Neuro-regulator role of H2S in astrocyte activation and its effects on neurological damage and behavior of VPA-exposed rats
- 1Department of Children’s and Adolescent Health, Public Health College of Harbin Medical University
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder increasingly associated with aberrant astrocyte activation. Hydrogen sulfide (H2S) has recently emerged as a key regulator of astrocyte function, yet its role in ASD remains largely unexplored. Here, we investigated the association between H₂S modulation, ASD-like phenotypes, and astrocyte activation. In valproic acid (VPA)-exposed rats, H₂S were modulated using α-lipoic acid (LA) or aminooxyacetic acid (AOAA), a cystathionine β-synthase (CBS) inhibitor. Behavioral performance, neuronal injury, astrocyte phenotypes, H₂S levels, CBS expression and the homocysteine/cystathionine ratio were evaluated in vivo and in primary astrocytes. VPA-exposed rats exhibited reduced H₂S levels and CBS expression, an increased homocysteine/cystathionine ratio, ASD-like behavioral deficits and neuronal injury, and astrocyte activation toward a neurotoxic A1 phenotype. Elevation of H2S by LA was associated with improvements in ASD behavioral performance, reduced neuronal damage, reduced inflammatory cytokines and suppressed astrocyte activation, with changes in astrocyte marker expression towards a more A2-like, neuroprotective profile. Conversely, AOAA reversed these beneficial effects. Collectively, these findings suggested enhanced H₂S signaling is linked to improvements in ASD-like behavioral and neuropathological abnormalities, alongside modulation of astrocyte activation involving the CBS/H₂S pathway. These findings highlight the potential involvement of the CBS/H₂S axis in ASD-related pathology.
Related
- The carbohydrate utilization regulator Cbr1 coordinates nutrient-specific gene activation with selective carbon catabolite repression in a basidiomycete yeast
- MiR-208b-3p is an upstream regulator of redox-associated cardiomyocyte survival
- Taurine is a functional regulator of transthyretin; implication in transthyretin-induced hypothyroidism and amyloidosis
- Single-cell and intercellular communication analyses reveal DLL3 as a key regulator in the glioma tumor microenvironment
- If Becker Muscular Dystrophy Initially Manifests with Heart Disease and Rhabdomyolysis, Neurological Work-up Is Imperative
BibTeX
@article{wang2026neuroregulator,
title = {{Neuro-regulator role of H2S in astrocyte activation and its effects on neurological damage and behavior of VPA-exposed rats}},
author = {Haoran Wang and Lingyuan Yang and Jingyi Hu and Yi Jiang and Yuting Zhang and Junyu Ren and Lijie Wu and Mingyang Zou},
journal = {Communications Biology},
year = {2026},
month = jun,
doi = {10.1038/s42003-026-10510-7},
url = {https://doi.org/10.1038/s42003-026-10510-7},
note = {CC BY},
}
RIS
TY - JOUR
TI - Neuro-regulator role of H2S in astrocyte activation and its effects on neurological damage and behavior of VPA-exposed rats
AU - Haoran Wang
AU - Lingyuan Yang
AU - Jingyi Hu
AU - Yi Jiang
AU - Yuting Zhang
AU - Junyu Ren
AU - Lijie Wu
AU - Mingyang Zou
PY - 2026
DA - 2026/06/01
JO - Communications Biology
DO - 10.1038/s42003-026-10510-7
UR - https://doi.org/10.1038/s42003-026-10510-7
AB - Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder increasingly associated with aberrant astrocyte activation. Hydrogen sulfide (H2S) has recently emerged as a key regulator of astrocyte function, yet its role in ASD remains largely unexplored. Here, we investigated the association between H₂S modulation, ASD-like phenotypes, and astrocyte activation. In valproic acid (VPA)-exposed rats, H₂S were modulated using α-lipoic acid (LA) or aminooxyacetic acid (AOAA), a cystathionine β-synthase (CBS) inhibitor. Behavioral performance, neuronal injury, astrocyte phenotypes, H₂S levels, CBS expression and the homocysteine/cystathionine ratio were evaluated in vivo and in primary astrocytes. VPA-exposed rats exhibited reduced H₂S levels and CBS expression, an increased homocysteine/cystathionine ratio, ASD-like behavioral deficits and neuronal injury, and astrocyte activation toward a neurotoxic A1 phenotype. Elevation of H2S by LA was associated with improvements in ASD behavioral performance, reduced neuronal damage, reduced inflammatory cytokines and suppressed astrocyte activation, with changes in astrocyte marker expression towards a more A2-like, neuroprotective profile. Conversely, AOAA reversed these beneficial effects. Collectively, these findings suggested enhanced H₂S signaling is linked to improvements in ASD-like behavioral and neuropathological abnormalities, alongside modulation of astrocyte activation involving the CBS/H₂S pathway. These findings highlight the potential involvement of the CBS/H₂S axis in ASD-related pathology.
SN - 2399-3642
ER -