Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-CAS, Panjab University, Chandigarh-160014, India.
TR(i)P for Health Laboratory, Centre of Excellence in Functional Foods, National Agri-Food Biotechnology Institute (NABI), Knowledge City-Sector 81, Sahibzada Ajit Singh Nagar (SAS Nagar), Punjab, India.
Eur J Pharmacol. 2024 Nov 5;982:176902. doi: 10.1016/j.ejphar.2024.176902. Epub 2024 Aug 15.
The 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.
In 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.
Niclosamide therapy significantly restored behavioral, biochemical, neurological, and molecular impairments. Hence, niclosamide could be a potential neurotherapeutic candidate for further studies for use in ASD.
本研究旨在探讨氯硝柳胺在自闭症谱系障碍（ASD）动物模型中的神经保护潜力，并进一步探讨 ERK/MAPK 信号通路如何促成这种作用。
为了在大鼠中产生类似自闭症的表型，将 1 M PPA 以 4 μl 的剂量经脑室注射。从第 3 天到第 30 天，给予氯硝柳胺（50 和 100mg/kg）和利培酮（1mg/kg）（用作标准）进行口服治疗。在第 14 天至第 28 天进行社交、刻板、焦虑、抑郁、新奇偏好、重复行为和坚持行为的行为评估。第 29 天处死动物，评估脑匀浆中的氧化应激标志物。使用 ELISA 试剂盒测定神经炎症细胞因子如 TNF-α、IL-6、NF-κB、IFN-γ 和谷氨酸的水平。为了评估 ERK/MAPK 信号通路的参与情况，还测量了 Nrf2 和 ERK2 的水平。
氯硝柳胺治疗显著恢复了行为、生化、神经和分子损伤。因此，氯硝柳胺可能是进一步研究用于 ASD 的潜在神经治疗候选药物。
