Mouse version of 3q29 deletion: insights into schizophrenia/ASD pathways

Emory researchers see investigating 3q29 deletion as a way of unraveling schizophrenia’s biological and genetic Read more

B cells off the rails early in lupus

Emory scientists could discern that in people with SLE, signals driving expansion and activation are present at an earlier stage of B cell differentiation than previously Read more

Head to head narcolepsy/hypersomnia study

At the sleep research meeting in San Antonio this year, there were signs of an impending pharmaceutical arms race in the realm of narcolepsy. The big fish in a small pond, Jazz Pharmaceuticals, was preparing to market its recently FDA-approved medication: Sunosi/solriamfetol. Startup Harmony Biosciences was close behind with pitolisant, already approved in Europe. On the horizon are experimental drugs designed to more precisely target the neuropeptide deficiency in people with classic narcolepsy type 1 Read more

David Weinshenker

Mouse version of 3q29 deletion: insights into schizophrenia/ASD pathways

Scientists at Emory University School of Medicine have created a mouse model of human 3q29 deletion syndrome, which is expected to provide insights into the genetic underpinnings of both schizophrenia and autism spectrum disorder.

In 3q29 deletion syndrome, a stretch of DNA containing several genes is missing from one of a child’s chromosomes. The deletion usually occurs spontaneously rather than being inherited. Affected individuals have a higher risk of developing intellectual disability, schizophrenia, and autism spectrum disorder. 3q29 deletion is one of the strongest genetic risk factors for schizophrenia, and the Emory researchers see investigating it as a way of unraveling schizophrenia’s biological and genetic complexity.

The results were published in Molecular Psychiatry.

“We see these mice as useful tools for understanding the parts of the brain whose development is perturbed by 3q29 deletion, and how it affects males and females differently,” says Jennifer Mulle, PhD, assistant professor of human genetics. “They are also a starting point for dissecting individual genes within the 3q29 deletion.”

Working with clinicians and psychologists at Marcus Autism Center, Mulle is leading an ongoing study of 3q29 deletion’s effects in humans, and observations from the mice are expected to inform these efforts. (More about Mulle here.) Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Looking ahead to new opioid treatments

Stephanie Foster sees herself one day specializing in addiction psychiatry. When she started her MD/PhD studies at Emory, she sought out neuroscientist David Weinshenker to discuss research projects. She is now examining potential treatments for opiate addiction based on galanin, a neuropeptide found in the brain.

Weinshenker and his colleagues had already been studying galanin in relation to stimulants such as cocaine. Preliminary studies in animals indicate that activating galanin signals might reduce the rewarding effects of opiates, withdrawal symptoms, and relapse-like behavior.

“This was a whole new direction that looked promising,” Foster says. “But first, we have to work out the brain circuitry.”

Foster comes from a Native American background, and has a long-range plan to work in the Indian Health Service. The death rate of Native Americans from opiate overdoses is the highest of any American population group, according to the Centers for Disease Control and Prevention. She would like to establish a research lab in a region of the country where she could continue her addiction research and also work closely with Native communities.

Screenshot from NIH reporter (grant database). F31 grants for year 2018.

Last year, Foster applied for and received an individual grant from the National Institute on Drug Abuse to support her work. Emory currently leads U.S. universities in the number of graduate students holding their own active grants from the National Institutes of Health. This reflects a multi-year effort to build instruction in critical parts of scientific life: planning and communicating about one’s work.

With opiate addiction, convincing others that the topic is worthwhile is not so difficult. Foster notes that few treatments are available for the early stages of opiate addiction. Long-lasting opiate substitutes/replacements such as methadone and buprenorphine are used once dependence has set in, and another medication, lofexidine, was recently approved for acute withdrawal symptoms.

“There isn’t really anything for people before they reach that stage,” Foster says. “Our idea is to look for an intervention that could be given earlier.” Read more

Posted on by Quinn Eastman in Neuro Leave a comment

The blue spot: where seeds of destruction begin

Neuroscientist and geneticist David Weinshenker makes a case that the locus coeruleus (LC), a small region of the brainstem and part of the pons, is among the earliest regions to show signs of degeneration in both Alzheimer’s and Parkinson’s disease. You can check it out in Trends in Neurosciences.

The LC is the main source of the neurotransmitter norepinephrine in the brain, and gets its name (Latin for “blue spot”) from the pigment neuromelanin, which is formed as a byproduct of the synthesis of norepinephrine and its related neurotransmitter dopamine. The LC has connections all over the brain, and is thought to be involved in arousal and attention, stress responses, learning and memory, and the sleep-wake cycle.

Cells in the locus coeruleus are lost in mild cognitive impairment and Alzheimer’s. From Kelly et al Acta Neuropath. Comm. (2017) via Creative Commons

The protein tau is one of the toxic proteins tied to Alzheimer’s, and it forms intracellular tangles. Pathologists have observed that precursors to tau tangles can be found in the LC in apparently healthy people before anywhere else in the brain, sometimes during the first few decades of life, Weinshenker writes. A similar bad actor in Parkinson’s, alpha-synuclein, can also be detected in the LC before other parts of the brain that are well known for damage in Parkinson’s, such as the dopamine neurons in the substantia nigra.

