Bisphenol-A is a chemical used in plastic manufacturing which humans and animals are being exposed to in the environment. Bisphenol-A is an endocrine disruptor that has been reported to have negative effects on many biological systems. Dr Maya Frankfurt of the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, in collaboration with Dr Victoria Luine and Dr Rachel Bowman, has demonstrated that bisphenol-A has damaging effects on memory which could be due to decreased dendritic spine density.
Bisphenol-A (BPA) is a compound used for manufacturing hard plastics such as countertops, water bottles and microwaveable food containers. Leakage of BPA due to changes in temperature and pH has meant it is now detectable in the bodily fluids of both humans and animals. BPA leaches into food and drink when the products are packaged into BPA-containing materials.
Reported effects of BPA include alterations in the normal functioning of hormones such as oestrogen (the dominant female sex hormone) and testosterone (the dominant male sex hormone). BPA, which is an endocrine disrupter (a chemical which interferes with hormonal systems), could potentially cause a myriad of developmental and reproductive problems, as well as immune and neural effects. These negative effects have been well-documented in rodents during initial (after birth) development. However, given the extensive exposure of BPA during the lifespan there could be similar effects in humans and rodents during other periods of hormonal change such as adolescence, puberty, and adulthood. There is evidence that BPA imparts its effect via the oestrogen receptor, as well as other hormone receptors. Dr Frankfurt and collaborators have clearly demonstrated that oestrogen can enhance memory. If this is the case, and BPA can act via the oestrogen receptors, then how might BPA potentially affect memory?
Evidence of BPA’s effects
Traditionally BPA has been shown to affect reproductive behaviours. Recent studies indicate that BPA can also affect anxiety and depressive-like behaviours in rodents. Interestingly, administration of BPA before birth appears to increase anxiety and depressive-like behaviour in male, but not in female rats. However, it must be noted that females have been less well studied. This apparent sex difference was also true when BPA was administered to adolescent rats. BPA administered before birth was also found to worsen performance in memory-related tasks assigned to adolescent rodents – particularly in male rats, but also to a lesser degree in females. This discrepancy indicates that BPA may interact with testosterone and oestrogen differently.
Effects of BPA in adolescents
Adolescence is an intense period of hormonal change during which the brain undergoes significant alterations. Dr Frankfurt and her collaborators wanted to determine how BPA could affect memory during this transitional period. This is particularly relevant as adolescence is a period when the brain continues to sexually differentiate, and BPA is known to have sex-specific effects. Importantly, the dose of BPA used to examine the effect in adolescent rodents was below the safe limit specified by the United States Environmental Protection Agency for humans.
Exposure to BPA during adolescence caused significantly higher levels of anxiety in both male and female rats. Memory tasks, which assessed spatial memory and novel object recognition, were also assessed in the BPA-treated rodents. Both tasks involve areas of the brain which are used for memory (the hippocampus and prefrontal cortex). In these tasks, the rats were presented with two identical objects to investigate. Spatial memory was tested when one of the objects was moved to a different area, whereas novel object recognition was tested when one of the old objects was replaced. BPA administration was found to impair spatial memory in both sexes, and to impair novel object recognition in male rats more than females. The results from these studies show the concerning effects of exposure to a supposedly safe amount of BPA in rodents.
What about the long- term effects?
Reassuringly, the impairments on spatial memory and increased anxiety of BPA-treated adolescent rats were not found to persist into adulthood. However, the impairment of novel object recognition in males was found to persist.
The researchers were interested in determining the effect of BPA on female rats which no longer had their ovaries, as they would no longer be producing oestrogen. This experiment is important because oestrogen is increased during adolescence. If the effects of BPA were still found in these animals, then it suggests the effects were being mediated via oestrogen receptors. When BPA was given in adolescence, spatial memory was impaired at adolescence and adulthood. This result suggests that BPA action may be partially explained by oestrogen receptors.
