Postprandial ghrelin response is reduced in patients with Parkinson’s disease and idiopathic REM sleep behaviour disorder: a peripheral biomarker for early Parkinson’s disease?

Abstract

Ghrelin, an orexigenic peptide, has multiple functions, which include promoting gastrointestinal motility and influencing higher brain functions. Experimental data suggest that ghrelin has neuroprotective potential in the MPTP mouse model of Parkinson's disease (PD). PD patients show delayed gastric emptying and other symptoms that may relate to disturbed excretion of ghrelin. No data are available on postprandial ghrelin response in patients with PD and idiopathic REM sleep behaviour disorder (iRBD)--a condition considered a putative preclinical stage of PD. We measured fasting and postprandial ghrelin serum concentrations in 20 healthy controls, 39 (including 19 drug-naïve) PD patients and 11 iRBD patients using a commercial radioimmunoassay for total ghrelin. For statistical analysis we employed ANCOVA and post-hoc testing with Bonferroni's method. Controls showed a decrease of mean fasting ghrelin serum concentrations in the early postprandial phase, followed by a recuperation starting 60 min after the test meal and reaching a maximum at 300 min. This recuperation was less pronounced in PD and iRBD; the slope of relative postprandial ghrelin recovery was different between the investigated groups (p = 0.007). Post-hoc testing showed a difference between controls and PD patients (p = 0.002) and between controls and iRBD patients (p = 0.037). The dynamic regulation of ghrelin in response to food intake is partially impaired in subjects at putative preclinical (iRBD) and clinical stages of PD. Reduced ghrelin excretion might increase the vulnerability of nigrostriatal dopaminergic neurons as suggested by animal studies. The impaired ghrelin excretion might qualify as a peripheral biomarker and be of diagnostic or therapeutic value.

Prokinetics stimulate the increase of ghrelin in mice

“…Although about a half of the patients suffering from Parkinson's disease experience reduced intestinal motility (29), it is likely because of decreased cholinergic and increased catecholaminergic stimulation (30), and dopaminergic medication (31). The study by Unger et al (32) pointed out the decrease in ghrelin signaling under this catecholaminergic and dopaminergic overstimulation, whereas it should be also noted that Karasawa et al (33) reported confl icting fi ndings in a similar experimental Parkinsonism model. Interestingly, no change in fasting ghrelin in vagotomized patients (34) suggests that disturbed cholinergic transmission is not a determinant for lowered ghrelin levels in Parkinson's disease.…”

Circulating unacylated-ghrelin impairs hippocampal neurogenesis and memory in mice and is altered in human Parkinson's disease dementia

“…http://dx.doi.org/10.1101/259333 doi: bioRxiv preprint first posted online Feb. 5, 2018; Mechanistically, we reasoned that as circulating levels of acyl-ghrelin and UAG have opposing actions on neurogenesis and cognition in mice, there should be a reduction in the plasma ratio of acyl-ghrelin to UAG (AG:UAG) in humans diagnosed with dementia. As acyl-ghrelin protects against neuron loss in models of Parkinson's disease (PD) 30,31 and is reportedly reduced in human PD 32,33 , we hypothesized that circulating AG:UAG ratios C.…”

Potential ghrelin-mediated benefits and risks of hydrogen water

“…The utility of ghrelin in Parkinson's models may reflect not only neuroprotection, but also an up-regulatory impact of ghrelin on dopamine synthesis and release in healthy neurons [59]. Decreased ghrelin secretion has been reported in patients with Parkinson's and Alzheimer's, and this might play a role not only in neurodegeneration, but also the weight loss that commonly accompanies these disorders [62][63][64]. A markedly decreased expression of both ghrelin and GOAT has been observed in the temporal lobe of Alzheimer's patients [65].…”