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108 Publications visible to you, out of a total of 108
Genetic Variations Associated with Brain Disorders: Focus on Synaptic Plasticity and Apoptosis Regulatory Genes in Schizophrenia, Posttraumatic Stress Disorder and Ischemic Stroke

Abstract (Expand)

Epidemiologic, clinical and experimental data indicates that a majority of brain disorders including schizophrenia (SCZ), posttraumatic stress disorder (PTSD), and ischemic stroke (IS) are multifactorial … disorders with strong and complex genetic component. Identification of all genetic variations associated with these disorders may sufficiently contribute to understanding of their basic pathomechanisms and encourage development of new innovative approaches to their early diagnosis and treatment. The aim of this review article is to provide overview of our recent studies on evaluation of potential association of SCZ, PTSD and IS with functional single nucleotide polymorphisms (SNPs) of synaptic plasticity and apoptosis regulatory genes in Armenian population. Here, our attention was focused on genes encoding netrin G1 (NTNG1), brain-derived neurotrophic factor (BDNF), complexin-2 (CPLX2), nerve growth factor (NGF) and its receptor (NGFR), annexin family proteins - annexin A5 and annexin A11 (ANXAV, ANXA11), and B-cell lymphoma 2 (Bcl-2) family proteins - Bcl-2 proper and Bcl-2-associated X protein (BCL2, BAX). Genomic DNA samples of diseased and healthy individuals were genotyped for a number of SNPs of the mentioned genes using polymerase chain reaction with sequence-specific primers (PCR-SSP). The significance of differences in genotype and allele frequencies and minor allele carriage between patients and healthy control subjects was determined using Pearson’s Chi-square test. P-values less than 0.05 were considered statistically significant. Significant associations were found between: (1) SCZ and BDNF rs6265, CPLX2 rs1366116, rs3892909, NGF rs6330, rs4839435, NGFR rs734194, rs11466155, rs2072446, ANXAV rs11575945, BAX rs1057369 SNPs; (2) PTSD and CPLX2 rs1366116, BCL2 rs956572 SNPs; (3) IS and NTNG1 rs628117, CPLX2 rs1366116, ANXAV rs11575945 SNPs. The obtained results indicated the involvement of genetically determined alterations in synaptic plasticity and apoptosis in pathomechanisms of SCZ, PTSD and IS. The minor T allele of the CPLX2 gene rs1366116 polymorphism represents risk factor for all studied diseased conditions indicating important functional significance of this genetic variation in maintenance of synaptic plasticity. Another important conclusion of these studies is that minor alleles of some polymorphic variants of genes, encoding synaptic plasticity and apoptosis regulatory proteins, may play a protective role relative to SCZ decreasing the risk for development of this disorder. In summary, our studies emphasize the important contribution of changes in synaptic plasticity and apoptosis regulation to pathomechanisms of SCZ, PTSD, and IS as well as significant input of genetic factors to these changes.

Authors: Anna Boyajyan, Ani Stepanyan, Diana Avetyan, Hovsep Ghazaryan, Sofi Atshemyan, Roksana Zakharyan, Kristina Pirumyan, Gohar Tsakanova

Date Published: 30th May 2014

Publication Type: Journal

Brain-derived neurotrophic factor blood levels are decreased in schizophrenia patients and associate with rs6265 genotypes

Abstract (Expand)

