Environmental Factor – May 2022: Advances in Neurotoxicology Highlighted at NIEHS Workshop

Hollander’s research background includes the use of genetic, behavioral, electrophysiological, and pharmacological methods to study drug addiction and obesity. (Photo courtesy of Steve McCaw/NIEHS)

During a workshop titled “Modernizing Neurotoxicology at NIEHS: From Technologies to Applications in Environmental Health Sciences,” experts shared state-of-the-art research tools they believe will lead to a better understanding of how pollutants affect the brain and influence diseases. Held April 19-20, the event included 17 presentations on topics ranging from advances in neuroimaging to in vitro Approaches (cell-based) in developmental neurotoxicology.

“As the primary federal agency supporting medical and behavioral research for the nation, it is essential that the NIH [the National Institutes of Health] keeps pace with recent scientific advances,” said event organizer Jonathan Hollander, Ph.D., program director in the NIEHS Genes, Environment, and Health Branch. “It is important to examine the applicability of modern neuroscience approaches to toxicological research.”

Emerging Technology, Improved Capabilities

The objectives of the workshop were to review advances in neurological research, including new tools and lessons learned; identify key environmental health issues that would benefit from the use of these methods; and develop a strategy to encourage the adoption of emerging technologies. The conference consisted of the following four sessions.

  • “Advances in Neuroimaging,” chaired by Robert Sills, DVM, Ph.D., NIEHS Division of the National Toxicology Program (DNTP), and Kimberly Gray, Ph.D., Population Health Branch of the institute.
  • In vitro Approaches in Developmental Neurotoxicology Research,” chaired by Christopher McPherson, Ph.D., of DNTP, and Shannah Witchey, Ph.D., a former DNTP intern who now works for the pharmaceutical company Inotiv.
  • “Chemogenetics, Optogenetics, and Fiber Photometry to Advance Neurotoxicology,” chaired by Hollander and Jesse Cushman, Ph.D., of the NIEHS Neurobehavioral Core Laboratory.
  • “Emerging Spatial Technologies,” chaired by Jian-Liang Li, Ph.D., of the NIEHS Integrative Bioinformatics Support Group, and Benedict Anchang, Ph.D., of the biostatistics and computational biology branch of the institute.
Robert Sills, DVM, Ph.D., and Kimberly Gray, Ph.D. Sills, left, and Gray, right, moderated a 45-minute panel discussion at the end of the session they chaired, sparking lively conversation among the presenters. (Photos courtesy of Steve McCaw/NIEHS)

Meeting public health challenges

“Adoption of the technology discussed in this workshop will require greater collaboration between neuroscientists and environmental health scientists,” noted Rick Woychik, Ph.D., director of the NIEHS and the National Toxicology Program. “There is a critical need to use state-of-the-art research methods to advance our understanding of the neurotoxicological effects of environmental exposures,” he added.

“The NIEHS has a particular interest in neuroscience and neurotoxicology in particular,” said DNTP Scientific Director Brian Berridge, DVM, Ph.D. significant not only to developmental neurological diseases, but also to chronic progressive diseases,” he told attendees. Berridge added that the environmental health science community should aim to increase the adoption of new technologies and research capabilities that will address this public health challenge.

Shedding Light on Autism

Mark Shen, Ph.D. Shen is an assistant professor in the UNC School of Medicine and appointments to the Department of Psychiatry, the UNC Center for Neuroscience, and the Carolina Institute for Developmental Disabilities. (Photo courtesy of Mark Shen)

A method of identifying early autism risk markers called longitudinal neuroimaging generated significant interest and discussion at the conference. In his laboratory at the University of North Carolina at Chapel Hill (UNC), Mark Shen, Ph.D.uses magnetic resonance imaging (MRI) in infants and mouse models to identify the biological origins of neurodevelopmental disorders and to test potential therapies.

With funding from the NIH, Dr. Shen’s team is following 500 infants who are part of the Infant Brain Imaging Study. Using MRIs taken at 6, 12 and 24 months, along with other phenotypic data, he and his collaborators aim to determine what factors indicate whether a baby will receive an autism diagnosis.

“MRI-detectable brain changes in the first year of life actually precede the onset of behavioral symptoms and may predict later autism outcomes,” Shen said.

Recent research shows that accelerated brain growth between 6 and 12 months is an indicator of autism, according to Shen. Another indicator during this period is accelerated growth of the amygdala, an area of ​​the brain involved in interpreting the emotional meaning of our environment. Other markers of autism include impaired connections between brain regions and excess cerebrospinal fluid (CSF) surrounding the brain, Shen noted.

He added that over the next five years, his team will conduct NIH-funded clinical and preclinical studies to better understand CSF physiology and brain development in autism and related conditions.

Fluorescent sensors boost Parkinson’s disease research

Guohong Cui, MD, Ph.D. Last November, Cui hosted a distinguished NIEHS conference on the links between mitochondrial damage and Parkinson’s disease. (Photo courtesy of Steve McCaw/NIEHS)

One of the fundamental questions in neuroscience research is how our brains control behavior, a topic studied by Guohong Cui, MD, Ph.D., who leads the NIEHS In Vivo Neurobiology Group.

However, many of the existing techniques for assessing behavior are limited, according to Cui. He therefore uses multi-colored fiber photometry, a method that measures brain activity in rodent models.

Using genetically encoded fluorescent sensors, such as voltage, calcium and neurotransmitter sensors, researchers can observe different groups of neurons when mice engage in certain behaviors.

Cui studies Parkinson’s disease and the death of dopaminergic neurons, some of which are particularly vulnerable due to their existing calcium levels.

Learn more about Cui’s research.

Increase collaboration, adopt new tools

“I think it’s important that we establish more collaboration to break down the barriers between environmental health scientists and neuroscientists,” Gray said. “I think there are exciting opportunities for us to use the imaging tools and other technologies discussed at this conference to fill these gaps,” she added.

“I think those of us who are neuroscientists here at NIH have a perception that maybe the field could more quickly adopt and assimilate some of these modern tools,” said Cindy Lawler, Ph.D., head of the department. Genes, Environment, and NIEHS Health Branch. “When you bring people together and give them opportunities to share, the magic happens.”

(Susan Cozier is a contract writer for the NIEHS Office of Communications and Public Liaison.)