Congratulations to AAAS Mass Media fellows

Two Emory graduate students, Anzar Abbas and Katie Strong, will be spending the summer testing their communication skills as part of the AAAS Mass Media fellowship program. The program is supposed to promote science communication by giving young scientists a taste of what life is like at media organizations around the country. Both of Emory's fellows have already gained some experience in this realm. Abbas, a Neuroscience student who recently joined brain imaging number cruncher Shella Keilholz's lab, will be at Howard Hughes Medical Institute. He is part of the group that recently revived the Science Writers at Emory publication In Scripto. Strong, a Chemistry student working with Dennis Liotta on selective NMDA receptor drugs, will be at the Sacramento Bee. She has been quite prolific at the American Journal of Bioethics Neuroscience and its Neuroethics Blog. (Thanks to Ian Campbell, a previous AAAS Mass Media fellow from Emory, for notifying me on this!)

Risk triangle: immune gene, insecticide, Parkinson's

Genetic variation and exposure to pesticides both appear to affect risk for Parkinson's disease. A new study has found a connection between these two risk factors, in a way that highlights a role for immune responses in progression of the disease. The results are published in the inaugural issue of NPJ Parkinson's Disease. The findings implicate a type of pesticide called pyrethroids, which are found in the majority of commercial household insecticides, and are being used more in agriculture as other insecticides are being phased out. Although pyrethroids are neurotoxic for insects, exposure to them is generally considered safe for humans by federal authorities. The study is the first making the connection between pyrethroid exposure and genetic risk for Parkinson's, and thus needs follow-up investigation, says co-senior author Malu Tansey, PhD, associate professor of physiology at Emory University School of Medicine. The genetic variation the team probed, which has been previously tied to Parkinson's in larger genome-wide association studies, was in a non-coding region of a MHC II (major histocompatibility complex class II) gene, part of a group of genes that regulate the immune system. "We did not expect to find a specific association with pyrethroids," Tansey says. "It was known that acute exposure to pyrethroids could lead to immune dysfunction, and that the molecules they act on can be found in immune cells; now we need to know more about how longer-term exposure affects the immune system in a way that increases risk for Parkinson's." "There is already ample evidence that brain inflammation or an overactive immune system can drive the progression of Parkinson's. What we think may be happening here is that environmental exposures may be altering some people's immune responses, in a way that promotes chronic inflammation in the brain." For this study, Emory investigators led by Tansey and Jeremy Boss, PhD, chair of microbiology and immunology, teamed up with Stewart Factor, DO, head of Emory's Comprehensive Parkinson's Disease Center, and public health researchers from UCLA led by Beate Ritz, MD, PhD. The first author of the paper is MD/PhD student George T. Kannarkat. The UCLA researchers used a California state geographical database covering 30 years of pesticide use in agriculture. They defined exposure based on proximity (someone's work and home addresses), but did not measure levels of pesticides in the body. Pyrethroids are thought to decay relatively quickly, especially in sunlight, with half-lives in soil of days to weeks. In a group of 962 people from California's Central Valley, a common MHC II variant combined with above-average exposure to pyrethroid pesticides to increase the risk of Parkinson's disease. The riskiest form of the gene (where an individual is carrying two risk alleles) was found in 21 percent of Parkinson's patients and 16 percent of controls. In this group, genes or pyrethroid exposure by themselves did not significantly increase Parkinson's risk, but together, they did. People with more-than-average exposure to pyrethroids and carrying the riskiest form of the MHC II gene had 2.48 times more risk for Parkinson's than less-exposed people with the least risky gene form. Exposure to other types of pesticides such as organophosphates or paraquat did not heighten risk in the same way. Larger genetic studies (some including Factor and his patients) have previously identified variations in MHC II genes as having connections to Parkinson's. Puzzlingly, the same genetic variants affect Parkinson's risk differently in Caucasian/European and Chinese populations. MHC II genes are highly variable between individual humans; that's why they play a big role in organ transplant matching. Other experiments showed that the genetic variant connected to Parkinson's is connected with immune cell function. In a group of 81 Parkinson's patients and control participants from Emory of European ancestry the immune cells from people who had the higher-risk MHC II gene variant studied in California displayed more MHC molecules on their surfaces, the researchers found. MHC molecules are central to the process of "antigen presentation," a driver for T cells to become activated and have the rest of the immune system get involved. Heightened expression of MHC II was present in resting cells from both Parkinson's patients and healthy controls; but greater responsiveness to immune challenges were observed in Parkinson's patients with the higher risk genotype. The authors conclude: "Our data suggest that cellular biomarkers (like MHC II activation) may prove more useful than soluble molecules in plasma and cerebrospinal fluid to identify individuals at risk for disease or for patient recruitment into neuroprotective trials testing immunomodulatory drugs."

