3-Nitropropionic acid induces histological and behavioral alterations in adult zebrafish: role of antioxidants on behavioral dysfunction

Huntingtons disease (HD) is a neurodegenerative disease marked by progressive motor and non-motor symptoms such as neuropsychiatric disruption and cognitive dysfunction. It has been reported that some pathogenic mechanisms resulting in neuronal cell death in this disease involve 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 understand the HD pathogenesis. This neurotoxin mimics the biochemical, central neurodegeneration, peripheral and behavioral phenotype alterations observed in HD. Here we investigated 3-NPA (60 mg/kg) effects on histological and oxidative stress parameters on brain and muscular tissues. We also evaluated the effects of three antioxidant compounds on 3-NPA-induced behavioral phenotypes in adult zebrafish. For the evaluation of the antioxidant effects, adult zebrafish were submitted to a single acute intraperitoneal injection of vitamin C, creatine, or melatonin following 3-NPA chronic administration (60 mg/kg). 3-NPA treatment caused neurodegeneration, but did not alter the muscular tissue. 3-NPA neither change thiobarbituric acid reactive substances (TBARS) nor nonprotein thiol levels. Vitamin C and creatine treatments recovered the hypolocomotion induced by 3-NPA. Also, vitamin C and melatonin treatments improved the memory dysfunction caused by 3-NPA. Altogether, our findings showed that the 3-NPA induces neurodegeneration in adult zebrafish, and the vitamin C, creatine, and melatonin are beneficial in managing HD-like behavioral phenotypes. Thus, these antioxidants could be thought as complementary pharmacotherapies for the treatment of late-stage HD symptoms.