Brain organoid model shows molecular signs of Alzheimer’s before birth

In a model of human fetal brain development, Emory researchers can see perturbations of epigenetic markers in cells derived from people with familial early-onset Alzheimer’s disease, which takes decades to appear. This suggests that in people who inherit mutations linked to early-onset Alzheimer’s, it would be possible to detect molecular changes in their brains before birth. The results were published in the journal Cell Reports. “The beauty of using organoids is that they allow us to Read more

The earliest spot for Alzheimer's blues

How the most common genetic risk factor in AD interacts with the earliest site of neurodegeneration Read more

Make ‘em fight: redirecting neutrophils in CF

Why do people with cystic fibrosis (CF) have such trouble with lung infections? The conventional view is that people with CF are at greater risk for lung infections because thick, sticky mucus builds up in their lungs, allowing bacteria to thrive. CF is caused by a mutation that affects the composition of the mucus. Rabindra Tirouvanziam, an immunologist at Emory, says a better question is: what type of cell is supposed to be fighting the Read more

galanin

Galanin: the ‘keep calm and carry on’ hormone?

A few celebrity neuropeptides have acquired a reputation – sometimes exaggerated — and a flavor, corresponding to their functions in the brain.

Oxytocin has the aura of a “cuddle hormone” because of its role in social bonding and reproduction. Endorphins are the body’s natural pain-killers, long thought to be responsible for “runner’s high.” Hypocretin/orexin, missing in narcolepsy, is a stabilizer of wakefulness as well as motivation.

Galanin, studied by Emory neuroscientist David Weinshenker’s lab, is not as flashy as other neuropeptides. While it is accumulating an intriguing track record, galanin appears to play subtly different roles depending on where it is expressed. It is tempting to call galanin the “keep calm and carry on” hormone, but the research on galanin is so complex it’s difficult to pin down.

Graduate student Rachel Tillage and colleagues have a paper this week in Journal of Neuroscience detailing how galanin’s production by one group of neurons in the brainstem confers stress resilience in mice.

This image shows the rough location for the locus coeruleus in the human brain. In mice, production of galanin in the locus coeruleus cushions against stress.

The new paper shows that exercise increases galanin in the locus coeruleus, a region in the brainstem that produces norepinephrine (important for attention, alertness, anxiety and muscle tone). Galanin can provide protection against the anxiety-inducing effects of artificial but very specific locus coeruleus activation by optogenetics.

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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 1 Comment

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.

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