title: Distinct pattern of enteric phospho-alpha-synuclein aggregates and gene expression profiles in patients with Parkinson's disease.
abstract: Phosphorylated alpha-synuclein (p-α-syn) containing Lewy bodies (LBs) and Lewy neurites (LNs) are neuropathological hallmarks of Parkinson's disease (PD) in the central nervous system (CNS). Since they have been also demonstrated in the enteric nervous system (ENS) of PD patients, the aim of the study was to analyze enteric p-α-syn positive aggregates and intestinal gene expression. Submucosal rectal biopsies were obtained from patients with PD and controls and processed for dual-label-immunohistochemistry for p-α-syn and PGP 9.5. p-α-syn positive aggregates in nerve fibers and neuronal somata were subjected to a morphometric analysis. mRNA expression of α-syn and dopaminergic, serotonergic, VIP (vaso intestinal peptide) ergic, cholinergic, muscarinergic neurotransmitter systems were investigated using qPCR. Frequency of p-α-syn positive nerve fibers was comparable between PD and controls. Although neuronal p-α-syn positive aggregates were detectable in both groups, total number and area of p-α-syn positive aggregates were increased in PD patients as was the number of small and large sized aggregates. Increased expression of dopamine receptor D1, VIP and serotonin receptor 3A was observed in PD patients, while serotonin receptor 4 and muscarinic receptor 3 (M3R) were downregulated. M3R expression correlated negative with the number of small sized p-α-syn positive aggregates. The findings strengthen the hypothesis that the CNS pathology of increased p-α-syn in PD also applies to the ENS, if elaborated morphometry is applied and give further insights in altered intestinal gene expression in PD. Although the mere presence of p-α-syn positive aggregates in the ENS should not be regarded as a criterion for PD diagnosis, elaborated morphometric analysis of p-α-syn positive aggregates in gastrointestinal biopsies could serve as a suitable tool for in-vivo diagnosis of PD.
authors.affiliation: Institute of Anatomy, Kiel University, Kiel, Germany. m.barrenschee@anat.uni-kiel.de.
authors.forename: Martina
authors.initials: M
authors.lastname: Barrenschee
authors.affiliation: Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Zorenkov
authors.affiliation: Institute of Anatomy, Kiel University, Kiel, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Böttner
authors.affiliation: Institute of Anatomy, Kiel University, Kiel, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Lange
authors.affiliation: Institute of Anatomy, Kiel University, Kiel, Germany.
authors.forename: François
authors.initials: F
authors.lastname: Cossais
authors.affiliation: Institute of Anatomy, Kiel University, Kiel, Germany.
authors.forename: Amelie Bernadette
authors.initials: AB
authors.lastname: Scharf
authors.affiliation: Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Deuschl
authors.affiliation: Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Schneider
authors.affiliation: Experimental Endoscopy, Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Ellrichmann
authors.affiliation: Experimental Endoscopy, Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Fritscher-Ravens
authors.affiliation: Institute of Anatomy, Kiel University, Kiel, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Wedel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003113:Colonoscopy; D017615:Enteric Nervous System / Q000378:metabolism* / Q000473:pathology*; D005725:Ganglia, Autonomic / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012007:Rectum / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C497604:SNCA protein, human; D051844:alpha-Synuclein
keywords: Enteric nervous system; Gastrointestinal biopsies; Gene expression; Parkinson’s disease; p-α-synuclein