Nav: Home

Scientists link 'hunger hormone' to memory in Alzheimer's study

September 03, 2019

Scientists at The University of Texas at Dallas have found evidence suggesting that resistance to the "hunger hormone" ghrelin in the brain is linked to the cognitive impairments and memory loss associated with Alzheimer's disease (AD).

The findings, based on observations of postmortem brain-tissue samples from Alzheimer's patients and on experiments with a mouse model of AD, also suggest a possible treatment strategy for the incurable neurodegenerative disorder that affects about 5.8 million older adults in the United States.

The research was published Aug. 14 as the cover article in the journal Science Translational Medicine.

"This is a proof-of-concept study, but we are very encouraged by the results," said Dr. Heng Du, associate professor of biological sciences at UT Dallas and corresponding author of the study.

Produced in the stomach, ghrelin sends signals to the brain that regulate energy balance and body weight. Often called the hunger hormone, it plays a role in appetite and meal initiation. But ghrelin also has been implicated in learning and memory.

The hippocampus region of the brain -- crucial to learning, memory and emotions -- is one of the first to suffer cell death and damage in Alzheimer's disease due to a toxic buildup of protein fragments called amyloid beta.

In a healthy hippocampus, ghrelin binds with proteins called ghrelin receptors, which combine with similarly activated receptors for the neurotransmitter dopamine. The two receptors then form a protein complex that helps maintain communication between brain cells and, ultimately, memory.

In the new study, Du and his colleagues found that amyloid beta binds to ghrelin receptors in the hippocampus, blocking their ability to combine with dopamine receptors.

"Our hypothesis is that this dissociation between ghrelin and dopamine receptors may be what is affecting cognition in Alzheimer's patients," Du said. "As the brain loses the function of ghrelin receptors due to amyloid beta, the body tries to compensate by increasing the production of ghrelin and the number of ghrelin receptors. But the amyloid prevents the receptors from functioning."

Du likened the condition to insulin resistance found in individuals with type 2 diabetes. In that disease, insulin receptors malfunction.

"To compensate, patients in the early stages of type 2 diabetes produce more insulin to bind insulin receptors," Du said. "But they become insulin-resistant. No matter how much insulin your body produces, the insulin receptors are unable to activate the downstream biochemical reactions needed to transport glucose from blood into cells.

"Similarly, based on our findings, Alzheimer's might be linked to ghrelin resistance."

Du said the new findings help explain why a recent clinical trial of a compound called MK0677 -- designed to activate ghrelin receptors in the brain -- proved unable to slow the progression of Alzheimer's.

To test a different approach in their mouse model of AD, Du's team gave the mice MK0677 and another compound -- SKF81297 to activate dopamine receptors -- at the same time.

"When we gave these compounds simultaneously, we saw improved cognition and memory in the AD mice, and lesions in the hippocampus were reduced," Du said. "Activating both receptors at the same time was key; it restored the receptors' ability to form complexes. When this happens, we suspect the ghrelin receptor becomes protected and can no longer bind to amyloid beta.

"More research is needed, but targeting this mechanism might prove therapeutically useful."

Du, who has filed for a patent on the approach, said the team's findings suggest that Alzheimer's might be more than just a brain disease.

"As we age, we tend to experience changes in metabolism. These affect the heart and the gastrointestinal system, but maybe they also are affecting the brain by altering the ghrelin receptor," he said. "We know that even in the absence of dementia, many older people have memory problems, and this could be related to the dissociation between the receptors in the brain, even without the presence of amyloid.

"I'm starting to think of Alzheimer's as a systemic disorder, and that we should pay more attention to the metabolic and hormonal path of the disease."
-end-
Other UT Dallas researchers involved in the study were co-lead authors Jing Tian, doctoral student in molecular and cell biology, and Dr. Lan Guo, research assistant professor of biological sciences; Dr. Sven Kroener, associate professor of behavioral and brain sciences, and his doctoral students Christopher Driskill and Aarron Phensy; Esha Gauba, doctoral student in molecular and cell biology; and visiting scholars Dr. Shaomei Sui and Dr. Qi Wang.

Additional authors include Dr. Jeffrey Zigman, professor of internal medicine at UT Southwestern Medical Center, and Dr. Russell Swerdlow, director of the University of Kansas Alzheimer's Disease Center and the University of Kansas Medical Center Neurodegenerative Disorders Program.

The research was funded by the National Institutes of Health and the Alzheimer's Association.

University of Texas at Dallas

Related Diabetes Articles:

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
New oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes
A University of Colorado Anschutz Medical Campus study finds sotagliflozin helps control glucose and reduces the need for insulin in patients with type 1 diabetes.
More Diabetes News and Diabetes Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...