Involvement of Anomalous Apoptosis in Impairments to Synaptic Plasticity in Post-Traumatic Stress Disorder

Mkrtchyan, G.; Boyadzhyan, A. S.; Avetyan, Diana; Sukiasyan, S. G.

doi:10.1007/s11055-014-9930-5

Cited by 6 publications

(8 citation statements)

References 40 publications

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“…Increased levels of this protein induce development of inflammatory reactions [70][71][72], which are characteristic features of SCZ [22], PTSD [14], and IS [73]. The increased serum levels of this protein were found by us in IS [19] and SCZ [25] and by other research group in SCZ [74], and we also detected the decreased levels of this protein in PTSD [15,18]. The rs11575945 SNP (-1C/T) in the Kozak consensus sequence of the regulatory part of the ANXAV gene plays a key role in the initiation of transcription [75], and the rs1157945*T minor allele of this gene correlates with the higher level of synthesis of this protein in the blood [75].…”

Section: Resultssupporting

confidence: 72%

“…It has been shown that downregulation of complexin-2 might lead to changes in neurotransmitter release and deficit in synaptic transmission causing significant cognitive and behavioral abnormalities and is implicated in pathogenesis and progression of many diseased conditions characterized by altered cognitive function and behavior [53,54]. In particular, decreased expression levels of this protein in the prefrontal cortex, cerebellum, and hippocampus of patients with SCZ were observed [55], and our own studies revealed decreased production of complexin-2 protein in the blood of SCZ [30] and PTSD [14,15,18] affected subjects. The results obtained in our study with the CPLX2 gene indicated that the rs1366116*T minor allele of this gene was overrepresented in SCZ, PTSD, and IS patients when compared to HI suggesting a positive association of this polymorphism with these diseased conditions [26,30].…”

Section: Resultsmentioning

confidence: 90%

“…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. Several studies, including our own, suggest implication of alterations in synaptic neuronal plasticity and apoptosis to pathophysiology of SCZ, PTSD, and IS [10][11][12][13][14][15][16][17][18][19]. This review provides overview of our recent studies (including published [20][21][22][23][24][25][26][27][28][29][30][31][32][33] and unpublished data) on evaluation of potential association of SCZ, PTSD and IS with functional single nucleotide polymorphisms (SNPs) of synaptic plasticity and apoptosis regulatory genes.…”

Section: Introductionmentioning

confidence: 99%

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Genetic Variations Associated with Brain Disorders: Focus on Synaptic Plasticity and Apoptosis Regulatory Genes in Schizophrenia, Posttraumatic Stress Disorder and Ischemic Stroke

Boyajyan¹

2014

IJGG

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Abstract: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.

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Section: Resultssupporting

confidence: 72%

Section: Resultsmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Genetic Variations Associated with Brain Disorders: Focus on Synaptic Plasticity and Apoptosis Regulatory Genes in Schizophrenia, Posttraumatic Stress Disorder and Ischemic Stroke

Boyajyan¹

2014

IJGG

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“…Our previous study showed that the blood level of annexin-А5 was significantly lower and the levels of TNF-α were significantly higher in PTSD patients. This low apoptosis rate may be one of the factors responsible for development of PTSD-associated low-grade inflammation [26]. Thus, our current research suggests that the low level of BAX/Bcl-2 ratio in peripheral blood can be explained by chronic low-grade inflammatory response process in PTSD.…”

Section: Discussionmentioning

confidence: 59%

Association of Bax and Bcl-2 Functional Polymorphisms and Protein Levels with Posttraumatic Stress Disorder

Avetyan¹,

Arakelyan²,

Mkrtchyan³

2018

JBM

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Background: Posttraumatic stress disorder (PTSD) is an anxiety disease influenced by both environmental and genetic factors, which affects a patient's quality of life and social stability. Recent studies have shown that the pathogenesis of PTSD is associated with apoptosis; however, the molecular mechanisms that cause such damage are not well-understood. Also it is unclear whether these pathologic alterations are genetically determined or caused by other factors. The aim of this study was to investigate the genetic association of functional polymorphisms in genes coding for apoptosis-related Bcl-2 and Bax proteins with PTSD as well as proteins levels in the blood of affected subjects. Methods: The study groups consisted of 200 combat veterans with PTSD and an equal number of healthy subjects with no family-or past-history of any psychiatric disorders. Bax and Bcl-2 proteins levels in blood were measured by ELISA. DNA samples were genotyped for SNPs using PCR-SSP. Results: According to our results, PTSD patients are characterized by increased levels of apoptotic proteins and the imbalance in the Bax/Bcl-2 ratio compared to healthy subjects. Our results also demonstrate that rs956572*A minor allele of the BCL2 gene was overrepresented in patients with PTSD compared to healthy subjects. Conclusions: The results implicate Bcl-2 and Bax in pathogenesis of PTSD on genetic and protein levels, though further studies on enlarged cohort and in different populations are required.

