute for Datability Science, Osaka University, Suita, Osaka 565-0871, Japan.
6
Department of Pharmacology, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Suita, Osaka 565-0871, Japan. Electronic address: takuma@dent.osaka-u.ac.jp.

Abstract

We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function.

KEYWORDS:

Autism; Behavioral abnormalities; Dendritic spines; Environmental enrichment; Valproic acid

PMID:
28655565
DOI:
10.1016/j.bbr.2017.06.035
[Indexed for MEDLINE]

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