Polymorphisms in the SNCA Gene: Association with the Risk of Development of the Sporadic Form of Parkinson’s Disease and the Level of SNCA Gene Expression in Peripheral Blood of Patients from Russia

Parkinson’s disease (PD) is one of the most common human neurodegenerative disorders caused by the loss of dopaminergic neurons in the brain. The α-synuclein (SNCA) gene is one of the most studied genes involved in the pathogenesis of PD. In our study, we conducted a genetic analysis of promoter and intron single-nucleotide polymorphisms (SNPs) in the SNCA gene. We also analyzed the association of genotypes of these SNPs with expression levels of SNCA mRNA. One of four SNPs in the SNCA gene, and the rs2736990 polymorphism, associates with the risk of the sporadic form of PD in Russian population. The risk of PD was increased almost twofold in carriers of allele C (odds ratios = 1.9, 95% confidence interval: 1.2-2.91, p = 0.003). However, no association was found between any of the genotypes of SNPs tested (rs2583988, rs2619363, rs2619364 and rs2736990) and alterations in SNCA levels. Our findings support the hypothesis that the rs2736990 polymorphism is associated with PD. SNPs rs2583988, rs2619363 and rs2619364 in the promoter region of the SNCA gene themselves do not significantly influence the expression of SNCA. Most likely, SNCA gene expression is a very complex process that is affected by different genetic and epigenetic factors.

Analysis of known point mutations and SNPs in genes responsible for monogenic Parkinson’s disease in Russian patients

Background: Parkinson’s disease (PD) is caused by complex interactions between genetic and environmental factors. Mendelian forms of PD rarely occur in practice, but respective genes may play some role in pathogenesis of a common sporadic form of the disease. Methods: We analyzed most frequent known point mutations (PMs) and single-nucleotide polymorphisms (SNPs) in genes responsible for monogenic PD in 408 Russian patients, using arrayed primer extension (APEX), real-time PCR, and restriction fragment length polymorphism analysis. Results: We detected only three heterozygous PMs in the PARK2 gene in three non-related patients with early-onset sporadic PD. No association between PD and the studied SNPs was identified. Conclusion: The examined PMs and SNPs in genes responsible for monogenic PD do not contribute significantly to the development of sporadic PD in Russia.

Transcriptome profiling of 6-OHDA model of Parkinson’s disease

Analysis of monogenic forms and candidate genes of Parkinson’s disease (PD) does not allow to describe completely the contribution of genetic factors to the etiopathogenesis of the disorder. An approach associated with an analysis of changes in a transcriptome pattern during the development of the disease in model objects can be used to identify new candidate genes that are involved in the pathogenesis of PD. In this work, we performed a transcriptome analysis of a PD model, created via stereotaxic unilateral introduction of the 6-hydroxidopamine (6-OHDA) into the substantia nigra pars compacta (SNpc) of a rat brain, to identify new candidate genes for PD. We studied transcriptome alterations in the substantia nigra of the rat brains 2 weeks after toxin administration, when the rats developed the Parkinson-like phenotype, and 4 weeks after toxin administration, when maximal changes in the behavior of animals were observed. The transcriptome analysis of the substantia nigra of the rat brains at the first time point (2 weeks) revealed changes in expression of genes that were clustered with high significance (p < 0.01, modified Fisher extract p value) into three metabolic pathways according to protein participation: modification of the extracellular matrix, signal transduction (including genes encoding signal peptides), and inflammation processes. This likely indicates that, during this time nonspecific effects associated with the response to surgery took place in the substantia nigra of the rats. Concomitantly, the situation changed dramatically and a response associated with damage to the nervous tissue was observed 4 weeks after neurotoxin administration. As a result, we identified five metabolic pathways containing predominantly genes, that encode protein products that are involved in the processes of neuron projection, normal functioning of the soma and dendrites of neurons, synaptic transmission, and transmission of nerve impulses (p < 0.01, modified Fisher extract p value).

Believing processes during the COVID-19 pandemic in individuals with bipolar disorder:An exploratory study

BACKGROUND Believing or“credition”refers to psychological processes that integrate the cognitions and emotions that influence our behavior.In the credition model by Angel and Seitz,four parameters are postulated:proposition,certainty,emotion and mightiness.It is assumed that believing processes are influenced by both the individual as well as socio-cultural factors and external circumstances.External or environmental circumstances can include threatening situations such as the ongoing pandemic.It has been hypothesized that believing processes related to the pandemic differ between individuals with bipolar disorder(BD)and healthy controls(HC).AIM To investigate credition in individuals with BD during the coronavirus disease 2019(COVID-19)pandemic.METHODS Psychiatrically stable individuals with BD(n=52)and age-and sex matched HC(n=52)participated in an online survey during the first lockdown of the COVID-19 pandemic.The survey took place between April 9^(th) and June 4^(th),2020,in Austria.Participants completed the Brief Symptom Inventory-18,the Beck Depression Inventory-Ⅱ,the Altman Self-Rating Mania Scale,the Pittsburgh Sleep Quality Index and a dedicated Believing Questionnaire assessing four parameters of credition(proposition,certainty,emotion and mightiness).The MAXQDA software was used to analyze the qualitative data.Statistical analyses included analyses of variance,a multivariate analysis of variance and a multivariate analysis of co-variance.RESULTS Individuals with BD reported significantly more negative propositions[F(1,102)=8.89,P=0.004,η2 p=0.08]and negative emotions[Welch´s F(1,82.46)=18.23,P<0.001,η2 p=0.18],while HC showed significantly more positive propositions[F(1,102)=7.78,P=0.006,η2 p=0.07]and emotions[F(1,102)=14.31,P<0.001,η2 p=0.12].In addition,individuals with BD showed a higher incongruence between their propositions and their emotions[F(1,102)=9.42,P=0.003,η2 p=0.08]and showed strong correlations between the parameters of the Believing Questionnaire and their psychiatric symptoms(r=0.51-0.77,all P<0.001).Positive as well as negative emotions and propositions were associated with scores measuring symptoms of depression,anxiety and sleep quality.CONCLUSION Believing parameters were associated with psychiatric symptoms in BD during the pandemic.Findings broaden knowledge about the susceptibility of believing processes for ambient challenges in individuals with BD.

轻偏瘫复发患者病觉缺失的诊断及发病率

Background: In previous studies, the incidence of anosognosia for hemiparesis has varied between 17%and 58%in samples of brain damaged patients with hemipar esis. Objective: To determine whether this wide variation might be explained by the different criteria used for diagnosing anosognosia. Methods:128 acute stroke patients with hemiparesis or hemiplegia were tested for anosognosia for hemipar esis using the anosognosia scale of Bisiach et al. Results: 94%of the patients who were rated as having “mild anosognosia"that is, they did not acknowledge th eir hemiparesis spontaneously following a general question about their complaint s-suffered from, and mentioned, other neurological deficits such as dysarthria, ptosis,or headache. However, they immediately acknowledged their paresis when t hey were asked about the strength of theirlimbs. Their other deficits clearly ha d a greater impact. These patients had significantly milder paresis than those w ho denied their disorder even when asked directly about their limbs.Conclusions: Patients who do not mention their paresis spontaneously but do so when question ed about it directly should not be diagnosed having “anosognosia. " If this mor e conservative cut off criterion is applied to the data of the present as well a s previous studies, a frequency of between 10%and 18%for anosognosia for hemip aresis is obtained in unselected samples of acute hemiparetic stroke patients. T he incidence thus seems smaller than previously assumed.