Research on the Relationship Between Schizophrenia and Excitatory Amino Acid Transporter 1 Gene Based on Nanogold Amplification Technology

2021 ◽  
Vol 21 (2) ◽  
pp. 1278-1285
Author(s):  
Shuang Zheng ◽  
Wen Xie ◽  
Longcai Fei ◽  
Nannan Zhu

Schizophrenia is one of the most common central nervous system diseases, which is caused by abnormal discharge of neurons in the brain. Its occurrence and development are affected by both genetic and environmental factors. The variation of gene level can affect the development of schizophrenia and the treatment of prognosis by affecting the susceptibility, clinical phenotype and drug response. At present, the research results of susceptibility genes screened by candidate gene association research are not consistent. The method of gene recognition on DNA was studied by QCM and nano gold composite. By using this method, the enantioselective recognition of cysteine on cyclodextrin self-assembled membrane was studied. In this study, EAAT1 gene, which is highly expressed in astrocytes, was used as a candidate gene to analyze the relationship between polymorphism and schizophrenia. The experimental results show that the introduction of nano gold can significantly improve the sensing signal, detection sensitivity and gene differentiation. In addition, this study suggested that EAAT1 gene might be a susceptibility gene of schizophrenia in the population. The results showed that a common SNP allele rs1030239-g was the risk factor (83.8% vs. 79.2%, P = 0.00067, or = 1.35, 95% CI = 1.08-1.69). The results showed that A-T-G increased the risk of schizophrenia.

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Mostafa I. Waly ◽  
Mady Hornig ◽  
Malav Trivedi ◽  
Nathaniel Hodgson ◽  
Radhika Kini ◽  
...  

Although autism is first and foremost a disorder of the central nervous system, comorbid dysfunction of the gastrointestinal (GI) and immune systems is common, suggesting that all three systems may be affected by common molecular mechanisms. Substantial systemic deficits in the antioxidant glutathione and its precursor, cysteine, have been documented in autism in association with oxidative stress and impaired methylation. DNA and histone methylation provide epigenetic regulation of gene expression during prenatal and postnatal development. Prenatal epigenetic programming (PrEP) can be affected by the maternal metabolic and nutritional environment, whereas postnatal epigenetic programming (PEP) importantly depends upon nutritional support provided through the GI tract. Cysteine absorption from the GI tract is a crucial determinant of antioxidant capacity, and systemic deficits of glutathione and cysteine in autism are likely to reflect impaired cysteine absorption. Excitatory amino acid transporter 3 (EAAT3) provides cysteine uptake for GI epithelial, neuronal, and immune cells, and its activity is decreased during oxidative stress. Based upon these observations, we propose that neurodevelopmental, GI, and immune aspects of autism each reflect manifestations of inadequate antioxidant capacity, secondary to impaired cysteine uptake by the GI tract. Genetic and environmental factors that adversely affect antioxidant capacity can disrupt PrEP and/or PEP, increasing vulnerability to autism.


2020 ◽  
Vol 21 (1) ◽  
pp. 340
Author(s):  
Motaz M. Fadul ◽  
Claire J. Garwood ◽  
Rachel Waller ◽  
Navonna Garrett ◽  
Paul R. Heath ◽  
...  

Astrocytes play a major role in the pathogenesis of a range of neurodegenerative diseases, including Alzheimer’s disease (AD), undergoing dramatic morphological and molecular changes that can cause potentially both beneficial and detrimental effects. They comprise a heterogeneous population, requiring a panel of specific phenotype markers to identify astrocyte subtypes, changes in function and their relation to pathology. This study aimed to characterise expression of the astrocyte marker N-myc downstream regulated gene 2 (NDRG2) in the ageing brain, investigate the relationship between NDRG2 and a panel of astrocyte markers, and relate NDRG2 expression to pathology. NDRG2 specifically immunolabelled the cell body and radiating processes of astrocytes in the temporal cortex of the Cognitive Function and Ageing Study (CFAS) neuropathology cohort. Expression of NDRG2 did not correlate with other astrocyte markers, including glial fibrillary acidic protein (GFAP), excitatory amino acid transporter 2 (EAAT2) and glutamine synthetase (GS). NDRG2 showed a relationship to AT8+ neurofibrillary tangles (p = 0.001) and CD68+ microglia (p = 0.047), but not β-amyloid plaques or astrocyte nuclear γH2AX immunoreactivity, a marker of DNA damage response. These findings provide new insight into the astrocyte response to pathology in the ageing brain, and suggest NDRG2 may be a potential target to modulate this response.


