Gastrointestinal Dysfunction and Neuropathologic Correlations in Parkinson Disease

Mrabet, S.; Ali, Nadia; Achouri, Afef; Dabbeche, R.; Najjar, Taoufik; Haouet, S; Belal, Samir

doi:10.1097/mcg.0000000000000606

Cited by 25 publications

(25 citation statements)

References 17 publications

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“…[ 7 , 8 ] Increasing evidence indicates that PD is also involved in the dopamine system of other organs (such as pathways in the mesolimbic system, mesocortical pathways, and dopaminergic neurons in the gastrointestinal tract), the serotonergic system, cholinergic system, noradrenergic system, and peptide neurotransmitter systems (such as enkephalin system and dynorphin system), likely underlying a series of non-motor PD symptoms. [ 9 – 12 ]…”

Section: Introductionmentioning

confidence: 99%

Gastrointestinal nervous system α-synuclein as a potential biomarker of Parkinson disease

Yan

Chen

et al. 2018

Medicine

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Lewy bodies (LB) play an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons in Parkinson disease (PD). Alpha-synuclein (α-synuclein) is the major component of Lewy bodies and is a potential target for Parkinson's disease (PD) therapies. α-synuclein can be detected in the gastrointestinal (GI) nervous system, but whether there is any association between altered α-synuclein expression in the GI nervous system and the onset of PD is not known. The answer to this question presents the opportunity for a promising biomarker in the pre-clinical diagnosis of PD. As such, this study aimed to measure the α-synuclein level in the GI nervous system of Parkinson's disease patients.The protein levels of α-synuclein in the GI nervous system of 31 PD patients (PD group) and 32 patients without PD or Parkinsonism-plus syndrome (control group) were evaluated via immunohistochemical staining. The χ2 test was performed to evaluate the differences between the PD group and control group. In addition to the distribution of α-synuclein positive protein, regional distribution of the protein in the stomach was also evaluated across groups.Alpha synuclein overexpression was found in the GI nervous tissue of PD patients. The PD group included 17 positive results and 14 negative results. The control group exhibited 7 positive results and 24 negative results. The χ2 test showed that χ2 = 7.255, P = .01. The distribution of these positive cases in the gastrointestinal system, the χ2 test showed that P = .949. The 21 stomach tissues had 7 α-synuclein positive protein tissues, while the body of stomach (4 α-synuclein positive protein) was higher than in other regions.Aberrant expression of α-synuclein was detected in the GI tissues of PD patients, though the distribution of α-synuclein in the gastrointestinal tract had no specificity. Gastrointestinal mucous biopsy could be regarded as a potential opportunity for the early-stage diagnostic exploration of PD, through the detection of α-synuclein inclusions.

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Section: Introductionmentioning

confidence: 99%

Gastrointestinal nervous system α-synuclein as a potential biomarker of Parkinson disease

Yan

Chen

et al. 2018

Medicine

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“…Lewy type pathology also emerges in the peripheral autonomous nervous system (PANS) [1, 2] and is known to occur in early, prodromal stages. Abnormal aggregates of synuclein are not uncommon in the enteric neurons of PD patients and the evidence of a prion-like behavior of synuclein [3] has focused the attention on the assessment of the enteric nervous system in PD in line with the hypothesis that the gut is the initial site of synuclein aggregation [4–6]. Since abnormal aggregates of synuclein are found in the enteric neurons in PD, a colonic biopsy could provide access to a unique tissue to study pathophysiological aspects of the disease [4–6].…”

Section: Introductionmentioning

confidence: 99%

“…Although the main molecular features remaining at the core of PD etiopathogenesis are (i) mitochondrial alterations, (ii) oxidative damage, and (iii) the mishandling degradation of proteins [21–23], only unfolded proteins have been assessed at PANS level [4–6] from subjects suffering from idiopathic REM sleep behavior disorder (iRBD), a parasomnia characterized by dream enactment behavior and atonia during REM sleep. iRBD patients are considered to suffer prodromal synucleinopathies since up to 80% of these patients develop a neurodegenerative disease, associated with Lewy body pathology [24–26].…”

Section: Introductionmentioning

confidence: 99%

Colonic Oxidative and Mitochondrial Function in Parkinson’s Disease and Idiopathic REM Sleep Behavior Disorder

