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A recent study has shown maternal BPA consumption, a product commonly found in households, is associated with altered gene and protein expression previously connected to Alzheimer’s disease (AD).
BPA, short for bisphenol A, is a chemical that’s been used since the 1960’s to produce plastic. It’s nearly everywhere: when one heats a plastic bowl in the microwave, she exposes herself to relatively high levels of BPA (Mayo Clinic 2019) The FDA has observed potential negative health effects and, based on over 100 studies, established a No-Observed-Adverse-Effect-Level (NOAEL). A NOAEL is the highest dose of a chemical from which researchers found no negative effects on the consumer (U.S. National Library of Medicine). In, “Prenatal exposure to bisphenol A alters the transcriptome-interactome profiles of genes associated with Alzheimer’s disease in the offspring hippocampus,” researchers sought to investigate pathways disrupted by NOAEL BPA-exposure and found potential similarities to the dysfunction caused by Alzheimer’s disease.
The scientists began their study by performing an RNA-seq analysis, allowing them to see which sections of DNA have been transcribed to RNA for potential protein synthesis and to what degree. They gathered this data from six rat liters, evenly split between a control group and a BPA exposed group. Immediately, they found a significant number of genes expressed differently in BPA exposed rats versus control rats. To apply these findings to AD, the researchers identified the 109 genes most often shown to be dysregulated in Alzheimer’s. When comparing the genes abnormally expressed in AD to the genes abnormally expressed in BPA exposed fetuses, researchers found significant overlapping in the hippocampus.
Moving forward, researchers hoped to increase understanding of these specific associations. They used Ingenuity Pathway Analysis (IPA), which takes the unique expression of genes in BPA exposed rats and links them to potential biological pathways or know diseases. This allowed researchers to develop a map of the proteins and pathways effected by BPA exposure. Researchers found that the differentially expressed genes were highly associated with many neurological processes but the most interesting finding was a strong association with “NF-κB activation.” NF-Κb proteins are currently considered important neuroinflammatory proteins linked with Alzheimer’s.
Given this NF-κB link, researchers used immunostaining to assess the relationship between NF-κB protein expression and BPA exposed mice. They found a significant increase in the NF- κB transcription factors in the BPA exposed mice versus the controls. Interestingly, however, this was only increased in males, showing gender specific effects that are left to be further investigated.
In addition, researchers also assessed Bace1 gene expression in the rats because Bace1 expression has been suggested to be controlled by NF- κB transcription factors. It was then no surprise that in the BPA rats, the researchers found an increase in Base1 expression (also in a sex dependent manner). It’s important to note that Bace1 functions as an enzyme responsible for the breakdown of the APP protein, which in turn causes the clustering of a A β polypeptides. This process is one of the hallmarks of AD.
With this said, the researchers next investigated APP and A β expression. They were unable to find a significant relationship between BPA consumption (increased Base1 and NF- κB expression) and elevated APP or A β levels. Though they did see a nonsignificant increase in A β levels in BPA exposed mice.The authors acknowledged that their shortcomings may have been due to factors such as a limited sample size, as previous studies had seen increased APP or A β levels after BPA exposure. Overall, they were able to link increased Base1 expression and NF- κB expression with maternal BPA consumption.
A final interesting note from the researchers involved a potential link between Alzheimer’s disease and autism. Previously published research has shown similar instances of overlapping between BPA affected pathways and gene dysfunction associated with autism. Presumably by transitive law, researchers predicted pathways involved in Alzheimer’s may be associated with pathways involved with Autism. This discovery opens another possible line of research.
Despite relative shortcomings of their findings, the results described in “Prenatal exposure to bisphenol A alters the transcriptome-interactome profiles of genes associated with Alzheimer’s disease in the offspring hippocampus” set the stage for more necessary BPA research. Aside from further investigating the effect of increased Base1 and NF- κB expression, if a level of BPA defined by the FDA as not harmful can cause dysfunction of pathways also associated with Alzheimer’s disease, then it is essential the chemical is further investigated. Ultimately, though their research was not fully conclusive, a potential association between fetal exposure to BPA and Alzheimer’s disease in males was presented.
Emma Heiderscheit is a sophomore biology major at Davidson College. Contact her at: emheiderscheit@davidson.edu
References
Brent A. Bauer, M. D. (2019, December 18). Tips to reduce BPA exposure. Mayo Clinic. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/expert-answers/bpa/faq-20058331.
National Institutes of Health. (n.d.). ToxTutor – NOAEL and LOAEL. U.S. National Library of Medicine.https://toxtutor.nlm.nih.gov/02-006.html
Sukjamnong, S., Thongkorn, S., Kanlayaprasit, S., Saeliw, T., Hussem, K., Warayanon, W., … Sarachana, T. (2020, June 11). Prenatal exposure to bisphenol A alters the transcriptome-interactome profiles of genes associated with Alzheimer’s disease in the offspring hippocampus. Nature News. https://www.nature.com/articles/s41598-020-65229-0.
