PUBLICATION

Therapeutic effects of nanosilibinin in valproic acid-zebrafish model of autism spectrum disorder: Focusing on Wnt signaling pathway and autism spectrum disorder-related cytokines

Authors
Karimi, Z., Zarifkar, A., Mirzaei, E., Dianatpour, M., Dara, M., Aligholi, H.
ID
ZDB-PUB-240704-12
Date
2024
Source
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience   84(5): 454-468 (Journal)
Registered Authors
Keywords
Wnt signaling pathway, autism spectrum disorder, cytokine, silibinin, valproic acid, zebrafish
MeSH Terms
  • Valproic Acid*/pharmacology
  • Cytokines*/metabolism
  • Disease Models, Animal*
  • Zebrafish*
  • Autism Spectrum Disorder*/drug therapy
  • Wnt Signaling Pathway*/drug effects
  • Animals
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian/drug effects
(all 9)
PubMed
38961588 Full text @ Int. J. Dev. Neurosci.
Abstract
In this study, we delved into the intricate world of autism spectrum disorder (ASD) and its connection to the disturbance in the Wnt signaling pathway and immunological abnormalities. Our aim was to evaluate the impact of silibinin, a remarkable modulator of both the Wnt signaling pathway and the immune system, on the neurobehavioral and molecular patterns observed in a zebrafish model of ASD induced by valproic acid (VPA). Because silibinin is a hydrophobic molecule and highly insoluble in water, it was used in the form of silibinin nanoparticles (nanosilibinin, NS). After assessing survival, hatching rate, and morphology of zebrafish larvae exposed to different concentrations of NS, the appropriate concentrations were chosen. Then, zebrafish embryos were exposed to VPA (1 μM) and NS (100 and 200 μM) at the same time for 120 h. Next, anxiety and inattentive behaviors and the expression of CHD8, CTNNB, GSK3beta, LRP6, TNFalpha, IL1beta, and BDNF genes were assessed 7 days post fertilization. The results indicated that higher concentrations of NS had adverse effects on survival, hatching, and morphological development. The concentrations of 100 and 200 μM of NS could ameliorate the anxiety-like behavior and learning deficit and decrease ASD-related cytokines (IL1beta and TNFalpha) in VPA-treated larvae. In addition, only 100 μM of NS prevented raising the gene expression of Wnt signaling-related factors (CHD8, CTNNB, GSK3beta, and LRP6). In conclusion, NS treatment for the first 120 h showed therapeutic effect on an autism-like phenotype probably via reducing the expression of pro-inflammatory cytokines genes and changing the expression of Wnt signaling components genes.
Genes / Markers
Figures
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Fish
No data available
Antibodies
Orthology
Engineered Foreign Genes
No data available
Mapping
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Citation
Karimi, Z., Zarifkar, A., Mirzaei, E., Dianatpour, M., Dara, M., Aligholi, H. (2024) Therapeutic effects of nanosilibinin in valproic acid-zebrafish model of autism spectrum disorder: Focusing on Wnt signaling pathway and autism spectrum disorder-related cytokines. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 84(5):454-468.