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

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Behavioral Neuroscience

Background:

• Prenatal exposure to valproic acid (VPA) induces autism spectrum disorder (ASD)-like phenotypes in mice, including behavioral and cognitive deficits.
• Environmental enrichment (EE) has shown potential in ameliorating some ASD-related behaviors in rodent models, but its impact on cognitive impairment remains less understood.

Purpose of the Study:

• To investigate the effects of early environmental enrichment on behavioral abnormalities and hippocampal neuromorphological changes in mice prenatally exposed to VPA.
• To explore the role of dendritic spine formation and synaptic protein expression in the hippocampus following EE in VPA-exposed mice.

Main Methods:

• Mice were exposed to VPA prenatally and then housed in either standard or enriched environments for 4 weeks starting at 4 weeks of age.
• Behavioral tests assessed locomotion, anxiety, social interaction, and cognition.
• Hippocampal tissue was analyzed for brain-derived neurotrophic factor (BDNF) mRNA, postsynaptic density protein-95 (PSD-95) mRNA, and SHANK2 mRNA levels, along with dendritic spine density.

Main Results:

• Environmental enrichment increased hippocampal BDNF mRNA levels in both control and VPA-exposed mice.
• In VPA-exposed mice, EE significantly improved anxiety-like behavior, social deficits, and cognitive impairment, but not hypolocomotion.
• Prenatal VPA exposure led to reduced dendritic spine density and decreased PSD-95 and SHANK2 mRNA in the hippocampus, all of which were ameliorated by EE.

Conclusions:

• Early environmental enrichment effectively improves a range of ASD-like behaviors, including cognitive deficits, in mice exposed to VPA prenatally.
• EE enhances hippocampal synaptic plasticity, evidenced by improved dendritic spine density and synaptic protein expression.
• These findings highlight EE as a potential therapeutic strategy for mitigating ASD-like phenotypes by targeting synaptic function.