Flores-Prieto Bernardo, Caycho-Salazar Flower, Manzo Jorge, Hernández-Aguilar María Elena, Coria-Avila Alfonso Genaro, Herrera-Covarrubias Deissy, Rojas-Dúran Fausto, Aranda-Abreu Gonzalo Emiliano, Pérez-Estudillo Cesar Antonio, Toledo-Cárdenas María Rebeca
Doctorate in Brain Research, Universidad Veracruzana, Veracruz 91190, Mexico;
Institute of Brain Research, Universidad Veracruzana, Veracruz 91190, Mexico.
NeuroSci. 2024 Apr 22;5(2):128-140. doi: 10.3390/neurosci5020009. eCollection 2024 Jun.
The etiology of autism spectrum disorder (ASD) has been linked to both genetic and epigenetic factors. Among the epigenetic factors, exposure to valproic acid (VPA), an antiepileptic and mood-modulating drug, has been shown to induce characteristic traits of ASD when exposed to during embryogenesis. Conversely, in animal models, enriched environment (EE) has demonstrated positive behavioral and neural effects, suggesting its potential as a complementary treatment to pharmacological approaches in central nervous system disorders. In this study, we utilized zebrafish to model ASD characteristics induced by VPA and hypothesized that sensory stimulation through EE could ameliorate the behavioral and neuroanatomical features associated with ASD. To test this hypothesis, we assessed social behavior, cerebellar volume, and Purkinje cell populations via histology and immunohistochemistry after exposing the fish to EE. The results revealed that zebrafish exposed to VPA exhibited social deficits, reduced cerebellar cortex volume, and a decrease in c-Fos-positive cells in the Purkinje layer. In contrast, VPA-exposed fish treated with EE showed increased socialization, augmented cerebellar cortex volume, and an elevation in c-Fos-positive Purkinje cells. These findings suggest that alterations induced by VPA may be ameliorated through EE treatment, highlighting the potential therapeutic impact of sensory stimulation in conditions related to ASD.
自闭症谱系障碍（ASD）的病因与遗传和表观遗传因素均有关联。在表观遗传因素中，接触丙戊酸（VPA），一种抗癫痫和调节情绪的药物，已被证明在胚胎发育期间接触时会诱发ASD的特征性 traits。相反，在动物模型中，丰富环境（EE）已显示出积极的行为和神经效应，表明其作为中枢神经系统疾病药物治疗方法的补充治疗的潜力。在本研究中，我们利用斑马鱼对由VPA诱导的ASD特征进行建模，并假设通过EE进行感觉刺激可以改善与ASD相关的行为和神经解剖学特征。为了验证这一假设，我们在将鱼暴露于EE后，通过组织学和免疫组织化学评估了社交行为、小脑体积和浦肯野细胞群体。结果显示，暴露于VPA的斑马鱼表现出社交缺陷、小脑皮质体积减小以及浦肯野层中c-Fos阳性细胞减少。相比之下，用EE处理的暴露于VPA的鱼表现出社交增加、小脑皮质体积增大以及浦肯野细胞中c-Fos阳性细胞增加。这些发现表明，VPA诱导的改变可能通过EE治疗得到改善，突出了感觉刺激在与ASD相关病症中的潜在治疗作用。
