Repurposing of niclosamide, an anthelmintic, by targeting ERK/MAPK signaling pathway in the experimental paradigm of autism spectrum disorders

Abstract

AimThe current study explores niclosamide's neuroprotective potential in an animal model of autism spectrum disorder (ASD) and goes further to understand how the ERK/MAPK signaling pathway is thought to contribute to this activity. MethodsIn order to create an autism-like phenotype in rats, 4 μl of 1 M PPA was infused intracerebroventricularly. The oral treatment with niclosamide (50 and 100 mg/kg) and risperidone (1 mg/kg) (used as standard) was given from 3rd to 30th day. Between the 14th and 28th day, behavioral assessments were made for sociability, stereotypy, anxiety, depression, novelty preference, repetitive behavior, and perseverative behavior. The animals were euthanized on the 29th day, and oxidative stress markers were assessed in the brain homogenate. The levels of neuroinflammatory cytokines such as TNF-α, IL-6, NF-κB, IFN-γ and glutamate were estimated using ELISA kits. To assess the involvement of the ERK/MAPK signaling pathway, levels of Nrf2 and ERK2 were also measured. Key findingsNiclosamide therapy significantly restored behavioral, biochemical, neurological, and molecular impairments. Hence, niclosamide could be a potential neurotherapeutic candidate for further studies for use in ASD.