Recently, I have begun to think about the role that exposure plays on behavioral health and human neurobiology. Chemical and psychological stress can induce changes in the brain’s ability to properly function, which can lead to long-term psychiatric consequences. That’s why I decided to attend the Distinguished Toxicology Scholar Award Lecture titled “Neurotoxicity and Neuroinflammation Profiles in Animal Models: A Brief Review of Some Unexpected Response Modifiers of Likely Relevance to Toxicology.”
When 2024 SOT Distinguished Toxicology Scholar Award recipient James P. O’Callaghan set out on his research career 40 years ago, he was a toxicologist—even if he didn’t know it at the time. As scientists, we often underestimate the value of variables that are outside the focus of the research we conduct, so Dr. O’Callaghan broke his lecture up into the “accidental discoveries” that drove his science to where it is now. He found that these underestimated and unexpected variables do indeed modulate toxic outcomes. With the help of his “co-conspirators,” Dr. O’Callaghan has contributed to work that was cited for a Nobel Prize, characterized classic neurotoxicants, and developed a model to study Gulf War Illness.
My biggest takeaway from Dr. O’Callaghan’s lecture is that neurotoxicology is complicated. The nervous system is filled with a multitude of cell types that each have targets of toxicity that are hard to predict and hard to find. By developing a “Neurotoxicity Toolbox” filled with potent neurotoxicants, Dr. O’Callaghan and his team have begun to elucidate the specific tissue, cellular, subcellular, and molecular mechanisms at play. Coupled with high-precision assays that “produce a positive signal against a negative background,” one can find damaged targets at sub-lethal concentrations.
Most impressive is Dr. O’Callaghan’s work on the relationship between amphetamine exposure, body temperature, and stress hormones. Increased body temperature and amphetamine administration was found to synergize and elevate markers of neurotoxicity and inflammation. By lowering the ambient temperature of mouse housing, Dr. O’Callaghan and his team found that markers of neurotoxicity and inflammation were ameliorated. Surprisingly, by subjecting the mice to mild stress by restraining them, core temperature of the rodents lowered, leading to neuroprotection from amphetamine treatment.
Dr. O’Callaghan’s talk left me inspired to ask more questions about how this work relates to my curiosity about behavioral and psychological health. I can only begin to understand what implications this data may have in the treatment of people with acute amphetamine overdoses and, furthermore, the relationship between neuroinflammation from chronic psychological stress and perhaps environmental factors that may help the body regulate stress. Only when such a person dedicates many years of their life to a cause are they able to create a talk as data rich and inspiring as Dr. O’Callaghan. Some of the best advice given during the talk was how crucial mentors are in advancing in the field: “If you have a great mentor like I did, it’s important to listen to her or him, they likely know more than you think they do.”
This blog reports on the Featured Session titled “Neurotoxicity and Neuroinflammation Profiles in Animal Models: A Brief Review of Some Unexpected Response Modifiers of Likely Relevance to Toxicology” that was held during the 2024 SOT Annual Meeting and ToxExpo. An on-demand recording of this session is available for meeting registrants on the SOT Online Planner and SOT Event App.
This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email SOT Headquarters.
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