BPA and cellular brain anatomy
Neurons are the cells of the brain which form connections, allowing all cognitive processes to be executed. This process is achieved in part via the formation of dendritic spines which receive information from many other neurons. The number of dendritic spines in the brain increases during cognitive development before reaching a stable level as the neural connections are established. However, many environmental factors during development, such as exposure to hormones, drugs or stress can affect the formation of dendritic spines, their turnover, and ultimately the neuronal network connections. Dendritic spine density is important as it essentially represents a brain’s potential for neural plasticity and is indicative of a brain’s ability to form memories.
The researchers showed that adolescent exposure to BPA decreased dendritic spine density in adolescent males and females in the hippocampus and prefrontal cortex. These changes could therefore be the means by which BPA impairs memory. However, this decrease only appeared to persist into adulthood in the hippocampus and not the prefrontal cortex. The deleterious effects of BPA on dendritic spine density were also tested in female rats with no intact ovaries. The decrease in these females was not found in adolescence but was found in adulthood. Therefore, some of the negative effects of BPA may not be mediated by oestrogen but instead by other hormones. It has been hypothesised by Dr Frankfurt and her research team that the effects on dendritic spine density could be due to disruption of oestrogen-mediated control of proteins, required for dendritic spine development during adolescence. The effect of oestrogen in female rats who have no ovaries was to increase dendritic spine density, but not to improve memory in tasks during adolescence. The group’s results therefore produce a complicated picture of the effects of BPA and indicate that the timing of BPA treatment is vital.
This work is extremely important because of the widespread use of manufactured plastics which contain BPA. BPA is present not only in the bodily fluids of animals but also in humans. Demonstration of the negative effects of BPA has resulted in policy change in many countries. The importance of this research cannot be underestimated as it provides us with information crucial to understanding BPA’s effects. Future work should focus on further elucidating the effects of BPA across all physiological systems in animals and humans. This information could then guide governments and organisations about safe levels of BPA, which may differ from the current recommendation.
- Frankfurt, M., Luine, V., & Bowman, R.E. (2020). Chapter Thirteen – A potential role for dendritic spines in bisphenol-A induced memory impairments during adolescence and adulthood. Vitamins and Hormones, 114, 307-329. Available at: https://doi.org/10.1016/bs.vh.2020.04.004
- Luine, V. & Frankfurt, M. (2020). Estrogenic regulation of memory: The first 50 years. Hormones and Behaviour, 121, 104711. Available at: https://doi.org/10.1016/j.yhbeh.2020.104711
- Bowman, R.E., Hagedorn, J., Madden, E., & Frankfurt, M. (2019). Effects of adolescent Bisphenol-A exposure on memory and spine density in ovariectomized female rats: Adolescence vs adulthood. Hormones and Behaviour, 107, 26-34. Available at: https://doi.org/10.1016/j.yhbeh.2018.11.004
- Bowman, R.E., Luine, V., Weinstein, S.D., Khandaker, H., DeWolf, S., & Frankfurt, M. (2015). Bisphenol-A exposure during adolescence leads to enduring alterations in cognition and dendritic spine density in adult male and female rats. Hormones and Behaviour (69), 89-97. Available at: https://doi.org/10.1016/j.yhbeh.2014.12.007
- Frankfurt, M. & Luine, V. (2015). The evolving role of dendritic spines and memory: Interaction(s) with oestradiol. Hormones and Behaviour, 74, 28-36. Available at: https://doi.org/10.1016/j.yhbeh.2015.05.004
Dr Maya Frankfurt explores the effects of bisphenol-A on various biological systems, with a particular concern for its effects on memory and neural structure.
- National Institutes of Health; CUNY collaborative research program (MF, VL)
- Sacred Heart University Undergraduate Research Grants (RB)
- Dr Victoria Luine: www.hunter.cuny.edu/psychology/people/faculty/physiological/inactive/luine
- Dr Rachel Bowman: https://works.bepress.com/rachel_bowman/
Dr Maya Frankfurt is a neuroscientist interested in neural plasticity and behaviour. Her research has focused on how neuronal structures are altered after exposure to oestrogen and bisphenol-A, and how these changes may underlie alterations in memory and other behaviours.