TY - JOUR

T1 - Valproate Exposure as an In vitro Model for Studying Morpho-Molecular Features of ASD

T2 - A Systematic Review

AU - Vasconcelos, Quezia Damaris Jones Severino

AU - Serafini, Michele Aramburu

AU - Carletti, Jaqueline Vieira

AU - Aragão, Gislei Frota

AU - Gottfried, Carmem

AU - Bambini-Junior, Victorio

PY - 2025/4/28

Y1 - 2025/4/28

N2 - Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic and environmental basis. It frequently causes social and communication deficits, as well as repetitive behaviours. Valproic acid (VPA) has been shown to induce autisticlike features in animal models when administered during critical development periods. However, not much is known about its effect on cells to replicate ASD characteristics in vitro. Objective: This review explores in vitro VPA models to elucidate the molecular and morphological characteristics of ASD, emphasizing their potential and proposing directions for future research. Methods: PubMed, SciELO, Embase, Web of Science, and Scopus databases were searched, and 11 studies were included after screening. Results: The studies explored VPA's effects on various cell cultures, including human neural cell lines, primary adult neurons, and primary embryonic neurons. VPA was found to be neurotoxic in a dose- and time-dependent manner, with greater toxicity in immature and undifferentiated cells. In vitro, VPA can influence gene expression, increase oxidative stress, disrupt neurogenesis and synaptogenesis, affect the GABAergic system, and alter critical signaling pathways for brain development and cell differentiation, such as Wnt/β-catenin. Conclusion: In vitro models provide valuable insights into the morpho-molecular alterations induced by VPA and their connection to ASD. These findings highlight the need for further research into VPA's cellular effects to deepen our understanding of its role in ASD pathology.

AB - Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic and environmental basis. It frequently causes social and communication deficits, as well as repetitive behaviours. Valproic acid (VPA) has been shown to induce autisticlike features in animal models when administered during critical development periods. However, not much is known about its effect on cells to replicate ASD characteristics in vitro. Objective: This review explores in vitro VPA models to elucidate the molecular and morphological characteristics of ASD, emphasizing their potential and proposing directions for future research. Methods: PubMed, SciELO, Embase, Web of Science, and Scopus databases were searched, and 11 studies were included after screening. Results: The studies explored VPA's effects on various cell cultures, including human neural cell lines, primary adult neurons, and primary embryonic neurons. VPA was found to be neurotoxic in a dose- and time-dependent manner, with greater toxicity in immature and undifferentiated cells. In vitro, VPA can influence gene expression, increase oxidative stress, disrupt neurogenesis and synaptogenesis, affect the GABAergic system, and alter critical signaling pathways for brain development and cell differentiation, such as Wnt/β-catenin. Conclusion: In vitro models provide valuable insights into the morpho-molecular alterations induced by VPA and their connection to ASD. These findings highlight the need for further research into VPA's cellular effects to deepen our understanding of its role in ASD pathology.

U2 - 10.2174/0118715273374315250417094713

DO - 10.2174/0118715273374315250417094713

M3 - Journal article

VL - 24

JO - CNS & neurological disorders drug targets

JF - CNS & neurological disorders drug targets

SN - 1871-5273

ER -