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?
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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.
KeywordsParkinson’s disease REM sleep behaviour disorder (RBD) Ghrelin Vagal innervation, biomarker
This work was supported by a grant from the Michael J. Fox Foundation for Parkinson’s Research, USA (to M.M.U. and W.H.O.) and by resources of the BMBF-founded “Competence Network Parkinson”, Germany (to K.M.E. and W.H.O.).
Conflict of interest
All authors declare that there are no financial or personal relationships with other people or organisations that could inappropriately influence this work. The authors declare that there is no conflict of interest regarding this work.
- 1.Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, Roth RH, Sleeman MW, Picciotto MR, Tschop MH, Gao XB, Horvath TL (2006) Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J Clin Invest 116:3229–3239PubMedCrossRefGoogle Scholar
- 2.Andrews ZB, Erion D, Beiler R, Liu ZW, Abizaid A, Zigman J, Elsworth JD, Savitt JM, DiMarchi R, Tschoep M, Roth RH, Gao XB, Horvath TL (2009) Ghrelin promotes and protects nigrostriatal dopamine function via a UCP2-dependent mitochondrial mechanism. J Neurosci 29:14057–14065PubMedCrossRefGoogle Scholar
- 3.ASDA (2005) The International Classification of Sleep Disorders, 2nd edition. Diagnostic and coding manual. American Sleep Disorders Association, ChicagoGoogle Scholar
- 8.Ejskjaer N, Vestergaard ET, Hellstrom PM, Gormsen LC, Madsbad S, Madsen JL, Jensen TA, Pezzullo JC, Christiansen JS, Shaughnessy L, Kosutic G (2009) Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis. Aliment Pharmacol Ther 29:1179–1187PubMedCrossRefGoogle Scholar
- 19.Schenck CH, Bundlie S, Mahowald MW (2003) REM sleep behaviour disorder (RBD) delayed emergence of parkinsonism and/or dementia in 65% of older men initially diagnosed with idiopathic RBD, and an analysis of the maximum & minimum tonic and/or phasic electromyographic abnormalities found during REM sleep. Sleep 26:A316Google Scholar
- 22.Stiasny-Kolster K, Doerr Y, Moller JC, Hoffken H, Behr TM, Oertel WH, Mayer G (2005) Combination of ‘idiopathic’ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 128:126–137PubMedCrossRefGoogle Scholar
- 23.Unger MM, Hattemer K, Moller JC, Schmittinger K, Mankel K, Eggert K, Strauch K, Tebbe JJ, Keil B, Oertel WH, Heverhagen JT, Knake S (2010) Real-time visualization of altered gastric motility by magnetic resonance imaging in patients with Parkinson’s disease. Mov Disord 25:623–628PubMedGoogle Scholar