PUBLICATION
Micromolar Valproic Acid Doses Preserve Survival and Induce Molecular Alterations in Neurodevelopmental Genes in Two Strains of Zebrafish Larvae
- Authors
- Messina, A., Boiti, A., Sovrano, V.A., Sgadò, P.
- ID
- ZDB-PUB-201002-198
- Date
- 2020
- Source
- Biomolecules 10(10): (Journal)
- Registered Authors
- Keywords
- AB inbred zebrafish strain, TU inbred zebrafish strain, VPA, ascl1a/b, dopamine, serotonin
- MeSH Terms
-
- Animals
- Anticonvulsants/adverse effects
- Anticonvulsants/pharmacology
- Anxiety/chemically induced
- Anxiety/drug therapy*
- Anxiety/genetics
- Anxiety/pathology
- Autism Spectrum Disorder/chemically induced
- Autism Spectrum Disorder/drug therapy*
- Autism Spectrum Disorder/genetics
- Autism Spectrum Disorder/pathology
- Disease Models, Animal
- Female
- Larva/drug effects
- Larva/genetics
- Metabolic Networks and Pathways/drug effects
- Metabolic Networks and Pathways/genetics
- Valproic Acid/adverse effects*
- Valproic Acid/pharmacology
- Valproic Acid/toxicity
- Zebrafish/genetics*
- Zebrafish/growth & development
- PubMed
- 32987891 Full text @ Biomolecules
Citation
Messina, A., Boiti, A., Sovrano, V.A., Sgadò, P. (2020) Micromolar Valproic Acid Doses Preserve Survival and Induce Molecular Alterations in Neurodevelopmental Genes in Two Strains of Zebrafish Larvae. Biomolecules. 10(10):.
Abstract
Autism spectrum disorders (ASDs) comprise a genetically heterogeneous group of conditions characterized by a multifaceted range of impairments and multifactorial etiology. Epidemiological studies have identified valproic acid (VPA), an anticonvulsant used to treat epilepsy, as an environmental factor for ASDs. Based on these observations, studies using embryonic exposure to VPA have been conducted in many vertebrate species to model ASD. The zebrafish is emerging as a popular model in biomedical research to study the molecular pathways involved in nervous system disorders. VPA exposure in zebrafish larvae has been shown to produce a plethora of effects on social, motor and anxiety behavior, and several genetic pathways altered by VPA have been described. However, the doses and regimen of administration reported in the literature are very heterogenous, creating contradictory results and posing serious limits to the interpretation of VPA action on neurodevelopment. To shed light on the toxic effect of VPA, we tested micromolar concentrations of VPA, using exposure for 24 and 48 h in two different zebrafish strains. Our results show that micromolar doses of VPA mildly affect embryo survival but are sufficient to induce molecular alterations in neurodevelopmental genes previously shown to be influenced by VPA, with substantial differences between strains.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping