A gut hormone, ghrelin, is a key regulator of new nerve cells in the adult brain, a Swansea-led research team has discovered. It could help pave the way for new drugs to treat dementia in patients with Parkinson's Disease.
Blood-borne factors such as hormones regulate the process of brain cell formation - known as neurogenesis - and cognition in adult mammals.
The research team focused on the gut hormone acyl-ghrelin (AG), which is known to promote brain cell formation. A structure change to the hormone results in two distinct forms: AG and unacylated-ghrelin (UAG).
The team, led by Dr Jeff Davies of Swansea University Medical School, studied both AG and UAG to examine their respective influences over brain cell formation.
This research is relevant to Parkinson's as a large proportion of those with the disease experience dementia, which is linked to a loss of new nerve cells in the brain. This loss leads to a reduction in nerve cell connectivity, which plays a vital role in regulating memory function.
The team's key overall findings were:
- the UAG form of ghrelin reduces nerve cell formation and impairs memory
- Individuals diagnosed with Parkinson's disease dementia have a reduced AG:UAG ratio in their blood
Dr Jeff Davies of Swansea University Medical School, lead researcher, said:
"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.
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 team included collaborators from Newcastle University (UK) and Monash University (Australia). They examined the role of AG and UAG in the brain, and also compared blood collected from Parkinson's disease patients diagnosed with dementia with cognitively intact PD patients and a control group.
- Higher levels of UAG, using both pharmacological and genetic methods, reduced hippocampal neurogenesis and brain plasticity.
- AG helped reverse spatial memory impairments
- UAG blocks the process of brain cell formation prompted by AG
- The Parkinson's patients with dementia were the only one of the three patient groups examined to show a reduced AG:UAG ratio in their blood.
The research was published in Cell Reports Medicine.
Notes to Editors:
Swansea University is a world-class, research-led, dual campus university offering a first-class student experience and has one of the best employability rates of graduates in the UK. The University has the highest possible rating for teaching - the Gold rating in the Teaching Excellence Framework (TEF) in 2018 and was commended for its high proportions of students achieving consistently outstanding outcomes.
Swansea climbed 14 places to 31st in the Guardian University Guide 2019, making us Wales' top ranked university, with one of the best success rates of graduates gaining employment in the UK and the same overall satisfaction level as the Number 1 ranked university.
The 2014 Research Excellence Framework (REF) 2014 results saw Swansea make the 'biggest leap among research-intensive institutions' in the UK (Times Higher Education, December 2014) and achieved its ambition to be a top 30 research University, soaring up the league table to 26th in the UK.
The University is in the top 300 best universities in the world, ranked in the 251-300 group in The Times Higher Education World University rankings 2018. Swansea University now has 23 main partners, awarding joint degrees and post-graduate qualifications.
The University was established in 1920 and was the first campus university in the UK. It currently offers around 350 undergraduate courses and 350 postgraduate courses to circa 20,000 undergraduate and postgraduate students. The University has ambitious expansion plans as it moves towards its centenary in 2020 and aims to continue to extend its global reach and realise its domestic and international potential.
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Cell Reports Medicine