Objectives: A growing number of studies implicate brain-derived neurotrophic factor (BDNF), an important promoter of synaptic transmission and neural plasticity, in the pathogenesis of schizophrenia. … However, the existing data are controversial, that may reflect population differences between studied groups. Design and methods: In the present study we performed a comparative analysis of BDNF plasma levels and its relation with rs6265 (G196A; Val66Met) polymorphism of BDNF gene (BDNF) in schizophrenia-affected and healthy subjects (controls) of the Armenian population. To check the influence of antipsychotics on BDNF plasma levels both medicated and non-medicated patients were involved in this study. Patients with paranoid form of schizophrenia chronically treated with typical antipsychotics (n=103), age- and sex-matched controls (n=105), and 25 antipsychotic-naive first-episode schizophrenia patients were involved. The levels of BDNF in the blood plasma were measured with a solid-phase enzyme-linked immunosorbent assay. Results: Decreased plasma levels of BDNF in both medicated and non-medicated schizophrenia patients compared to controls were observed. No significant difference in BDNF levels between medicated and non-medicated patients was detected. It was also detected that, compared to individuals homozygous for the standard allele (G/G) of rs6265, carriers of the rs6265 minor allele (A/G+A/A), which is significantly more frequent in schizophrenia patients than in controls, had decreased BDNF levels. Conclusions: The data obtained suggested that the pathogenesis of schizophrenia is characterized by genetically predetermined decreased blood levels of BDNF. These results indicated that genetically determined alterations of neuroimmune modulators may be among the risk factors of schizophrenia and contribute to disease-specific pathologic changes in functional activity of both the neuronal synaptic plasticity and the immune system. Keywords: Brain-derived neurotrophic factor; Plasma levels; Schizophrenia; rs6265 Polymorphism.

Authors: Roksana Zakharyan, Anna Boyajyan

Date Published: 5th Apr 2014

Publication Type: Journal

Inflammatory cytokine network in schizophrenia

Abstract (Expand)

Objectives: The purpose of this review is to analyse, sum up and discuss the available literature on the role of inflammation and inflammatory cytokines in the pathogenesis of schizophrenia. Methods: …: An electronic literature search of peer-reviewed English language articles using Pubmed was undertaken. These articles together with those published by us provided the background for the present review. Results: An overview of the available literature on this issue clearly demonstrated the alterations in mRNA and protein expression levels of several proinflammatory and chemotactic cytokines in patients with schizophrenia. Importantly, some of these changes are genetically determined. It was noteworthy that, depending on the study population, some variations of the data obtained are detected. Conclusions: Altered inflammatory cytokine production, both genetically and environmentally determined, is implicated in schizophrenia and contributes to disease-associated low-grade systemic inflammation. Proinflammatory and chemotactic cytokines and their receptors may represent additional therapeutic targets for treatment of schizophrenia.

Authors: Roksana Zakharyan, Anna Boyajyan

Date Published: 16th Sep 2013

Publication Type: Journal

Inflammatory Responses to Salmonella Infections Are Serotype-Specific.

Abstract (Expand)

The main purpose of this study was to investigate the profile of inflammatory response in patients with acute salmonellosis caused by two serotypes of Salmonella enterica, S. Enteritidis and S. … Typhimurium, as well as in convalescent patients with previous acute disease caused by S. Enteritidis. Patients with acute disease showed significantly elevated levels of IL-1β, IL-17, IL-10, and calprotectin compared to healthy control subjects. In convalescent patients, these markers were also significantly elevated, with the exception of IL-1β. Multivariate statistical analyses with the use of these variables produced models with a good predictive accuracy resulting in excellent separation of the diseased and healthy cohorts studied. Overall, the results suggest that the profile of inflammatory response in this disease is determined, to a significant degree, by the serotype of Salmonella, and the profile of certain cytokines and calprotectin remains abnormal for a number of months following the acute disease stage.

Authors: Zhanna Ktsoyan, Karine Ghazaryan, Gayane Manukyan, Anush Martirosyan, Armine Mnatsakanyan, Karine Arakelova, Zaruhi Gevorgyan, Anahit Sedrakyan, Ara Asoyan, Anna Boyajyan, Rustam Aminov

Date Published: 16th Sep 2013

Publication Type: Journal

Markers of apoptotic dysfunctions in schizophrenia

Abstract (Expand)