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“…Appropriate apoptosis can maintain the homeostasis of the body, but abnormal apoptosis inevitably indicates the disorder of the internal environment of the body. 51,52 The apoptosis of immune cells is closely related to the regulation of the immune system, and is an important index to evaluate the changes of immune function. 53 As important regulators of apoptosis, the expressions of both anti-apoptotic proteins represented by Bcl2 and pro-apoptotic proteins represented by Bax and Caspase-3 determine the trend of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

<p>Regulatory Effect of Anwulignan on the Immune Function Through Its Antioxidation and Anti-Apoptosis in D-Galactose-Induced Aging Mice</p>

Gao

et al. 2020

CIA

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Background: Aging is a spontaneous and inevitable phenomenon of biology, which can lead to the gradual deterioration of tissues and organs. One of the age-related deterioration processes is immunosenescence, which leads to changes in the function of immune systems, including immune cells and associated cytokines. A proper modulation of immune responses can improve the age-related immunosenescence process and then reach healthy aging. Schisandra sphenanthera, a traditional Chinese medicine, has been used as both a medicine and a nutritional supplement for thousands of years. Anwulignan, a monomer compound of Schisandra sphenanthera lignans, has been reported to possess an immunomodulatory effect. Therefore, this study was designed to further explore whether Anwulignan could also modulate the immune functions in aging model mice and the underlying mechanism. Methods: D-galactose (D-gal) is often used as an inducer of immunosenescence in animals. In this study, a mice model was created by subcutaneous D-gal (220 mg kg −1) for successive 42 days. Then, the blood and spleen tissue samples were taken for the analysis and observation of cytokine levels, immunoglobulin levels, leukocyte numbers, and the phagocytic activity of macrophages, as well as the histological changes, the proliferation ability of lymphocytes, and the biochemical parameters in the spleen tissue. Results: Anwulignan significantly increased the serum levels of IL-2, IL-4, IFN-γ, lgG, lgM, and lgA, decreased the content of TNF-α and IL-6 in the aging mice, and increased the blood leukocyte number, the phagocytic activity, the lymphocyte proliferation, and the spleen index in vitro. Anwulignan also significantly increased the activities of SOD and GSH-Px, decreased the contents of MDA and 8-OHdG in the spleen tissue, up-regulated the expressions of Nrf2, HO-1, and Bcl2, down-regulated the expressions of Keap1, Caspase-3, and Bax in the spleen cells, and reduced the apoptosis of spleen lymphocytes. Conclusion: Anwulignan can restore the immune function that is declined in D-gal-induced aging mice partly related to its antioxidant capacity by activating the Nrf2/ARE pathway and downstream enzymes, as well as its anti-apoptotic effect by regulating Caspase-3 and the ratio of Bcl2 to Bax in the spleen.

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Involvement of Anomalous Apoptosis in Impairments to Synaptic Plasticity in Post-Traumatic Stress Disorder

Cited by 6 publications

References 40 publications

Genetic Variations Associated with Brain Disorders: Focus on Synaptic Plasticity and Apoptosis Regulatory Genes in Schizophrenia, Posttraumatic Stress Disorder and Ischemic Stroke

Genetic Variations Associated with Brain Disorders: Focus on Synaptic Plasticity and Apoptosis Regulatory Genes in Schizophrenia, Posttraumatic Stress Disorder and Ischemic Stroke

Association of Bax and Bcl-2 Functional Polymorphisms and Protein Levels with Posttraumatic Stress Disorder

<p>Regulatory Effect of Anwulignan on the Immune Function Through Its Antioxidation and Anti-Apoptosis in D-Galactose-Induced Aging Mice</p>

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