A team of researchers headed by Swansea University has discovered that a gut hormone, called ghrelin, is a crucial regulator of new nerve cells that form in the adult brain. The findings could lead to the development of novel drugs for treating dementia in patients affected by Parkinson’s disease.
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Blood-borne factors, like hormones, control the process of the formation of brain cells—called neurogenesis—and also regulate cognition in adult mammals.
The researchers focused on acyl-ghrelin (AG), the gut hormone known to support the formation of brain cells. A structural modification of the hormone leads to two distinct forms—unacylated-ghrelin (UAG) and AG.
Headed by Dr. Jeff Davies from Swansea University Medical School, the researchers examined both UAG and AG to study their respective influences over the formation of brain cells.
The study is relevant to Parkinson’s disease because of a large number of people affected by this disease experience dementia, which is associated with a loss of new nerve cells in the brain. This loss results in reduced connectivity of nerve cells, which plays a crucial role in controlling memory function.
The major overall findings of the researchers were:
- The UAG form of ghrelin decreases the formation of nerve cells and impairs memory function
- People diagnosed with Parkinson’s disease dementia have a decreased ratio of AG: UAG in their blood
Our work highlights the crucial role of ghrelin as a regulator of new nerve cells in the adult brain, and the damaging effect of the UAG form specifically. This hormone represents an important target for new drug research, which could lead ultimately to better treatment for people with Parkinson’s.”
Dr Jeff Davies, Lead Researcher, Swansea University Medical School
Dr. Davies continued, “Our findings show that the AG: UAG ratio could also serve as a biomarker, allowing earlier identification of dementia in people with Parkinson’s disease.”
The research team included colleagues from Newcastle University in the United Kingdom and Monash University in Australia. They investigated the function of UAG and AG in the brain and also compared the blood collected from patients with Parkinson’s disease and diagnosed with dementia with patients who have cognitively intact PD and also with a control group.
The researchers found:
- AG helped reverse impairments in spatial memory
- Higher concentrations of UAG, using both genetic and pharmacological techniques, decreased brain plasticity and hippocampal neurogenesis
- UAG inhibits the process of brain cell formation induced by AG
- Parkinson’s patients diagnosed with dementia were the only one among the three patient groups examined to exhibit a reduced ratio of AG: UAG in their blood
The study was published in the Cell Reports Medicine journal.
Hornsby, A. K. E., et al. (2020) Unacylated-Ghrelin Impairs Hippocampal Neurogenesis and Memory in Mice and Is Altered in Parkinson’s Dementia in Humans. Cell Reports Medicine. doi.org/10.1016/j.xcrm.2020.100120.