title: Upregulation of GPR109A in Parkinson's disease.
abstract: BACKGROUND
  Anecdotal animal and human studies have implicated the symptomatic and neuroprotective roles of niacin in Parkinson's disease (PD). Niacin has a high affinity for GPR109A, an anti-inflammatory receptor. Niacin is also thought to be involved in the regulation of circadian rhythm. Here we evaluated the relationships among the receptor, niacin levels and EEG night-sleep in individuals with PD.
  
  
  RESULTS
  GPR109A expression (blood and brain), niacin index (NAD-NADP ratio) and cytokine markers (blood) were analyzed. Measures of night-sleep function (EEG) and perceived sleep quality (questionnaire) were assessed. We observed significant up-regulation of GPR109A expression in the blood as well as in the substantia nigra (SN) in the PD group compared to age-matched controls. Confocal microscopy demonstrated co-localization of GPR109A staining with microglia in PD SN. Pro and anti-inflammatory cytokines did not show significant differences between the groups; however IL1-β, IL-4 and IL-7 showed an upward trend in PD. Time to sleep (sleep latency), EEG REM and sleep efficiency were different between PD and age-matched controls. Niacin levels were lower in PD and were associated with increased frequency of experiencing body pain and decreased duration of deep sleep.
  
  
  CONCLUSIONS
  The findings of associations among the GPR109A receptor, niacin levels and night-sleep function in individuals with PD are novel. Further studies are needed to understand the pathophysiological mechanisms of action of niacin, GPR109A expression and their associations with night-sleep function. It would be also crucial to study GPR109A expression in neurons, astrocytes, and microglia in PD. A clinical trial to determine the symptomatic and/or neuroprotective effect of niacin supplementation is warranted.
authors.affiliation: Department of Physical Therapy, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Chandramohan
authors.initials: C
authors.lastname: Wakade
authors.affiliation: Department of Physical Therapy, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Raymond
authors.initials: R
authors.lastname: Chong
authors.affiliation: Department of Physical Therapy, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Bradley
authors.affiliation: Department of Pharmacology & Toxicology and Neurology, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Bobby
authors.initials: B
authors.lastname: Thomas
authors.affiliation: Department of Neurology, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Morgan
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012890:Sleep; D013378:Substantia Nigra / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C530636:HCAR2 protein, human; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D009525:Niacin