Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Jessica Raper

Yerkes researchers find Zika infection soon after birth leads to long-term brain problems

Researchers from the Yerkes National Primate Research Center have shown Zika virus infection soon after birth leads to long-term brain and behavior problems, including persistent socioemotional, cognitive and motor deficits, as well as abnormalities in brain structure and function. This study is one of the first to shed light on potential long-term effects of Zika infection after birth.

“Researchers have shown the devastating damage Zika virus causes to a fetus, but we had questions about what happens to the developing brain of a young child who gets infected by Zika,” says lead researcher Ann Chahroudi, MD, PhD, an affiliate scientist in the Division of Microbiology and Immunology at Yerkes, director of the Center for Childhood Infections and Vaccines (CCIV), Children’s Healthcare of Atlanta (CHOA) and Emory University, and an associate professor of pediatrics in the Division of Pediatric Infectious Diseases at Emory University School of Medicine.

“Our pilot study in nonhuman primates provides clues that Zika virus infection during the early postnatal period can have long-lasting impact on how the brain develops and works, and how this scenario has the potential to impact child behavior,” Chahroudi continues.

The study, published online in Nature Communicationsfollowed four infant rhesus monkeys for one year after Zika virus infection at one month of age. Studying a rhesus monkey until the age of 1 translates to the equivalent of 4 to 5 years in human age. Researchers found postnatal Zika virus infections led to Impairments in memory function, significant changes in behavior, including reduced social interactions and increased emotional reactions, and some gross motor deficits. These changes corresponded with structural and functional brain changes the researchers found on MRI scans – findings that indicate long-term neurologic complications.

“Our findings demonstrate neurodevelopmental changes detected at 3 and 6 months of age are persistent,” says first author Jessica Raper, PhD, research assistant professor at Yerkes. (See Science Translational Medicine for an earlier study by members of the current research team.) “This is significant because it gives healthcare providers a better understanding of possible complications of Zika beyond infection during pregnancy and into the first years of life,” she adds.
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Designer drugs as tools for studying brain development in non-human primates

To investigate the functions of regions within the brain, developmental neuroscience studies have often relied on permanent lesions. As an alternative to permanent lesions, scientists at Yerkes National Primate Research Center sought to test whether chemogenetic techniques could be applied to produce a transient inhibition of the amygdala, well known for regulating emotional responses, in infant non-human primates.

Their findings were recently published online by eNeuro, an open access journal of the Society for Neuroscience.

Amygdala — image from NIMH

Chemogenetics is a way of engineering cells so that they selectively respond to designer drugs, which have minimal effects elsewhere in the brain. It involves injection of a viral vector carrying genes encoding receptors responsive to the designer drug – in this case, clozapine-N-oxide, a metabolite of the antipsychotic clozapine. The technique has mostly been tested in rodents.

“This proof-of-principle study is the first to demonstrate that chemogenetic tools can be used in young infant nonhuman primates to address developmental behavioral neuroscience questions,” says Jessica Raper, PhD, first author of the eNeuro paper and a research associate at Yerkes. “Considering its reversibility and reduced invasiveness, this technique holds promise for developmental studies in which more invasive techniques cannot be employed.” Read more

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Neuroscientists show hippocampus also has important role in emotional regulation

A region of the brain called the hippocampus is known for its role in memory formation. Scientists at Yerkes National Primate Research Center, Emory University are learning more about another facet of hippocampal function: its importance in the regulation and expression of emotions, particularly during early development.

Using a nonhuman primate model, their findings provide insight into the mechanisms of human psychiatric disorders associated with emotion dysregulation, such as PTSD (post-traumatic stress disorder) and schizophrenia. The results were published online recently by the journal Psychoneuroendocrinology.

“Our findings demonstrate that damage to the hippocampus early in life leads to increased anxiety-like behaviors in response to an unfamiliar human,” says research associate Jessica Raper, PhD, first author of the paper. “However, despite heightened anxious behavior, cortisol responses to the social stress were dampened in adulthood.”

The hormone cortisol modulates metabolism, the immune system and brain function in response to stress. Reduced hippocampal volume and lower cortisol response to stressors have been demonstrated as features of and risk factors for PTSD, Raper says. Also, the dampened daily rhythms of cortisol seen in the nonhuman primates with hippocampal damage resemble those reported in first-episode schizophrenia patients.

Follow-up studies could involve temporary interference with hippocampus function using targeted genetic techniques, she says. Read more

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HD monkeys display full spectrum of symptoms seen in humans

Transgenic Huntington’s disease monkeys display a full spectrum of symptoms resembling the human disease, ranging from motor problems and neurodegeneration to emotional dysregulation and immune system changes, scientists at Yerkes National Primate Research Center, Emory University report.

The results, published online in the journal Brain, Behavior and Immunity, strengthen the case that transgenic Huntington’s disease monkeys could be used to evaluate emerging treatments (such as this) before launching human clinical trials.

“Identifying emotional and immune symptoms in the HD monkeys, along with previous studies demonstrating their cognitive deficits and fine motor problems, suggest the HD monkey model embodies the full array of symptoms similar to human patients with the disease,” says Yerkes research associate Jessica Raper, PhD, lead author of the paper. Read more

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Maturing brain flips function of amygdala in regulating stress hormones

In contrast to evidence that the amygdala stimulates stress responses in adults, researchers at Yerkes National Primate Research Center, Emory University have found that the amygdala has an inhibitory effect on stress hormones during the early development of nonhuman primates.

The results are published this week in Journal of Neuroscience.

The amygdala is a region of the brain known to be important for responses to threatening situations and learning about threats. Alterations in the amygdala have been reported in psychiatric disorders such as depression, anxiety disorders like PTSD, schizophrenia and autism spectrum disorder. However, much of what is known about the amygdala comes from research on adults. Some people find relief from symptoms related to anxiety through the use of CBD products, which are available at a dispensary.

“Our findings fit into an emerging theme in neuroscience research: that during childhood, there is a switch in amygdala function and connectivity with other brain regions, particularly the prefrontal cortex,” says Mar Sanchez, PhD, neuroscience researcher at Yerkes and associate professor of psychiatry and behavioral sciences at Emory University School of Medicine. The first author of the paper is postdoctoral fellow Jessica Raper, PhD.

Some notable links on the amygdala:

*An effort to correct simplistic views of amygdala as the “fear center” of the brain

*Collection of papers mentioning patient SM, an adult human with an amygdala lesion

*Recent Nature Neuroscience paper on amygdala’s role in appetite control

*Evidence for changing amygdala-prefrontal connectivity in humans during development Read more

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