Mechanisms of Valproic acid-Induced Autism: Canonical Wnt-β- Catenin Pathway

Document Type : Mini-reviews

Authors

1 Egypt Healthcare Authority, Comprehensive Health Insurance, Port-Said, Egypt

2 Pharmacology and Toxicology Department, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt.

3 Department of Pharmacology & Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt

4 Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt

Abstract

Abstract: 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 stube 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/β-Catenin pathways as possible mechanism involved in autism induction upon VPA use.

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