Brainstem motor neuron dysmorphology and excitatory/inhibitory imbalance in an animal model of autism.

BACKGROUND

Autism spectrum disorder (ASD) is a developmental disorder associated with in utero exposure to the antiepileptic valproic acid (VPA) in humans, and similar exposure serves as a validated animal model. Animals exposed to VPA in utero have a number of structural, function and behavioural deficits associated with ASD. Furthermore, VPA-exposed animals have shorter body lengths, lower body and brain weights. This difference in body weight may result from impaired caloric intake due to impaired oropharyngeal function.

MATERIALS AND METHODS

Specifically, it is hypothesized that in utero VPA exposure results in fewer lower motor neurons associated with feeding behaviours, that surviving neurons will exhibit dysmorphology and altered balance of excitatory and inhibitory inputs. Further, it is hypothesized that VPA exposure will result in altered oropharyngeal musculature that will impact skull morphology.

RESULTS

These hypotheses were investigated using quantitative morphometrics and immunofluorescence.

CONCLUSIONS

Results support dysmorphology and excitatory/inhibitory imbalance and these alterations may contribute to dysphagia and poor weight gain in VPA-exposed animals.