3-Nitropropionic acid induces behavioral alterations in adult zebrafish: Role of antioxidants on behavioral dysfunction.

Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive motor and non-motor symptoms, including neuropsychiatric disturbance and cognitive dysfunction. Pathogenic mechanisms of HD, leading to neuronal cell death, include neurodegeneration and oxidative stress. 3-Nitropropionic acid (3-NPA), a natural toxin that promotes the irreversible suppression of mitochondrial complex II, has been used to study HD pathogenesis in animal models. This neurotoxin mimics the biochemical, central neurodegeneration, peripheral, and behavioral phenotype alterations observed in HD. Here, we investigated the effects of 3-NPA (60 mg/kg) on oxidative stress parameters on brain tissue. We also evaluated the effects of three antioxidant compounds on 3-NPA-induced behavioral phenotypes in adult zebrafish. Adult zebrafish received a single acute intraperitoneal injection of vitamin C, creatine, or melatonin after chronic administration of 3-NPA (60 mg/kg) for 24 days. 3-NPA neither changed thiobarbituric acid reactive substances (TBARS) nor nonprotein thiol levels. However, vitamin C and creatine treatments recovered the hypolocomotion induced by 3-NPA. Additionally, vitamin C and melatonin treatments improved the memory dysfunction caused by 3-NPA. Altogether, our findings showed that vitamin C, creatine, and melatonin are beneficial in managing HD-like behavioral phenotypes. Thus, these antioxidants could be considered complementary pharmacotherapies for the treatment of late-stage HD symptoms.