Motor impairments correlate with social deficits and restricted neuronal loss in an environmental model of autism



Motor impairments are amongst the earliest and most consistent signs of autism spectrum disorders (ASD) but are not used as diagnostic criteria. In addition, the relationship between motor and cognitive impairments and their respective neural substrates remain unknown.


Here, we aimed at determining whether a well-acknowledged animal model of ASD, the valproic acid (VPA) model, displays motor impairments and whether they may correlate with social deficits and neuronal loss within motor brain areas. For this, pregnant female mice (C57BL/6J) received VPA (450 mg/kg) at E12.5 and offspring underwent a battery of behavioral analyses before being sacrificed for histological correlates in motor cortex, nigrostriatal pathway and cerebellum.


We show that while VPA male mice show both social and motor impairments, female mice only show motor impairments. Prenatal VPA exposure induces specific cell loss within the motor cortex and cerebellum and that is of higher magnitude in males than in females. Finally, we demonstrate that motor dysfunction correlates with reduced social behavior and that motor and social deficits both correlate with a loss of Purkinje cells within the Crus I cerebellar area.


Our results suggest that motor dysfunction could contribute to social and communication deficits in ASD and that motor and social deficits may share common neuronal substrates in the cerebellum. A systematic assessment of motor function in ASD may potentially help the quantitative diagnosis of ASD and strategies aimed at improving motor behavior may provide a global therapeutic benefit.


Keywords: valproic acid, cerebellum, motor cortex, gait, Purkinje cells