“The LC is the earliest site to show tau pathology in AD and one of the earliest (but not the earliest) site to show alpha-synuclein pathology in PD,” Weinshenker tells Lab Land. “The degeneration of the cells in both these diseases is more gradual. It probably starts in the terminals/fibers and eventually the cell bodies die.” Read more

Posted on by Quinn Eastman in Neuro Leave a comment

From Emory scientist to California policy analyst

Don’t call them alternative careers — since most graduate students in the biomedical sciences won’t end up as professors. Since I found a career outside the laboratory myself, I like to keep an eye out for examples of Emory people who have made a similar jump. [Several more in this Emory Magazine feature, which mentions the BEST program, aimed at facilitating that leap.]

Debra Cooper, PhD

Debra Cooper, PhD

After a postdoc in Texas, former Emory neuroscience graduate student Debra Cooper was awarded a California Council on Science and Technology fellowship to work with the California State Senate staff, and is now a policy consultant there. More about her work can also be found at the CCST blog.

Describe your position as policy consultant now. What types of things do you work on? How does your experience in neuroscience/drug abuse research fit in?

As a policy consultant at the California State Senate Office of Research, I function as a bridge between policy and the technical information that informs public policy. A large component of my time is spent translating research and linking it with relevant policies and regulations. I then synthesize this information and disseminate it to the appropriate audiences through memoranda, reports, or presentations. Sometimes this information is used to advise and make recommendations for legislative ideas.

My main assignments deal with human services (i.e., public services provided by governmental organizations) and veterans affairs. As such, not every project that I work on is directly related to neuroscience, but I often find overlap between my assignments and my academic background. For instance, the intersection of mental health and veterans affairs services is an important topic that bridges my backgrounds. Even when I’m working on issues that don’t directly link to mental health, the years that I spent analyzing research and statistics comes in handy when evaluating relevant documents.

Describe your graduate research at Emory.

I had co-advisors while working on my PhD at Emory – Drs. David Weinshenker and Leonard Howell. My dissertation research focused on one question answered with two different model animals: rats (Weinshenker lab) and squirrel monkeys (Howell lab). I was studying the effectiveness of a drug, nepicastat, in reducing rates of relapse to cocaine abuse. Nepicastat blocks an enzyme (dopamine beta-hydoxylase) which is crucial for converting the neurochemical dopamine into the neurochemical norepinephrine. Both of these neurochemicals are involved in responses to cocaine, and we hypothesized that nepicastat could help in regulating these neurochemicals to prevent relapse. Read more

Posted on by Quinn Eastman in Neuro, Uncategorized Leave a comment

Explainer: the locus coeruleus

The locus coeruleus is a part of the brain that has been getting a lot of attention recently from Emory neuroscience researchers.

The locus coeruleus is the biggest source of the neurotransmitter norepinephrine in the brain. Located deep in the brainstem, it has connections all over the brain, and is thought to be involved in arousal and attention, stress, memory, the sleep-wake cycle and balance.

Researchers interested in neurodegenerative disease want to look at the locus coeruleus because it may be one of the first structures to degenerate in diseases such as Alzheimer’s and Parkinson’s. In particular, the influential studies of German neuro-anatomist Heiko Braak highlight the locus coeruleus as a key “canary in the coal mine” indicator of neurodegeneration.

That’s why neurologist Dan Huddleston, working with biomedical imaging specialists Xiangchuan Chen and Xiaoping Hu and colleagues at Emory, has been developing a method for estimating the volume of the locus coeruleus by magnetic resonance imaging (MRI). Their procedure uses MRI tuned in such a way to detect the pigment neuromelanin (see panel), which accumulate in both the locus coeruleus and in the substantia nigra. Read more

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Study: Regular aerobic exercise and prevention of drug abuse relapse

Exercise provides health benefits

Researchers at Emory University and the University of Georgia have received funding from the National Institutes of Health to study the neurobiological mechanisms for how regular aerobic exercise may prevent drug abuse relapse. The grant is for $1.9 million over the next five years.

David Weinshenker, PhD, associate professor of human genetics, Emory School of Medicine, is a co-principal investigator on the project.

David Weinshenker, PhD

“This research will provide new insight into how regular exercise may attenuate drug abuse in humans,” Weinshenker says “More importantly, it may reveal a neural mechanism through which exercise may prevent the relapse into drug-seeking behavior.”

During the study, Weinshenker and UGA co-investigator Philip Holmes, professor of psychology in the Franklin College of Arts and Sciences, will measure exercise-induced increases of the galanin gene activity in the rat brain.

Read more

Posted on by sgoodwin in Uncategorized Leave a comment