scholarly journals Enriched environmental conditions modify the gut microbiome composition and fecal markers of inflammation in Parkinson’s disease

2019 ◽  
Author(s):  
Yogesh Singh ◽  
Mohamed El Hadidi ◽  
Jakob Matthes ◽  
Zinah Wassouf ◽  
Julia M. Schulze-Hentrich ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transgenic Mice ◽  
Environmental Conditions ◽  
Gut Microbiome ◽  
Gut Bacteria ◽  
Dietary Factors ◽  
Enriched Environment ◽  
Wild Type ◽  
Markers Of Inflammation

AbstractBackgroundRecent findings suggest an implication of the gut microbiome in Parkinson’s disease patients. Parkinson’s disease onset and progression has also been linked with various environmental factors such as physical activity, exposure to pesticides, head injury, nicotine, and dietary factors.ObjectivesIn this study, we used a transgenic mouse model overexpressing the complete human SNCA genes modeling familial and sporadic forms of Parkinson’s disease to study whether environmental conditions such as standard versus enriched environment changes the gut microbiome and influences disease progression.MethodsWe performed 16S rRNA DNA sequencing on fecal samples for microbiome analysis and studied fecal inflammatory calprotectin from the colon of control and transgenic mice kept under standard environment and enriched environment conditions.ResultsThe overall composition of the gut microbiota was not changed in transgenic mice compared with wild-type in enriched environment, however, individual gut bacteria at genus level such as Lactobacillus sp. were significantly changed in transgenic mice. Furthermore, enriched environment significantly reduced colon fecal inflammatory calprotectin protein in wild-type and transgenic enriched environment conditions compared to standard environment.ConclusionOur data suggest that enriched social environment has a positive effect on the induction of SNCA mediated inflammation in the intestine by changing anti-inflammatory gut bacteria.

scholarly journals α-Synuclein impairs macroautophagy: implications for Parkinson’s disease

2010 ◽  
Vol 190 (6) ◽  
pp. 1023-1037 ◽  
Author(s):  
Ashley R. Winslow ◽  
Chien-Wen Chen ◽  
Silvia Corrochano ◽  
Abraham Acevedo-Arozena ◽  
David E. Gordon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transgenic Mice ◽  
Mammalian Cells ◽  
Gene Locus ◽  
Lewy Bodies ◽  
Wild Type

Parkinson’s disease (PD) is characterized pathologically by intraneuronal inclusions called Lewy bodies, largely comprised of α-synuclein. Multiplication of the α-synuclein gene locus increases α-synuclein expression and causes PD. Thus, overexpression of wild-type α-synuclein is toxic. In this study, we demonstrate that α-synuclein overexpression impairs macroautophagy in mammalian cells and in transgenic mice. Our data show that α-synuclein compromises autophagy via Rab1a inhibition and Rab1a overexpression rescues the autophagy defect caused by α-synuclein. Inhibition of autophagy by α-synuclein overexpression or Rab1a knockdown causes mislocalization of the autophagy protein, Atg9, and decreases omegasome formation. Rab1a, α-synuclein, and Atg9 all regulate formation of the omegasome, which marks autophagosome precursors.

scholarly journals Gut microbiome signatures of risk and prodromal markers of Parkinson's disease

2021 ◽  
Author(s):  
Sebastian Heinzel ◽  
Velma T. E. Aho ◽  
Ulrike Suenkel ◽  
Anna‐Katharina Thaler ◽  
Claudia Schulte ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome

scholarly journals Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Stefano Romano ◽  
George M. Savva ◽  
Janis R. Bedarf ◽  
Ian G. Charles ◽  
Falk Hildebrand ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Short Chain Fatty Acids ◽  
Inflammatory Status

AbstractThe gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts. We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients.

The impact of device-assisted therapies on the gut microbiome in Parkinson’s disease

2021 ◽  
Author(s):  
Michal Lubomski ◽  
Xiangnan Xu ◽  
Andrew J. Holmes ◽  
Jean Y. H. Yang ◽  
Carolyn M. Sue ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome ◽  
The Impact

scholarly journals α-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia: a prodromal Parkinson’s disease model

Brain ◽  
2019 ◽  
Vol 143 (1) ◽  
pp. 249-265 ◽  
Author(s):  
Tomoyuki Taguchi ◽  
Masashi Ikuno ◽  
Mari Hondo ◽  
Laxmi Kumar Parajuli ◽  
Katsutoshi Taguchi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transgenic Mice ◽  
Rem Sleep ◽  
Genome Wide Association Study ◽  
Artificial Chromosome ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Familial Parkinson’S Disease

Abstract Parkinson’s disease is one of the most common movement disorders and is characterized by dopaminergic cell loss and the accumulation of pathological α-synuclein, but its precise pathogenetic mechanisms remain elusive. To develop disease-modifying therapies for Parkinson’s disease, an animal model that recapitulates the pathology and symptoms of the disease, especially in the prodromal stage, is indispensable. As subjects with α-synuclein gene (SNCA) multiplication as well as point mutations develop familial Parkinson’s disease and a genome-wide association study in Parkinson’s disease has identified SNCA as a risk gene for Parkinson’s disease, the increased expression of α-synuclein is closely associated with the aetiology of Parkinson’s disease. In this study we generated bacterial artificial chromosome transgenic mice harbouring SNCA and its gene expression regulatory regions in order to maintain the native expression pattern of α-synuclein. Furthermore, to enhance the pathological properties of α-synuclein, we inserted into SNCA an A53T mutation, two single-nucleotide polymorphisms identified in a genome-wide association study in Parkinson’s disease and a Rep1 polymorphism, all of which are causal of familial Parkinson’s disease or increase the risk of sporadic Parkinson’s disease. These A53T SNCA bacterial artificial chromosome transgenic mice showed an expression pattern of human α-synuclein very similar to that of endogenous mouse α-synuclein. They expressed truncated, oligomeric and proteinase K-resistant phosphorylated forms of α-synuclein in the regions that are specifically affected in Parkinson’s disease and/or dementia with Lewy bodies, including the olfactory bulb, cerebral cortex, striatum and substantia nigra. Surprisingly, these mice exhibited rapid eye movement (REM) sleep without atonia, which is a key feature of REM sleep behaviour disorder, at as early as 5 months of age. Consistent with this observation, the REM sleep-regulating neuronal populations in the lower brainstem, including the sublaterodorsal tegmental nucleus, nuclei in the ventromedial medullary reticular formation and the pedunculopontine nuclei, expressed phosphorylated α-synuclein. In addition, they also showed hyposmia at 9 months of age, which is consistent with the significant accumulation of phosphorylated α-synuclein in the olfactory bulb. The dopaminergic neurons in the substantia nigra pars compacta degenerated, and their number was decreased in an age-dependent manner by up to 17.1% at 18 months of age compared to wild-type, although the mice did not show any related locomotor dysfunction. In conclusion, we created a novel mouse model of prodromal Parkinson’s disease that showed RBD-like behaviour and hyposmia without motor symptoms.

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