Obesity aggravates neuroinflammatory and neurodegenerative effects of bisphenol A in female rats

Abstract

Bisphenol A (BPA), a common plasticizer, is categorized as a neurotoxic compound. Its impact on individuals exhibits sex-linked variations. Several biological and environmental factors impact the degree of toxicity. Moreover, nutritional factors have profound influence on toxicity outcome. BPA has been demonstrated to be an obesogen. However, research on the potential role of obesity as a confounding factor in BPA toxicity is lacking. We studied the neurodegenerative effects in high-fat diet (HFD)-induced obese female rats after exposure to BPA (10 mg/L via drinking water for 90 days). Four groups were taken in this study – Control, HFD, HFD + BPA and BPA. Cognitive function was evaluated through novel object recognition (NOR) test. Inflammatory changes in brain, and changes in hormonal level, lipid profile, glucose tolerance, oxidative stress, and antioxidants were also determined. HFD + BPA group rats showed a significant decline in memory function in NOR test. The cerebral cortex (CC) of the brain showed increased neurodegenerative changes as measured by microtubule-associated protein-2 (MAP-2) accompanied by histopathological confirmation. The increased level of neuroinflammation was demonstrated by microglial activation (Iba-1) and protein expression of nuclear factor– kappa B (NF-КB) in the brain. Obesity also caused significant (p < 0.05) increase in lipid peroxidation accompanied by reduced activities of antioxidant enzymes (glutathione S-transferase, catalase and glutathione peroxidase) and decrease in reduced-glutathione (p < 0.05) when compared to non-obese rats with BPA treatment. Overall, study revealed that obesity serves as a risk factor in the toxicity of BPA which may exacerbate the progression of neurological diseases.

Keywords:

• Endocrine disrupting chemicals
• metabolic disorders
• neurodegeneration
• neuroinflammation
• hormonal imbalance

Acknowledgements

We would like to acknowledge Department of Science and Technology (DST) and University Grant Commission (UGC) for sponsoring research related resources.

Credit authorship contributions

Anuradha Mangla – Conceptualization, data curation, formal analysis, investigation, methodology, writing- original draft; Poonam Goswami – Formal analysis and methodology; Bhaskar Sharma – Methodology and Visualization; Suramya Suramya – Investigation and methodology; Garima Jindal – Investigation and methodology; Mehjbeen Javed – Methodology and writing – reviews & editing; Mohd. Anas Saifi – Methodology; Suhel Parvez – Supervision and Validation; Tapas Chandra Nag – Methodology and visualization; Sheikh Raisuddin – Conceptualization, data curation, funding acquisition, investigation, project administration, resources, supervision, writing – original draft and writing – review & editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of Data and materials

Data will be available upon request to the corresponding author.

Additional information

Funding

This work was supported by the University Grant Commission (UGC) in the form of a Senior Research Fellowship to Ms. Anuradha Mangla (Grant Reference no. 190510116354) and the Indian Council of Medical Research (ICMR) (Project no. 5/4-5 Ad-hoc/Neuro/231/2020-NCD-1) for providing the research fund.