Scholarlink

<p>Autism Spectrum Disorder (ASD) is associated with neuroinflammation and oxidative stress that disrupt neurodevelopmental processes. Resveratrol (RSV) is a polyphenol with antioxidant and anti-inflammatory properties, but its poor bioavailability limits therapeutic use. This study investigated whether PEGylated liposomes encapsulating RSV (LipRSV) could modulate oxidative and behavioral alterations in a valproic acid (VPA)-induced rat model of ASD.&#xa0;PEGylated LipRSV were synthesized, characterized as hemocompatible, and administered to offspring from postnatal day (PND) 6 to 27. Behavioral tests included developmental milestones, olfactory discrimination, negative geotaxis, open field, and three-chamber social interaction. Oxidative stress markers and neurotrophins (BDNF, NGF) were quantified in the following brain regions: hippocampus, hypothalamus, striatum, cerebellum, frontal and posterior cortex.&#xa0;LipRSV exerted limited and region-dependent redox effects, reducing ROS levels only in the hippocampus, cerebellum, and posterior cortex, while failing to improve behavioral outcomes and being associated with unfavorable neurochemical alterations, including reduced BDNF and NGF levels. Importantly, LipRSV also induced behavioral deficits, redox imbalance, and neurochemical alterations in control animals, indicating treatment-related effects in the absence of VPA exposure.&#xa0;LipRSV modulated oxidative stress in a region-dependent manner without improving behavioral deficits in the VPA model and was associated with reduced BDNF and NGF levels. This study provides evidence that modulation of oxidative stress alone is insufficient to rescue behavioral phenotypes in the VPA model of ASD. These findings highlight the partial neurochemical efficacy and translational limitations of this formulation, suggesting the need for optimized nanocarrier design and dosing strategies in ASD pharmacotherapy.</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

PEGylated Liposomal Resveratrol Induces Region-Specific Redox Modulation Without Behavioral or Neurotrophin Recovery in a VPA Model of Autism

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月1日

查看全文
  • Victória Linden de Rezende,
  • Maria Fernanda Pedro Ebs,
  • Flávia da Silva Daros,
  • Maiara de Aguiar da Costa,
  • Sofia Januário Bolan,
  • Germano Lapa Viana,
  • Leonardo Pelegrini,
  • Nathan de Souza Colonetti,
  • Maria Júlia Ferro Spillere,
  • Giseli da Silva Souza,
  • Rafaela de Sousa Anastácio,
  • Ellen De-Pieri,
  • Júlio César Claudino dos Santos,
  • Ricardo Andrez Machado de Ávila,
  • Alexandre Gonçalves Dal-Bó,
  • Cinara Ludvig Gonçalves

摘要

Autism Spectrum Disorder (ASD) is associated with neuroinflammation and oxidative stress that disrupt neurodevelopmental processes. Resveratrol (RSV) is a polyphenol with antioxidant and anti-inflammatory properties, but its poor bioavailability limits therapeutic use. This study investigated whether PEGylated liposomes encapsulating RSV (LipRSV) could modulate oxidative and behavioral alterations in a valproic acid (VPA)-induced rat model of ASD. PEGylated LipRSV were synthesized, characterized as hemocompatible, and administered to offspring from postnatal day (PND) 6 to 27. Behavioral tests included developmental milestones, olfactory discrimination, negative geotaxis, open field, and three-chamber social interaction. Oxidative stress markers and neurotrophins (BDNF, NGF) were quantified in the following brain regions: hippocampus, hypothalamus, striatum, cerebellum, frontal and posterior cortex. LipRSV exerted limited and region-dependent redox effects, reducing ROS levels only in the hippocampus, cerebellum, and posterior cortex, while failing to improve behavioral outcomes and being associated with unfavorable neurochemical alterations, including reduced BDNF and NGF levels. Importantly, LipRSV also induced behavioral deficits, redox imbalance, and neurochemical alterations in control animals, indicating treatment-related effects in the absence of VPA exposure. LipRSV modulated oxidative stress in a region-dependent manner without improving behavioral deficits in the VPA model and was associated with reduced BDNF and NGF levels. This study provides evidence that modulation of oxidative stress alone is insufficient to rescue behavioral phenotypes in the VPA model of ASD. These findings highlight the partial neurochemical efficacy and translational limitations of this formulation, suggesting the need for optimized nanocarrier design and dosing strategies in ASD pharmacotherapy.