Effects of β-Glucans on Pro-Inflammatory Markers and Behavioral Phenotype in a Valproic Acid (VPA)-Induced Autism Model in Zebrafish
4 affiliations
- 1Neurobiology and Molecular Medicine Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- 2Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
- 3Department of Veterinary Sciences, University of Pisa, 56126 Pisa, Italy
- 4IRCCS Neuromed, 86077 Pozzilli, Italy
Abstract
Autism Spectrum Disorder (ASD) is a multifactorial neurodevelopmental condition in which neuroinflammation, oxidative stress, and synaptic dysfunction act as converging mechanisms. Prenatal exposure to valproic acid (VPA), an antiepileptic drug and histone deacetylase inhibitor, is a recognized environmental risk factor associated with ASD-like phenotypes. Zebrafish, with conserved neuroimmune pathways, rapid development, and quantifiable social behavior, represents a robust model for investigating ASD pathophysiology and testing therapeutic candidates. This study aimed to assess if a previously selected concentration of VPA is capable of inducing persistent alterations from early development through adulthood, and to assess the potential of β-glucans, natural polysaccharides with antioxidant and immunomodulatory properties, to mitigate VPA-induced alterations. A multimodal approach included morphological evaluation, mitochondrial respiration, quantitative PCR of inflammatory markers, and behavioral assays targeting locomotion, anxiety-like responses, and social preference. Low-dose VPA (25 μM) induced developmental and behavioral difficulties, accompanied by a transient reduction in mitochondrial respiratory capacity. β-glucan supplementation attenuated selected VPA-induced alterations, including inflammatory gene-expression changes in larvae and behavioral alterations in adulthood. Overall, these findings provide preclinical evidence that β-glucans can modulate selected VPA-induced inflammatory, molecular and behavioral alterations and support further investigation of their potential effects in neurodevelopmental models.
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BibTeX
@article{camussi2026effects,
title = {{Effects of β-Glucans on Pro-Inflammatory Markers and Behavioral Phenotype in a Valproic Acid (VPA)-Induced Autism Model in Zebrafish}},
author = {Diletta Camussi and Maria Marchese and Asahi Ogi and Baldassare Fronte and Ferdinando Nicoletti and Filippo Maria Santorelli and Serena Mero},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209243},
url = {https://www.mdpi.com/1422-0067/27/20/9243},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Effects of β-Glucans on Pro-Inflammatory Markers and Behavioral Phenotype in a Valproic Acid (VPA)-Induced Autism Model in Zebrafish
AU - Diletta Camussi
AU - Maria Marchese
AU - Asahi Ogi
AU - Baldassare Fronte
AU - Ferdinando Nicoletti
AU - Filippo Maria Santorelli
AU - Serena Mero
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209243
UR - https://www.mdpi.com/1422-0067/27/20/9243
AB - Autism Spectrum Disorder (ASD) is a multifactorial neurodevelopmental condition in which neuroinflammation, oxidative stress, and synaptic dysfunction act as converging mechanisms. Prenatal exposure to valproic acid (VPA), an antiepileptic drug and histone deacetylase inhibitor, is a recognized environmental risk factor associated with ASD-like phenotypes. Zebrafish, with conserved neuroimmune pathways, rapid development, and quantifiable social behavior, represents a robust model for investigating ASD pathophysiology and testing therapeutic candidates. This study aimed to assess if a previously selected concentration of VPA is capable of inducing persistent alterations from early development through adulthood, and to assess the potential of β-glucans, natural polysaccharides with antioxidant and immunomodulatory properties, to mitigate VPA-induced alterations. A multimodal approach included morphological evaluation, mitochondrial respiration, quantitative PCR of inflammatory markers, and behavioral assays targeting locomotion, anxiety-like responses, and social preference. Low-dose VPA (25 μM) induced developmental and behavioral difficulties, accompanied by a transient reduction in mitochondrial respiratory capacity. β-glucan supplementation attenuated selected VPA-induced alterations, including inflammatory gene-expression changes in larvae and behavioral alterations in adulthood. Overall, these findings provide preclinical evidence that β-glucans can modulate selected VPA-induced inflammatory, molecular and behavioral alterations and support further investigation of their potential effects in neurodevelopmental models.
SN - 1422-0067
ER -