During the 2018 Annual Meeting and ToxExpo, I had the pleasure to participate in the Symposium Session “Mechanisms of Autophagic Function and Dysfunction in Neurotoxicity and Neurodegeneration,” organized by Johnny Wise, Purdue University, and his Co-Chair Dr. Aaron Bowman, Vanderbilt University Medical Center. It was a unique session because it was a Symposium where all the presenters were trainees.
The participants presented research projects where autophagy either played a role in protecting neuro-glial cells against the neurotoxic effects of environmental agents or it was contributing to cell demise. The presentations provided an enriching experience to the trainees and the entire audience as we were able to see different approaches to study autophagy and learn from its different roles in neuro-glial health and survival. It was very interesting to discover how a dynamic process like autophagy responds in very different ways to toxins or diseases in the brain.
In 2016, the Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi for “discoveries of the mechanisms for autophagy.” The term autophagy, which comes from Greek, meaning “eating of self,” is a homeostatic process in which components of the cell are degraded in order to produce energy or preserve cellular homeostasis and survival. In recent years, there has been an advance in knowledge about the role of autophagy in neurotoxicology events.
I had the pleasure to open the Scientific Session by discussing the role of autophagy in arsenic (As) toxicity in a model of primary cortical astrocytes, where we found that autophagy activation seems to activate cell death in As toxicity. Using an approach to inhibit the autophagy pathway, it was shown that the cells were protected against apoptotic cell death.
The second presentation was about autophagy disruption in a model of manganese (Mn) exposure and its relationship with mitochondria dysfunction, also in primary astrocytes. Ziyan Zhang, Albert Einstein College of Medicine, showed how different signaling pathways are involved in the response of the cells to Mn toxicity. Continuing with Mn, Miles Bryan, Vanderbilt University Medical Center, explained the role of this essential metal and the importance of addressing its imbalance in Huntington’s disease (HD). Mr. Bryan described how Mn alters autophagy and the complex relationship of Mn uptake and autophagy pathway in HD.
Mr. Wise discussed how the ubiquitin binding protein optineurin, associated with glaucoma, has the potential to be used as a marker for Parkinson’s disease (PD). He used the in vivo model of rotenone treatment (a mitochondrial toxin) to generate a Parkinsonian phenotype in rats to evaluate the accumulation of optineurin in dopaminergic neurons during degeneration. Adhithiya Charli, Iowa State University, discussed the role of the pesticide endosulfan, environmental exposure to which is considered a risk for PD, and presented results regarding the interplay between apoptosis and autophagy in dopaminergic neuronal cell. To close the session, Georgina Harris, Johns Hopkins Center for Alternatives to Animal Testing, continued with the discussion of PD. She used a novel in vitro 3D model and studied the effects of rotenone. Ms. Harris showed the persistent activation of autophagy even after the removal of the rotenone and its important function in dopaminergic cell degeneration.
Overall, the session had great topics of discussion; the audience asked very interesting and critical questions, and it was an excellent forum for feedback and exchange of ideas with the audience.
This blog was prepared by an SOT Reporter. SOT Reporters are SOT members who volunteer to write about sessions and events they attend during the SOT Annual Meeting and ToxExpo. If you are interested in participating in the SOT Reporter program in the future, please email SOT Communications Director Michelle Werts.