Abstract
Understanding the effects of environmental stimulation in autism can improve therapeutic interventions against debilitating sensory overload, social withdrawal, fear and anxiety. Here, we evaluate the role of environmental predictability on behavior and protein expression, and inter-individual differences, in the valproic acid (VPA) model of autism. Male rats embryonically exposed (E11.5) either to VPA, a known autism risk factor in humans, or to saline, were housed from weaning into adulthood in a standard laboratory environment, an unpredictably enriched environment, or a predictably enriched environment. Animals were tested for sociability, nociception, stereotypy, fear conditioning and anxiety, and for tissue content of glutamate signaling proteins in the primary somatosensory cortex, hippocampus and amygdala, and of corticosterone in plasma, amygdala and hippocampus. Standard group analyses on separate measures were complemented with a composite emotionality score, using Cronbach's Alpha analysis, and with multivariate profiling of individual animals, using Hierarchical Cluster Analysis. We found that predictable environmental enrichment prevented the development of hyper-emotionality in the VPA-exposed group, while unpredictable enrichment did not. Individual variation in the severity of the autistic-like symptoms (fear, anxiety, social withdrawal and sensory abnormalities) correlated with neurochemical profiles, and predicted their responsiveness to predictability in the environment. In controls, the association between socio-affective behaviors, neurochemical profiles and environmental predictability was negligible. This study suggests that rearing in a predictable environment prevents the development of hyper-emotional features in animals exposed to an autism risk factor, and demonstrates that unpredictable environments can lead to negative outcomes, even in the presence of environmental enrichment.
Highlights
Autism is a pervasive neurodevelopmental disorder, diagnosed behaviorally upon early childhood presentation of social impairment, abnormal communication, and inflexible behaviors
This study demonstrates that predictable environmental enrichment prevents the development of autistic-like hyperemotional behaviors in rats exposed prenatally to valproic acid (VPA)
We report that inter-individual variability in cognitive, sensory and affective systems are associated with the enhanced sensitivity to environmental enrichment predictability in individuals exposed to an autism risk factor
Summary
Autism is a pervasive neurodevelopmental disorder, diagnosed behaviorally upon early childhood presentation of social impairment, abnormal communication, and inflexible behaviors. It has been proposed that the autism spectrum results from hyper-connected and hyper-plastic neural microcircuits very early in neural development, leading to amplified sensory processing, memory formation and hyper-emotionality These unusual features of the autistic brain would render the world overly intense, and potentially aversive (Markram et al, 2007; Markram and Markram, 2010). If this is true, exposure to unpredictable environments and over-stimulation could, accelerate the development of autistic symptoms. Studying these issues could provide valuable insights for early diagnosis and individualized therapy
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