Cognition and serotonin in Parkinson's disease

Frouni, Imane; Kwan, Cynthia; Belliveau, Sébastien

doi:10.1016/bs.pbr.2022.01.013

Cited by 12 publications

(4 citation statements)

References 224 publications

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“…The highest concentration of serotonin is in the gut. Serotonin abnormalities have been detected at various stages of PD, from before the development of motor symptoms, making it a potential early diagnostic marker 47 , to late stages of PD where it may be a risk factor for cognitive decline 48 . It was shown in mice that spore forming bacteria induce production of serotonin in host colonic cells 49 .…”

Section: Functional Inferencementioning

confidence: 99%

Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

et al. 2022

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Parkinson’s disease (PD) may start in the gut and spread to the brain. To investigate the role of gut microbiome, we conducted a large-scale study, at high taxonomic resolution, using uniform standardized methods from start to end. We enrolled 490 PD and 234 control individuals, conducted deep shotgun sequencing of fecal DNA, followed by metagenome-wide association studies requiring significance by two methods (ANCOM-BC and MaAsLin2) to declare disease association, network analysis to identify polymicrobial clusters, and functional profiling. Here we show that over 30% of species, genes and pathways tested have altered abundances in PD, depicting a widespread dysbiosis. PD-associated species form polymicrobial clusters that grow or shrink together, and some compete. PD microbiome is disease permissive, evidenced by overabundance of pathogens and immunogenic components, dysregulated neuroactive signaling, preponderance of molecules that induce alpha-synuclein pathology, and over-production of toxicants; with the reduction in anti-inflammatory and neuroprotective factors limiting the capacity to recover. We validate, in human PD, findings that were observed in experimental models; reconcile and resolve human PD microbiome literature; and provide a broad foundation with a wealth of concrete testable hypotheses to discern the role of the gut microbiome in PD.

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Section: Functional Inferencementioning

confidence: 99%

Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

et al. 2022

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“…Reduced serotonin synthesis in PD alongside dopamine reflects the degeneration of both neurotransmitter systems. Serotonergic impairment in PD is well-known but poorly understood 24 . We show that the decrease in serotonin is apparent regardless of cognition status but we found a significant association with senile plaque formation.…”

Section: Discussionmentioning

confidence: 99%

Targeted metabolomic analysis in Parkinson’s disease brain frontal cortex and putamen with relation to cognitive impairment

Kalecky

2023

npj Parkinsons Dis.

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We performed liquid chromatography tandem mass spectrometry analysis with the targeted metabolomic kit Biocrates MxP Quant 500, in human brain cortex (Brodmann area 9) and putamen, to reveal metabolic changes characteristic of Parkinson’s disease (PD) and PD-related cognitive decline. This case-control study involved 101 subjects (33 PD without dementia, 32 PD with dementia (cortex only), 36 controls). We found changes associated with PD, cognitive status, levodopa levels, and disease progression. The affected pathways include neurotransmitters, bile acids, homocysteine metabolism, amino acids, TCA cycle, polyamines, β-alanine metabolism, fatty acids, acylcarnitines, ceramides, phosphatidylcholines, and several microbiome-derived metabolites. Previously reported levodopa-related homocysteine accumulation in cortex still best explains the dementia status in PD, which can be modified by dietary supplementation. Further investigation is needed to reveal the exact mechanisms behind this pathological change.

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“…The highest concentration of serotonin is in the gut. Serotonin abnormalities have been detected at various stages of PD, from before the development of motor symptoms, making it a potential early diagnostic marker 49 , to late stages of PD where it may be a risk factor for cognitive decline 50 . It was shown in mice that spore forming bacteria induce production of serotonin in host colonic cells, which stimulates myenteric neurons and gut motility 51 .…”

Section: Gaba and Glutamatementioning

confidence: 99%

Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

Wallen

Demirkan

Twa

et al. 2022

Preprint

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Parkinson's disease (PD) may start in the gut and spread to the brain. To investigate the role of gut microbiome, we enrolled 490 PD and 234 control individuals, conducted deep shotgun sequencing of fecal DNA, followed by metagenome-wide association studies requiring significance by two methods (ANCOM-BC and MaAsLin2) to declare disease association. Thirty-percent of species and pathways tested had altered abundances in PD, depicting a widespread dysbiosis. Network analysis showed PD-associated species form polymicrobial clusters that grow or shrink together, and some compete. Metagenomic profile of PD indicates a disease permissive microbiome, evidenced by overabundance of pathogens and immunogenic components, dysregulated neuroactive signaling, preponderance of molecules that induce alpha-synuclein pathology, and over-production of toxicants; with the reduction in anti-inflammatory and neuroprotective factors limiting the capacity to recover. These data provide a broad foundation with a wealth of concrete testable hypotheses to discern the role of the gut microbiome in PD.

show abstract

Cognition and serotonin in Parkinson's disease

Cited by 12 publications

References 224 publications

Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

Targeted metabolomic analysis in Parkinson’s disease brain frontal cortex and putamen with relation to cognitive impairment

Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

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