RECORDS OF PHARMACEUTICAL AND BIOMEDICAL SCIENCES Mechanism of Valproic acid Induced Autism: Canonical Wnt-β-Catenin Pathway

Valproic acid (VPA) is anti-epileptic and mood stabilizer drug that induces autism spectrum disease (ASD). However, VPA has several side effects; hepatic steatosis, hepatotoxicity, hemorrhagic pancreatitis, encephalopathy, bone marrow suppression and metabolic disorders such as obesity. VPA proved to be unavoidable and could not be excluded in epileptic pregnant women. Non-controlled epileptic attacks during pregnancy produce high risk of injury to both mother and fetus. However, VPA crosses the placenta and accumulate in the fetal circulation with higher concentration than that in the maternal blood, causing toxicity and teratogenicity. Gestational VPA treatment for a life-threatening epilepsy caused numerous defects in children, including neural tube defects, intellectual impairments and cognitive-behavioral impairments. 8.9% of children exposed to VPA in utero develop autistic features. VPA exposure in the first trimester of gestation represented the highest risk for the child to develop autism, showed classical signs of autism, and developmental and behavioral delays. The full mechanisms of VPA are not fully elicited. This review discusses canonical Wnt

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