Neuroprotective effects of Withania somnifera in BPA induced-cognitive dysfunction and oxidative stress in mice

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Behavioral and Brain Functions Open Access

RESEARCH

Neuroprotective effects of Withania somnifera in BPA induced‑cognitive dysfunction and oxidative stress in mice Hareram Birla†, Chetan Keswani†, Sachchida Nand Rai, Saumitra Sen Singh, Walia Zahra, Hagera Dilnashin, Aaina Singh Rathore and Surya Pratap Singh*

Abstract  Background:  Bisphenol A (BPA), a major endocrine disruptor and a xenobiotic compound is used abundantly in the production of polycarbonate plastics and epoxy resins. Human exposure to this compound is primarily via its leaching from the protective internal epoxy resin coatings of containers into the food and beverages. In addition, the plastics used in dental prostheses and sealants also contain considerable amount of BPA and have a high risk of human exposure. Since it is a well-known endocrine disruptor and closely mimics the molecular structure of human estrogen thereby impairing learning and memory. Withania somnifera (Ws), commonly known as Ashwagandha is known for its varied therapeutic uses in Ayurvedic system of medicine. The present study was undertaken to demonstrate the impairment induced by BPA on the spatial learning, working memory and its alleviation by Ws in Swiss albino mice. The study was conducted on thirty Swiss albino mice, randomly distributed among three groups: control, BPA and BPA + Ws. The behavioral recovery after treatment with Ws was investigated using the Y-maize and Morris water maize test. Whereas, for the estimation of recovery of NMDA receptor which is related to learning and memory in hippocampus region by western blot and immunohistochemistry. Furthermore, the oxidative stress and antioxidant level was assessed by biochemical tests like MDA, SOD and catalase. Results:  The study revealed that administration of Ws alleviated the behavioral deficits induced by BPA. Alongside, Ws treatment reinstated the number of NMDA receptors in hippocampus region and showed anti-oxidative property while ameliorating the endogenous anti-oxidant level in the brain. Conclusion:  These findings suggest that Ws significantly ameliorates the level of BPA intoxicated oxidative stress thereby potentially treating cognitive dysfunction which acts as the primary symptom in a number of neurodegenerative diseases. Keywords:  Cognitive impairment, Neurotoxicity, Oxidative stress, Spatial memory, Reactive oxygen species, Biomarkers Background Bisphenol A (BPA, 4zx, 40-isopropylidene-2-diphenol) is the building block in the manufacture of polycarbonate plastics, epoxy resins, compact discs, dental sealants and thermal papers [1]. The primary source of BPA exposure in human population, worldwide is due *Correspondence: [email protected] † Hareram Birla and Chetan Keswani contributed equally to this work Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India

to its ubiquitous presence in food and beverage packaging [2]. The different routes of BPA exposure are oral, transdermal and through inhalation [3]. Previous studies have reported the pr