According to the modern concepts, alterations of apoptosis and its genetic regulation are associated with the etiopathogenesis of schizophrenia, which is observed at both the brain and peripheral blood … levels. However, studies of this phenomenon are at the initial stage, and the molecular and cellular mechanisms that underlie the anomalies of the processes of apoptotic cell death in schizophrenia are unclear. In the present study, we determined the levels of apoptotic markers, annexin A5 and H-ficolin proteins, in the sera of patients with chronic and first-episode schizophrenia and healthy subjects to test the proposed relationship between schizophrenia and the rs11575945 (−1C/T) single-nucleotide substitution (functional polymorphism) of Kozak consensus sequence in the regulatory region of the annexin A5 gene. Methods of a solid-phase enzyme-linked immunosorbent assay and polymerase chain reaction with allele-specific primers were used. It was shown that the pathogenesis of schizophrenia is characterized by an increased rate of apoptosis, which is more pronounced in the case of the first-episode neuroleptic-free patients than in the case of chronic patients that receive typical neuroleptic haloperidol. It was also shown that the rs11575945 polymorphism of the annexin A5 gene is associated with schizophrenia, and its minor allele is responsible for higher levels of the annexin A5 protein in the blood and represents one of the risk factors for the development of this disease.

Authors: A. S. Boyajyan, A. S. Chavushyan, R. V. Zakharyan, G. M. Mkrtchyan

Date Published: 15th Aug 2013

Publication Type: Journal

Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome.

Abstract (Expand)

In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever (FMF), the gut microbial diversity is specifically restructured, which also results in the altered … profiles of microbial long chain fatty acids (LCFAs) present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles. Moreover, it results in the formation of new distinct microbial LCFA clusters, which are well separated from the corresponding values in healthy controls and FMF patients without the therapy. We hypothesize that the therapy alters the proinflammatory network specific for the disease, with the concomitant changes in gut microbiota and the corresponding microbial LCFAs in the metabolome.

Authors: Zhanna A Ktsoyan, Natalia V Beloborodova, Anahit M Sedrakyan, George A Osipov, Zaruhi A Khachatryan, Gayane P Manukyan, Karine A Arakelova, Alvard I Hovhannisyan, Arsen A Arakelyan, Karine A Ghazaryan, Magdalina K Zakaryan, Rustam I Aminov

Date Published: 28th Jan 2013

Publication Type: Journal

Interleukin‐6 promoter polymorphism and plasma levels in patients with schizophrenia

Abstract (Expand)

Schizophrenia is a severe psychiatric disease with inflammatory component. Several studies indicated the increased blood levels of proinflammatory interleukin-6 cytokine in schizophrenia. However, only … limited studies explored the relationship between excess production and genetic variations of this cytokine in schizophrenia, and the results were controversial. Here, we investigated possible association of the interleukin-6 gene (IL6) rs1800795 (–174G/C) polymorphism with schizophrenia and relationship between this polymorphism and interleukin-6 protein (IL-6) blood levels. This polymorphism was found by other researchers to associate with different transcription rates and different plasma levels of IL-6. A total of 208 unrelated Armenians were genotyped by polymerase chain reaction with sequence-specific primers, and IL-6 levels were assessed by enzyme-linked immunosorbent assay. The IL6 rs1800795 alleles and genotypes in both groups were in Hardy–Weinberg (H–W) equilibrium. We found that rs1800795*C allele [38% vs 24%, P = 0.002, odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.18–2.14] and its carriers (62% vs 42%, P = 0.003, OR = 2.28, 95% CI: 1.13–1.94) were more frequent in patients than in controls. IL-6 in patients was 1.5-fold higher than in controls (mean ± SD: 6.41 ± 2.47 pg/ml vs 4.15 ± 1.42 pg/ml, P = 1.9E–19). In both groups, higher IL-6 in rs1800795 GG compared to rs1800795*C allele carriers was observed (GG vs GC + CC, patients: 7.02 ± 2.83 pg/ml vs 5.39 ± 1.2 pg/ml, P = 0.0006; controls: 5.21 ± 1.17 pg/ml vs 3.38 ± 1.03 pg/ml, P = 1.6E–15). In conclusion, we report an association of IL6 rs1800795 and higher IL-6 with schizophrenia. We also conclude that IL6 rs1800795*C allele is linked to increased IL-6 blood levels and may be a risk factor for schizophrenia development at least in Armenian population.

Authors: R. Zakharyan, M. Petrek, A. Arakelyan, F. Mrazek, S. Atshemyan, A. Boyajyan

Date Published: 10th May 2012

Publication Type: Journal

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