Fragile X syndrome: building a case for a treatment strategy

Decision-making time in mice. Further progress along these lines may lead to a clinical trial.

smart drugs

Brain enhancement: can and should we do it?

The Emory Center for Ethics and Emory’s Neuroscience Graduate Program recently co-hosted a symposium discussing the ethics of brain-enhancing technologies, both electronic and pharmacological.

Georgia Tech biomedical engineer Steve Potter explained his work harnessing the behavior of neurons grown on a grid of electrodes. The neurons, isolated from rats, produce bursts of electrical signals in various patterns, which can be “tuned” by the inputs they receive.

“The cells want to form circuits and wire themselves up,” he said.

As for future opportunities, he cited the technique of deep brain stimulation as well as clinical trials in progress, including one testing technology developed by the company Neuropace that monitors the brain’s electrical activity for the purpose of suppressing epileptic seizures. Similar technology is being developed to help control prosthetic limbs and could also promote recovery from brain injury or stroke, he said. Eventually, electrical stimulation that is not modulated according to feedback from the brain will be seen as an overly blunt instrument, even “barbaric,” he said.

Mike Kuhar, a neuroscientist at Yerkes National Primate Research Center, introduced the topic of cognitive enhancers or “smart drugs.” He described one particular class of proposed cognitive enhancers, called ampakines, which appear to improve functioning on certain tasks without stimulating signals throughout the brain. Kuhar questioned whether “smart drugs” pose unique challenges, compared to other types of drugs. From a pharmacology perspective, he said there is less distinction between therapy and enhancement, compared to a perspective imposed by regulators or insurance companies. He described three basic concerns: safety (avoiding toxicity or unacceptable side effects), freedom (lack of coercion from governments or employers) and fairness.

“Every drug has side effects,” he said. “There has to be a balance between the benefits versus the risks, and regulation plays an important role in that.”

He identified antidepressants and treatments for attention deficit-hyperactivity disorder or the symptoms of Alzheimer’s disease as already raising similar issues. The FDA has designated mild cognitive impairment associated with aging as an open area for pharmaceutical development, he noted.

James Hughes, a sociologist from Trinity College and executive director of the Institute for Ethics and Emerging Technologies, welcomed new technologies that he said could not only treat disease, but also enhance human capabilities and address social challenges such as criminal rehabilitation. However, he did identify potential “Ulysses problems”, where users of new technologies would need to exercise control and judgment.

In contrast, historian and Judaic scholar Hava Tirosh-Samuelson, from Arizona State University, decried an “overly mechanistic and not culturally-based understanding of what it means to be human.” She described transhumanism as a utopian extension of 19th century utilitarianism as expounded by thinkers such as Jeremy Bentham.

“Is the brain simply a computational machine?” she asked.

The use of military metaphors – such as “the war on cancer” – in the context of mental illness creates the false impression that everything is correctable or even perfectable, she said.

Emory neuroscience program director Yoland Smith said he wants ethics to become a strong component of Emory’s neuroscience program, with similar discussions and debates to come in future years.

Posted on by Quinn Eastman in Neuro Leave a comment
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