Scholarlink

<p>Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder increasingly associated with aberrant astrocyte activation. Hydrogen sulfide (H<sub>2</sub>S) 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 H<sub>2</sub>S 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Neuro-regulator role of H2S in astrocyte activation and its effects on neurological damage and behavior of VPA-exposed rats

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月30日

查看全文
  • Haoran Wang,
  • Lingyuan Yang,
  • Jingyi Hu,
  • Yi Jiang,
  • Yuting Zhang,
  • Junyu Ren,
  • Lijie Wu,
  • Mingyang Zou

摘要

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.