Abstract
Altered function or presence of inhibitory neurons is documented in autism spectrum disorders (ASD), but the mechanism underlying this alternation is poorly understood. One major subtype of inhibitory neurons altered is the parvalbumin (PV)-containing neurons with reduced density and intensity in ASD patients and model mice. A subpopulation of PV+ neurons expresses perineuronal nets (PNN). To better understand whether the relationship between PV and PNN is altered in ASD, we measured quantitatively the intensities of PV and PNN in single PV+ neurons in the prelimbic prefrontal cortex (PrL-PFC) of a valproic acid (VPA) model of ASD at different ages. We found a decreased PV intensity but increased PNN intensity in VPA mice. The relationship between PV and PNN intensities is altered in VPA mice, likely due to an “abnormal” subpopulation of neurons with an altered PV-PNN relationship. Furthermore, reducing PNN level using in vivo injection of chondroitinase ABC corrects the PV expression in adult VPA mice. We suggest that the interaction between PV and PNN is disrupted in PV+ neurons in VPA mice which may contribute to the pathology in ASD.
Highlights
Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disorders that share core clinical symptoms in social communication deficits and repetitive behaviors (Lord et al, 2018)
We have focused on quantitative changes in the PV and perineuronal nets (PNN) intensities and the relationship between them in the same neuron in a valproic acid (VPA) model of ASD
Our key finding is an altered relationship between PV and PNN levels, and the emergence of an abnormal subpopulation with an unbalanced PV-PNN relationship, in the PrL-prefrontal cortex (PFC) of VPA mice
Summary
Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disorders that share core clinical symptoms in social communication deficits and repetitive behaviors (Lord et al, 2018). The prevalence of the disease has been increasing, from 1% reported in 2012 to 1.5% in developed countries (Lyall et al, 2017). In-utero exposure of rodents to valproic acid (VPA) represents a robust model of autism exhibiting behavioral phenotypes in juvenile VPA rats and mice and persist into adulthood, all related to core human ASD symptoms (Ornoy et al, 2016). This model might better mimic idiopathic ASD. In the VPA rat model, a reduction in dendritic spine density in the prefrontal cortex (PFC) but an increase in spine number in the ventral hippocampus was reported (Bringas et al, 2013; Nicolini and Fahnestock, 2018)
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