Epigenetic contributions to hemisphere asymmetry in healthy brain, aging, and Parkinson’s disease

Li, Peipei; Ensink, Elizabeth; Lang, Sean; Marshall, Lee; Schilthuis, Meghan; Lamp, Jared; Vega, Irving E.; Labrie, Viviane

doi:10.1101/794255

Cited by 3 publications

(3 citation statements)

References 99 publications

(107 reference statements)

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“…This study also identified leukocyte genes whose methylation correlated with fecal butyrate levels in patients. To connect these butyrate-associated changes in peripheral methylation to changes within the brain, the researchers compared the identified leukocyte genes to previous work that identified genes with altered methylation in prefrontal cortical neurons (Li et al, 2020). They found significant overlap and correlated likelihood of methylation in Parkinson's disease patients for the leukocyte and neuronal genes, suggesting the potential for decreased butyrate levels to contribute to neurological changes through effects on brain DNA methylation (Xie et al, 2022).…”

Section: Gut-brain Axismentioning

confidence: 99%

Microbiota and nutrition as risk and resiliency factors following prenatal alcohol exposure

Upreti,

Rouzer,

Bowring

et al. 2023

Front. Neurosci.

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Alcohol exposure in adulthood can result in inflammation, malnutrition, and altered gastroenteric microbiota, which may disrupt efficient nutrient extraction. Clinical and preclinical studies have documented convincingly that prenatal alcohol exposure (PAE) also results in persistent inflammation and nutrition deficiencies, though research on the impact of PAE on the enteric microbiota is in its infancy. Importantly, other neurodevelopmental disorders, including autism spectrum and attention deficit/hyperactivity disorders, have been linked to gut microbiota dysbiosis. The combined evidence from alcohol exposure in adulthood and from other neurodevelopmental disorders supports the hypothesis that gut microbiota dysbiosis is likely an etiological feature that contributes to negative developmental, including neurodevelopmental, consequences of PAE and results in fetal alcohol spectrum disorders. Here, we highlight published data that support a role for gut microbiota in healthy development and explore the implication of these studies for the role of altered microbiota in the lifelong health consequences of PAE.

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Section: Gut-brain Axismentioning

confidence: 99%

Microbiota and nutrition as risk and resiliency factors following prenatal alcohol exposure

Upreti,

Rouzer,

Bowring

et al. 2023

Front. Neurosci.

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“…Although epigenome-wide association studies (EWAS) have demonstrated altered DNAm patterns in individuals with PD in comparison to healthy subjects, the majority of findings were not replicable between studies (Masliah et al, 2013;Moore et al, 2014;Henderson-Smith et al, 2019;Li et al, 2020;Marshall et al, 2020;Vallerga et al, 2020;Henderson et al, 2021;Kia et al, 2021;Nabais et al, 2021;Kaut et al, 2022) (Supplementary Tables S1, S2). However, PD-related DNAm changes in particular genes, such as CYP2E1, have been reported in brain and blood across multiple studies (Kaut et al, 2012;Henderson-Smith et al, 2019;Kaut et al, 2022).…”

Section: Introductionmentioning

confidence: 97%

DNA methylation as a mediator of genetic and environmental influences on Parkinson’s disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenome

Schaffner

Kobor

2022

Front. Genet.

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Parkinson’s disease (PD) is a neurodegenerative disorder with a complex etiology and increasing prevalence worldwide. As PD is influenced by a combination of genetic and environment/lifestyle factors in approximately 90% of cases, there is increasing interest in identification of the interindividual mechanisms underlying the development of PD as well as actionable lifestyle factors that can influence risk. This narrative review presents an outline of the genetic and environmental factors contributing to PD risk and explores the possible roles of cytosine methylation and hydroxymethylation in the etiology and/or as early-stage biomarkers of PD, with an emphasis on epigenome-wide association studies (EWAS) of PD conducted over the past decade. Specifically, we focused on variants in the SNCA gene, exposure to pesticides, and physical activity as key contributors to PD risk. Current research indicates that these factors individually impact the epigenome, particularly at the level of CpG methylation. There is also emerging evidence for interaction effects between genetic and environmental contributions to PD risk, possibly acting across multiple omics layers. We speculated that this may be one reason for the poor replicability of the results of EWAS for PD reported to date. Our goal is to provide direction for future epigenetics studies of PD to build upon existing foundations and leverage large datasets, new technologies, and relevant statistical approaches to further elucidate the etiology of this disease.

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“…Abnormal cerebral specialization in PD has been shown in studies from molecular biology and neuroimaging. For example, the asymmetry of DNA methylation in prefrontal cortex neurons is greater in PD patients than healthy controls, and has been linked to the disease course (Li et al, 2020). Diffusion tensor imaging studies also indicate abnormal structural asymmetry of the bilateral substantia nigra in PD patients (Prakash et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Brain functional specialization and cooperation in Parkinson’s disease

Sun

Gao

Hua

et al. 2021

Brain Imaging and Behavior

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Background: Cerebral specialization and inter-hemispheric cooperation are two of the most prominent functional architectures of the human brain. Their dysfunctions may be related to pathophysiological changes in patients with Parkinson's disease (PD), who are characterized by unbalanced onset and progression of motor symptoms.Objective: This study aimed to characterize the two intrinsic architectures of hemispheric functions in PD using resting-state functional magnetic resonance imaging.Methods: Seventy idiopathic PD patients and 70 age-, sex-, and education-matched healthy subjects were recruited. All participants underwent magnetic resonance image scanning and clinical evaluations. The cerebral specialization (Autonomy index, AI) and inter-hemispheric cooperation (Connectivity between Functionally Homotopic voxels, CFH) were calculated and compared between groups.Results: Compared with healthy controls, PD patients showed stronger AI in the left angular gyrus. Speci cally, this difference in specialization resulted from increased functional connectivity (FC) of the ipsilateral areas (e.g., the left prefrontal area), and decreased FC in the contralateral area (e.g., the right supramarginal gyrus). Imaging-cognitive correlation analysis indicated that these connectivity were positively related to the score of Montreal Cognitive Assessment in PD patients. CFH between the bilateral sensorimotor regions was signi cantly decreased in PD patients compared with controls. No signi cant correlation between CFH and cognitive scores was found in PD patients.Conclusions: This study illustrated a strong leftward specialization but weak inter-hemispheric coordination in PD patients. It provided new insights to further clarify the pathological mechanism of PD.

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Epigenetic contributions to hemisphere asymmetry in healthy brain, aging, and Parkinson’s disease

Cited by 3 publications

References 99 publications

Microbiota and nutrition as risk and resiliency factors following prenatal alcohol exposure

Microbiota and nutrition as risk and resiliency factors following prenatal alcohol exposure

DNA methylation as a mediator of genetic and environmental influences on Parkinson’s disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenome

Brain functional specialization and cooperation in Parkinson’s disease

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