Animal model of autism induced by prenatal exposure to valproic acid: translational validity
Autism is a neurodevelopmental disorder characterised behaviourally by impairments in social interaction, verbal and nonverbal communication, and by restricted, repetitive patterns of behaviour, interests, and activities. I will present one of the best characterized animal models of autism induced by prenatal exposure to valproic acid (VPA). Rodents exposed to VPA on the 12th day of gestation show several brain abnormalities, resembling those found at autopsy and imaging studies of autistic patients as well as long-term behavioural deficits including decreased sociability, hyperactivity, stereotypic activity, increased anxiety, lower sensitivity to pain, and diminished acoustic prepulse inhibition; and several molecular and immunological aberrations, e.g., altered functioning of opioidergic, serotonergic, dopaminergic, and glutamatergic systems, and decreased cellular immunity. Observed aberrations are more prominent in males and can be reversed by environmental enrichment. Similarities in behavioural, anatomical, biochemical and immunological pathology in autism and VPA rodents suggest the utility of this model for defining common pathways for dysregulation of normal developmental patterns and assessing the time course and sources of vulnerability to autism. I will show recent empirical and theoretical applications of VPA model towards better understanding and potential new treatments for autism.