Researchers at the University of Swansea have discovered the gut hormone ghrelin is a key regulator of the formation of new nerve cells in the brain and have associated the hormone with the development of dementia in humans, specifically dementia caused by Parkinson’s disease.
Four out of every 5 patients diagnosed with Parkinson’s disease will develop dementia and approximately three quarters of patients will suffer weight loss due to Parkinson’s disease, with the weight loss linked to cognitive impairment and other symptoms not suffered by patients who do not experience weight loss, such as hallucinations.
The researchers investigated the potential role the gut hormone ghrelin may play in this process. Ghrelin is known as the hunger hormone, as levels in the blood increase when a patient when a patient has gone without food and decrease after a meal.
There are two forms of the hormone ghrelin – acyl-ghrelin (AG) and unacetylated ghrelin (UAG), with the former known to promote brain cell formation.
The researchers explained that circulating factors enhance and impair neuronal plasticity and learning in adult mammals, but the mechanisms involved are not well understood. They studied UAG modulated hippocampal plasticity and memory function to determine whether the levels of AG and UAG in the plasma were associated with the development of dementia in humans.
In studies on mice, the researchers found higher levels of UAG were associated with a reduction in hippocampal neurogenesis and brain plasticity. AG was found to reverse spatial memory impairment in mice.
The researchers collected blood samples from patients with Parkinson’s disease who had dementia or were cognitively intact, along with blood samples from a control group of patients without Parkinson’s disease and studied circulating AG:UAG levels. They found there was only a reduction in the AG:UAG ratio in patients in the Parkinson’s disease group with dementia.
“Hippocampal ghrelin-receptor expression remained unchanged; however, GOAT+ cell number was reduced in PDD. We identify UAG as a regulator of hippocampal-dependent plasticity and spatial memory and AG:UAG as a putative circulating diagnostic biomarker of dementia,” noted the researchers in the paper.
The AG:UAG ratio could therefore potentially serve as a biomarker that could be used to determine the onset of dementia in Parkinson’s disease patients. Ghrelin could also potentially be a new target in novel therapies for the disease.
You can read more about the study in the paper – Unacylated-Ghrelin Impairs Hippocampal Neurogenesis and Memory in Mice and Is Altered in Parkinson’s Dementia in Humans – which was recently published in the journal Cell Reports. DOI: 10.1016/j.xcrm.2020.100120