2013 ◽  
Vol 107 (2) ◽  
pp. 375-381 ◽  
Author(s):  
KRISTEN DIANE DEPPE ◽  
SCOTT F. STOLTENBERG ◽  
KEVIN B. SMITH ◽  
JOHN R. HIBBING

Recently in this journal, Charney and English (2012) presented an extensive critique of candidate gene association studies using the widely noted Fowler and Dawes (2008) article on the relationship between self-reported voter turnout and both 5-HTT (serotonin transporter) and MAOA (monoamine oxidase A) as the driving example of their evaluation. Reanalysis of the Fowler and Dawes data by Charney and English, based on four critiques of candidate gene studies, led to the conclusion that neither polymorphism is related to variations in turnout. We add to this empirical debate by conducting an independent test using an original dataset containing 5-HTT data and two separate participation variables: self-reported participation and actual voting records. Our results confirm the original conclusions by Fowler and Dawes on 5-HTT, but also support several of the critiques suggested by Charney and English. We conclude by offering suggestions for the way candidate gene association studies should be interpreted by the discipline and processed by journal editors.


2017 ◽  
Vol 114 (22) ◽  
pp. 5719-5724 ◽  
Author(s):  
Isaac D. Zike ◽  
Muhammad O. Chohan ◽  
Jared M. Kopelman ◽  
Emily N. Krasnow ◽  
Daniel Flicker ◽  
...  

Obsessive-compulsive disorder (OCD) is a chronic, disabling condition with inadequate treatment options that leave most patients with substantial residual symptoms. Structural, neurochemical, and behavioral findings point to a significant role for basal ganglia circuits and for the glutamate system in OCD. Genetic linkage and association studies in OCD point to SLC1A1, which encodes the neuronal glutamate/aspartate/cysteine transporter excitatory amino acid transporter 3 (EAAT3)/excitatory amino acid transporter 1 (EAAC1). However, no previous studies have investigated EAAT3 in basal ganglia circuits or in relation to OCD-related behavior. Here, we report a model of Slc1a1 loss based on an excisable STOP cassette that yields successful ablation of EAAT3 expression and function. Using amphetamine as a probe, we found that EAAT3 loss prevents expected increases in (i) locomotor activity, (ii) stereotypy, and (iii) immediate early gene induction in the dorsal striatum following amphetamine administration. Further, Slc1a1-STOP mice showed diminished grooming in an SKF-38393 challenge experiment, a pharmacologic model of OCD-like grooming behavior. This reduced grooming is accompanied by reduced dopamine D1 receptor binding in the dorsal striatum of Slc1a1-STOP mice. Slc1a1-STOP mice also exhibit reduced extracellular dopamine concentrations in the dorsal striatum both at baseline and following amphetamine challenge. Viral-mediated restoration of Slc1a1/EAAT3 expression in the midbrain but not in the striatum results in partial rescue of amphetamine-induced locomotion and stereotypy in Slc1a1-STOP mice, consistent with an impact of EAAT3 loss on presynaptic dopaminergic function. Collectively, these findings indicate that the most consistently associated OCD candidate gene impacts basal ganglia-dependent repetitive behaviors.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yufang Xiang ◽  
Yuanyuan Zheng ◽  
Shaobo Liu ◽  
Gang Liu ◽  
Zhi Li ◽  
...  

AbstractWestern blotting (WB) is one of the most widely used techniques to identify proteins as well as post translational modifications of proteins. The selection of electroblotted membrane is one of the key factors affecting the detection sensitivity of the protein which is transferred from gel to membrane in WB. The most common used membranes are polyvinylidene fluoride (PVDF) and nitrocellulose (NC) membranes. Which membrane of these two is more suitable for WB has not been reported so far. Here, by incubating proteins which were transferred to PVDF or NC membranes with a series of antibodies and different types of lectins, we investigated the relationship between the binding ability of these two membranes to proteins or glycoproteins and the molecular weight of the target protein. The antibody re-probed ability of the two membranes was also explored. Moreover, we verified the above results by directly incubating proteins having different molecular weights onto PVDF or NC membranes. Bound proteins were stained with direct blue-71, and the staining intensity was quantitated by scanning and densitometry.


2001 ◽  
Vol 178 (S41) ◽  
pp. s128-s133 ◽  
Author(s):  
Nick Craddock ◽  
Ian Jones

BackgroundA robust body of evidence from family, twin and adoption studies demonstrates the importance of genes in the pathogenesis of bipolar disorder. Recent advances in molecular genetics have made it possible to identify these susceptibility genes.AimsTo present an overview for clinical psychiatrists.MethodReview of current molecular genetics approaches and emerging findings.ResultsOccasional families may exist in which a single gene plays a major role in determining susceptibility, but the majority of bipolar disorder involves more complex genetic mechanisms such as the interaction of multiple genes and environmental factors. Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest include chromosomes 4p16, 12q23–q24, 16p13, 21q22, and Xq24–q26. Candidate gene association studies are in progress but no robust positive findings have yet emerged.ConclusionIt is almost certain that over the next few years the identification of bipolar susceptiblity genes will have a major impact on our understanding of disease pathophysiology. This is likely to lead to major improvements and treatment in patient care, but will also raise important ethical issues.


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