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Journal of Behavioral and Brain Science 2011年第3期1卷 172-180页

作者： Eugenia Kutcher Alexey Egorov elena filatova Kristina Kulagina Nadezhda Chernikova 不详

Last years the intake of energy drinks (drinks containing caffeine and alcohol) both in young men and women has been increased. However the investigators do not pay attention to the analysis of gender differences. The goal of the study was the investigation of ethanol and caffeine influence on the alcohol preference formation and behavior in male and female rats under the conditions of long-term experiment. It has been found that six month intake of caffeine, ethanol and their combination has led to the increase of alcohol preference both in male and female rats. Alcohol preference was formed earlier in rats consumed combination of caffeine with ethanol, later on in rats consumed ethanol. In animals consumed caffeine the strong alcohol preference did not form up to the end of the experiment. Alcohol preference was higher in female rats consuming caffeine with ethanol and pure ethanol solution compared to male rats. .Behavioral activity significantly increased in females consumed caffeine and caffeine with ethanol, compared to animals received ethanol and controls. Similar tendency was observed in male rats. The anxiety level was significantly higher in females rats in all experimental groups compared to controls, while males did not demonstrate increased anxiety.

关键词： Ethanol Caffeine Two-Bottle Test Behavioral Activity Anxiety

Synthetic Peptides Affect the Expression of Gdnf and Gdnf Receptors in Rats with 6-OHDA-Induced PD-Like Parkinsonism

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World Journal of Neuroscience 2016年第4期6卷 243-259页

作者： elena V. filatova Maria I. Shadrina Timur A. Kolomin Ludmila A. Andreeva Nikolay F. Myasoedov Petr A. Slominsky Institute of Molecular Genetics Russian Academy of Sciences Moscow Russia

Parkinson’s disease (PD) is the second most common severe neurodegenerative disorder. It is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Unfortunately, PD remains incurable. Therapy based on regulatory peptides, particularly neuroprotective peptides, which can sustain or activate neuron plasticity to enable their survival and function in difficult environments and after violated homeostasis, is a promising approach to cure PD. Some studies show that the synthetic analogs of natural peptides may be used as an etiological or at least a complementary therapy in PD. Therefore, in the present pilot study, we investigated the effects of the synthetic peptides Semax and dopamine neuron stimulating peptide (DNSP-5), and a new synthetic Semax-DNSP-5 hybrid peptide (SD) on the functioning of brain neurons. An analysis of the levels of dopamine (DA), noradrenaline (NA), 5-hydroxytriptamine (5-HT), an expression analysis of Gdnf and Gdnf receptor genes Gfra1, Gfra2, Gfra3, Gfra4, and Gfral in various regions of the brain of rats with 6-OHDA-induced PD-like parkinsonism, and a study of the motor activity of the rats in an “open field” test showed that DNSP-5 and SD elevated the level of DA in the nonlesioned striatum. DNSP-5 also increased the expression of Gfra1 and Gfra2 in the nonlesioned striatum and lesioned substantia nigra (SN) which suggested that DNSP-5 had compensatory and neuroprotective properties. SD demonstrated similar, albeit less pronounced effects to DNSP-5 on DA metabolism and gene expression. Of the peptides studied, only SD tended to increase the horizontal and vertical activity of rats. In conclusion, these findings suggest that DNSP-5 and SD have potential neuroprotective properties and may stimulate the surviving DA neurons.

关键词： 6-OHDA Parkinson’s Disease Semax DNSP-5 Gene Expression

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

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Neuroscience & Medicine 2013年第4期4卷 208-214页

作者： Anelya Kh. Alieva Maria I. Shadrina elena V. filatova Vera V. Ustinova Ekaterina Yu Fedotova Alexey V. Karabanov Sergey N. Illarioshkin Petr A. Slominsky Institute of Molecular Genetics Russian Academy of Sciences Moscow Russia Research Centre of Neurology Russian Academy of Medical Sciences Moscow Russi Research Centre of Neurology Russian Academy of Medical Sciences Moscow 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.

关键词： Parkinson’s Disease Expression Analysis SNCA SNP

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

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Advances in Parkinson's Disease 2013年第1期2卷 28-30页

作者： elena V. filatova Maria I. Shadrina Ekaterina Y. Fedotova Irina A. Ivanova-Smolenskaya Sergei N. Illarioshkin Svetlana A. Limborska Petr A. Slominsky Institute of Molecular Genetics Russian Academy of Sciences Moscow Russia Research Centre of Neurology Russian Academy of Medical Sciences Moscow Russia

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.

关键词： Parkinson’s Disease Point Mutations Single-Nucleotide Polymorphisms

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

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Advances in Bioscience and Biotechnology 2013年第6期4卷 28-35页

作者： Maria I. Shadrina elena V. filatova Anelya Kh. Alieva Alla V. Stavrovskaya Rudolph M. Khudoerkov Svetlana A. Limborska Sergei N. Illarioshkin Petr A. Slominsky Institute of Molecular Genetics Russian Academy of Sciences Moscow Russia Scientific Centre of Neurology Russian Academy of Medical Sciences Moscow Russia

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 extra

关键词： 6-OHDA Parkinson’s Disease Transcriptome