Bacterial Butyrate in Parkinson's Disease Is Linked to Epigenetic Changes and Depressive Symptoms

Background The gut microbiome and its metabolites can impact brain health and are altered in Parkinson's disease (PD) patients. It has been recently demonstrated that PD patients have reduced fecal levels of the potent epigenetic modulator butyrate and its bacterial producers. Objectives Here, we investigate whether the changes in the gut microbiome and associated metabolites are related to PD symptoms and epigenetic markers in leucocytes and neurons. Methods Stool, whole blood samples, and clinical data were collected from 55 PD patients and 55 controls. We performed DNA methylation analysis on whole blood samples and analyzed the results in relation to fecal short-chain fatty acid concentrations and microbiota composition. In another cohort, prefrontal cortex neurons were isolated from control and PD brains. We identified genome-wide DNA methylation by targeted bisulfite sequencing. Results We show that lower fecal butyrate and reduced counts of genera Roseburia, Romboutsia, and Prevotella are related to depressive symptoms in PD patients. Genes containing butyrate-associated methylation sites include PD risk genes and significantly overlap with sites epigenetically altered in PD blood leucocytes, predominantly neutrophils, and in brain neurons, relative to controls. Moreover, butyrate-associated methylated-DNA regions in PD overlap with those altered in gastrointestinal (GI), autoimmune, and psychiatric diseases. Conclusions Decreased levels of bacterially produced butyrate are related to epigenetic changes in leucocytes and neurons from PD patients and to the severity of their depressive symptoms. PD shares common butyrate-dependent epigenetic changes with certain GI and psychiatric disorders, which could be relevant for their epidemiological relation. (c) 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder SocietyPeer reviewe

Киберпространство и виртуальная реальность: попытка историко-философского анализа

Материалы IV Республик. науч. конф. студентов, магистрантов и аспирантов, Гомель, 12 мая 2011 г

The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid β fibril formation

Point mutations in the amyloid precursor protein gene (APP) cause familial Alzheimer's disease (AD) by increasing generation or altering conformation of amyloid beta (A beta). Here, we describe the Uppsala APP mutation (Delta 690-695), the first reported deletion causing autosomal dominant AD. Affected individuals have an age at symptom onset in their early forties and suffer from a rapidly progressing disease course. Symptoms and biomarkers are typical of AD, with the exception of normal cerebrospinal fluid (CSF) A beta 42 and only slightly pathological amyloid-positron emission tomography signals. Mass spectrometry and Western blot analyses of patient CSF and media from experimental cell cultures indicate that the Uppsala APP mutation alters APP processing by increasing beta-secretase cleavage and affecting alpha-secretase cleavage. Furthermore, in vitro aggregation studies and analyses of patient brain tissue samples indicate that the longer form of mutated A beta, A beta Upp1-42(Delta 19-24), accelerates the formation of fibrils with unique polymorphs and their deposition into amyloid plaques in the affected brain

Association study of cholesterol-related genes in Alzheimer's disease

Alzheimer's disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have screened genes that map to chromosomal regions with high logarithm of the odds scores for AD in full genome scans and are related to cholesterol metabolism. In a European screening sample of 115 sporadic AD patients and 191 healthy control subjects, we analyzed single nucleotide polymorphisms in 28 cholesterol-related genes for association with AD. The genes HMGCS2, FDPS, RAFTLIN, ACAD8, NPC2, and ABCG1 were associated with AD at a significance level of P ≤ 0.05 in this sample. Replication trials in five independent European samples detected associations of variants within HMGCS2, FDPS, NPC2, or ABCG1 with AD in some samples (P = 0.05 to P = 0.005). We did not identify a marker that was significantly associated with AD in the pooled sample (n = 2864). Stratification of this sample revealed an APOE-dependent association of HMGCS2 with AD (P = 0.004). We conclude that genetic variants investigated in this study may be associated with a moderate modification of the risk for AD in some sample

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Institute of Freshwater Research. Drottningholm : Report No 37

InnehållZur Systematik der Orthocladiinae (Dipt. Chironomidae)Die bodenfaimistischen Seetypen und ihre Anwendbarkeit auf die Südhalbkugel. Zugleich eine Theorie der produktionsbiologischen Bedeutung der glazialen Erosion</p

Chironomids and Other Bottom Animals of the Oligotrophic Lakes in South Sweden : A Contribution to the Knowledge of the Bottomfaunistical Characteristics of the Swedish Oligotrophic Lakes

Problems. Methods. Material. There are more than 85000 lakes in Sweden, the majority of which belong to the oligotrophic type sensu Naumann, and which present an inexhaustible field for investigation. In view of the varied and complicated nature of the problems and the young age of limnological science it is natural that the knowledge of these lakes in spite of the efforts of many investigators should still be fragmentary. This holds good also of the bottom fauna which in many respects is so important. When, in 1941—1942, I was working on a quantitative material of bottom animals from oligotrophic lakes in Jämtland, North Sweden, this lack of data was strongly felt. There was no solid holding-ground for a comparison with other lakes in Sweden, and many factors indicated that the production of the bottom animals in oligotrophic lakes in Sweden was considerably underestimated, probably because of the methods not being quite satisfactory. Particularly conflicting results had been reached by previous investigators as regards the influence of the humic standard on the bottom fauna, which is a vital problem concerning the Swedish lakes. As regards the chironomids constituting, as is well known, the most important group among the bottom animals in the Swedish lakes, our almost complete lack of knowledge was most deeply felt. It was clear that a real understanding of the relationship between the different laketypes and the profundal fauna could only be obtained by determining the species represented by the chironomid larvae. The very fact that certain lakes in Jämtland that Naumann would undoubtedly have characterized as oligotrophic had a chironomid fauna, which according to the valid typology of the lakes based on the bottom faunistical conditions must be regarded as belonging to the mesotrophic type, was in itself an inducement enough for a closer study of chironomids and their dependence on environmental factors. Thus important problems were waiting for a solution. To contribute to this I started studies of the bottom fauna in 1942 with a particular regard to the chironomids in the Aneboda-Växjö district in the central part of the South-Swedish highland. These studies were concluded in the autumn of 1948

Institute of Freshwater Research. Drottningholm : Report No 37

InnehållZur Systematik der Orthocladiinae (Dipt. Chironomidae)Die bodenfaimistischen Seetypen und ihre Anwendbarkeit auf die Südhalbkugel. Zugleich eine Theorie der produktionsbiologischen Bedeutung der glazialen Erosion</p