One common physiological phenomenon that is involved both in infectious and in malignant processes is the reduction in appetite: disease anorexia. An increase in plasma levels of leptin with inflammation is thought to be involved in this process. However, from an evolutionary perspective, in certain cases, it would be more adaptive for an internal parasite to stimulate the appetite of the host instead of causing its suppression.
We tested whether a parasitic infection with the larvae of the helminth parasite Taenia taeniaformis affects the levels of appetite-regulating proteins, such as leptin, ghrelin and neuropeptide-Y (NPY) in wild yellow-necked mouse (Apodemus flavicollis). We found that infected mice had lower plasma levels of leptin and increased levels of NPY than the uninfected subjects. Ghrelin levels were not associated with the occurrence of the parasites; however, these levels strongly correlated with the levels of NPY. This study suggests a possible manipulation by parasitic larvae of appetite regulation in infected subjects.
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.
Connie’s notes: Many Parkinson’s and Alzheimer’s clients of Motherhealth caregivers love ice cream in the middle of the night. They are hungry at night.