Morén

González‐Casacuberta

Navarro‐Otano

et al. 2017

Parkinson's Disease

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Objective To determine potential mitochondrial and oxidative alterations in colon biopsies from idiopathic REM sleep behavior disorder (iRBD) and Parkinson's disease (PD) subjects. Methods Colonic biopsies from 7 iRBD subjects, 9 subjects with clinically diagnosed PD, and 9 healthy controls were homogenized in 5% w/v mannitol. Citrate synthase (CS) and complex I (CI) were analyzed spectrophotometrically. Oxidative damage was assessed either by lipid peroxidation, through malondialdehyde and hydroxyalkenal content by spectrophotometry, or through antioxidant enzyme levels of superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (Gpx1), and catalase (CAT) by western blot. The presence of mitochondrial DNA (mtDNA) deletions was assessed by long PCR and electrophoresis. Results Nonsignificant trends to CI decrease in both iRBD (45.69 ± 18.15; 23% decrease) and PD patients (37.57 ± 12.41; 37% decrease) were found compared to controls (59.51 ± 12.52, p: NS). Lipid peroxidation was maintained among groups (iRBD: 27.46 ± 3.04, PD: 37.2 ± 3.92, and controls: 31.71 ± 3.94; p: NS). Antioxidant enzymes SOD2 (iRBD: 2.30 ± 0.92, PD: 1.48 ± 0.39, and controls: 1.09 ± 0.318) and Gpx1 (iRBD 0.29 ± 0.12, PD: 0.56 ± 0.33, and controls: 0.38 ± 0.16) did not show significant differences between groups. CAT was only detected in 2 controls and 1 iRBD subject. One iRBD patient presented a single mtDNA deletion.

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“…A53T alpha-synuclein mice developed age-related declines in stool frequency and gastric emptying consistent with those seen in human PD (Noorian et al, 2012 ). One clinical study reported that synucleinopathy in the enteric nervous system was significantly correlated with frequency and severity of GI dysfunction motor disability in PD patients (Mrabet et al, 2016 ), supporting the relationship between alpha-synuclein deposition in the enteric nervous system and GI dysfunction. In the present study, the GI dysfunctions are taken in account considering that the dietary iron supplements might induce and interact synucleinopathy on this primary site.…”

Section: Discussionmentioning

confidence: 91%

High Dietary Iron Supplement Induces the Nigrostriatal Dopaminergic Neurons Lesion in Transgenic Mice Expressing Mutant A53T Human Alpha-Synuclein

Jia

Song

Wang

et al. 2018

Front. Aging Neurosci.

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Both alpha-synuclein aggregation and iron deposits are neuropathological hallmarks of Parkinson’s disease (PD). We are particularly interested in whether iron could synergize with alpha-synuclein pathology in vivo, especially in the nigrostriatal system. In the present study, we reported transgenic mice with overexpressing human A53T alpha-synuclein, as well as WT mice with high dietary iron displayed hyperactive motor coordination and impaired colonic motility, compared with those with basal dietary iron. Only A53T mice, but not WT mice with high dietary iron exhibited nigral dopaminergic neuronal loss, lower levels of tyrosine hydroxylase (TH) in the substantia nigra (SN) and decreased dopamine contents in the striatum. Although there was no obvious elevation of iron contents in the SN in WT mice with high dietary iron, we observed iron contents in the SN were especially higher than the other brain regions in 12-month aged mice with either high or basal dietary iron. These results suggested high dietary iron supplement could induce nigral dopaminergic neurons lesion in A53T mice, which might be due to the vulnerability of SN to accumulate iron.

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Gastrointestinal Dysfunction and Neuropathologic Correlations in Parkinson Disease

Cited by 25 publications

References 17 publications

Gastrointestinal nervous system α-synuclein as a potential biomarker of Parkinson disease

Gastrointestinal nervous system α-synuclein as a potential biomarker of Parkinson disease

Colonic Oxidative and Mitochondrial Function in Parkinson’s Disease and Idiopathic REM Sleep Behavior Disorder

High Dietary Iron Supplement Induces the Nigrostriatal Dopaminergic Neurons Lesion in Transgenic Mice Expressing Mutant A53T Human Alpha-Synuclein

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