Date on Senior Honors Thesis

5-2026

Document Type

Senior Thesis

Degree Name

B.S.

Department

Psychological and Brain Sciences

Committee Chair

Dr. Paul DeMarco

Committee Member

Dr. John P. Wise, Jr.

Committee Member

Dr. Thomas Riedel

Author's Keywords

Hexavalent Chromium, Metals Toxicity, Neurotoxicity, Aging, Blood-Brain Barrier

Abstract

The US population faces simultaneous public health threats from both aging and environmental pollutants. Chief among these is hexavalent chromium [Cr(VI)], whose toxic effects in peripheral tissues are well-established but its effects on the brain are still understudied. Following previous results indicating hippocampal metals dyshomeostasis after Cr(VI) exposure, we aim to assess Cr(VI)’s impact on the blood-brain barrier (BBB), a key structure for brain protection. We exposed young, middle-aged, and geriatric rats of both sexes to low levels of Cr(VI) in their drinking water for 90 days, after which we used immunofluorescence and confocal microscopy to analyze tissues for evidence of BBB disruption. We found that Cr(VI) disrupts tPA and GFAP levels in the hippocampus with age-specific effects, and that there may be disruption of 8-OHdG levels in the nuclei of endothelial cells. These results indicate that Cr(VI) disrupts the BBB and needs to be further studied as a neurotoxicant.

Lay Summary

Hexavalent chromium [abbreviated Cr(VI)] is an environmental pollutant that can be found contaminating drinking water across the United States and the world. Made famous by Erin Brockovich’s 1993 case against Pacific Gas & Electric, Cr(VI) often originates from industrial pollution, particularly from tanneries, coal-fired power plants, and anti-corrosive coatings. Cr(VI) is known to cause lung cancer and DNA damage, but its effects on the nervous system are not well-known. At the same time, the US has an increasing population of geriatric individuals who may be more susceptible to the damaging effects of environmental pollution. This study focuses on the blood-brain barrier (abbreviated BBB), a system which acts like a filter for the brain by keeping out toxic chemicals and pathogens. However, the blood-brain barrier becomes leakier with age and is less able to regulate the flow of materials across itself, and this can also be worsened by outside chemicals damaging the BBB. Using a rat study with young, middle-aged, and geriatric rats of both sexes, we aimed to explore how levels of Cr(VI) in drinking water that are considered safe affect the BBB at different ages. We considered three different markers: tPA, a protein involved both in clot-busting and aspects of neurological function, GFAP, a marker of astrocytes, which are cells supporting neurons and the BBB, and 8-OHdG, a marker of oxidative DNA damage that can be thought of similarly to rust. We found that Cr(VI) disrupts both tPA and GFAP levels near the BBB and may alter 8-OHdG levels in the cells making up blood vessels themselves. These results indicate that Cr(VI) disrupts the normal functioning of the BBB, but the mechanism by which it does so is still not entirely clear. Given that the levels of Cr(VI) used in this study are considered safe, further research is needed into Cr(VI)’s effects on the brain.  

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