scholarly journals NDRG2 Expression Correlates with Neurofibrillary Tangles and Microglial Pathology in the Ageing Brain

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.

2019 ◽  
Vol 20 (23) ◽  
pp. 5852 ◽  
Author(s):  
Zaitsev ◽  
Malkin ◽  
Postnikova ◽  
Smolensky ◽  
Zubareva ◽  
...  

Epilepsy is a common neurological disorder. Despite the availability of a wide range of antiepileptic drugs, these are unsuccessful in preventing seizures in 20–30% of patients. Therefore, new pharmacological strategies are urgently required to control seizures. Modulation of glutamate uptake may have potential in the treatment of pharmacoresistant forms of epilepsy. Previous research showed that the antibiotic ceftriaxone (CTX) increased the expression and functional activity of excitatory amino acid transporter 2 (EAAT2) and exerted considerable anticonvulsant effects. However, other studies did not confirm a significant anticonvulsant effect of CTX administration. We investigated the impacts of CTX treatment on EAAT expression and glutamatergic neurotransmission, as well its anticonvulsant action, in young male Wistar rats. As shown by a quantitative real-time polymerase chain reaction (qPCR) assay and a Western blot analysis, the mRNA but not the protein level of EAAT2 increased in the hippocampus following CTX treatment. Repetitive CTX administration had only a mild anticonvulsant effect on pentylenetetrazol (PTZ)-induced convulsions in a maximal electroshock threshold test (MEST). CTX treatment did not affect the glutamatergic neurotransmission, including synaptic efficacy, short-term facilitation, or the summation of excitatory postsynaptic potentials (EPSPs) in the hippocampus and temporal cortex. However, it decreased the field EPSP (fEPSP) amplitudes evoked by intense electrical stimulation. In conclusion, in young rats, CTX treatment did not induce overexpression of EAAT2, therefore exerting only a weak antiseizure effect. Our data provide new insight into the effects of modulation of EAAT2 expression on brain functioning.


2020 ◽  
Vol 21 (12) ◽  
pp. 1193-1201
Author(s):  
Abdullah Al Mamun ◽  
Md. Mosiqur Rahman ◽  
Sonia Zaman ◽  
Mst Shirajum Munira ◽  
Md. Sahab Uddin ◽  
...  

: The ubiquitin (Ub)-proteasome system (UPS) targets various cellular proteins for degradation. It has been found that defects in the UPS play a crucial role in the pathogenesis of Alzheimer's disease (AD), as the existence of Ub immunoreactivity in AD-linked neuronal inclusions, including neurofibrillary tangles, is observed in all types of AD cases. Current investigations have shown that components of the UPS can be connected with the early stage of AD, which is characterized by synaptic dysfunction, and to the late phases of the disease, marked by neurodegeneration. Although the significance of UPS in the pathogenesis of AD has been emphasized, targeted treatment at the main components of these pathways has a great perspective in advancing new therapeutic interventions for AD. In this review, we emphasize the relationship between UPS and AD pathology. We also represent the recent therapeutic advancements targeting UPS components in AD.


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.


Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.


2019 ◽  
Vol 58 (2) ◽  
pp. 249-259
Author(s):  
Joseph Acquisto

This essay examines a polemic between two Baudelaire critics of the 1930s, Jean Cassou and Benjamin Fondane, which centered on the relationship of poetry to progressive politics and metaphysics. I argue that a return to Baudelaire's poetry can yield insight into what seems like an impasse in Cassou and Fondane. Baudelaire provides the possibility of realigning metaphysics and politics so that poetry has the potential to become the space in which we can begin to think the two of them together, as opposed to seeing them in unresolvable tension. Or rather, the tension that Baudelaire animates between the two allows us a new way of thinking about the role of esthetics in moments of political crisis. We can in some ways see Baudelaire as responding, avant la lettre, to two of his early twentieth-century readers who correctly perceived his work as the space that breathes a new urgency into the questions of how modern poetry relates to the world from which it springs and in which it intervenes.


2019 ◽  
Vol 48 (1) ◽  
pp. 83-101
Author(s):  
Cameron McKay

During the late nineteenth and early twentieth century penologists began to explore the possibility that environment and upbringing, as opposed to individual choice, were the causes criminality. The Prison Commissioners for Scotland, the devolved body who administered prisons north of the border, were not immune to this wider trend. Smith has argued that from the 1890s onwards the Commissioners began to accept that criminality was caused by social problems, namely alcoholism, but also parental neglect, poor education and poverty. In their efforts to test these new criminological theories, the Commissioners began to make more careful enquiries into the backgrounds of their charges. From 1896 to 1931 the Commissioners interviewed a sample of prisoners each year and included the findings in their annual report. Although the main focus of these interviews was on the upbringing and drinking habits of prisoners; by the 1900s the Commissioners seem to have added irreligion to the growing list of etiological causes of crime, and from 1903 onwards prisoners were asked to give details on their religious habits. Although it is debateable how much the Prison Commissioners revealed about the relationship between religion and crime, they did however provide a useful insight into the religiosity of the average prisoner.


2011 ◽  
Vol 5 (2) ◽  
pp. 297-332
Author(s):  
Kate Zebiri

This article aims to explore the Shaykh-mur?d (disciple) or teacher-pupil relationship as portrayed in Western Sufi life writing in recent decades, observing elements of continuity and discontinuity with classical Sufism. Additionally, it traces the influence on the texts of certain developments in religiosity in contemporary Western societies, especially New Age understandings of religious authority. Studying these works will provide an insight into the diversity of expressions of contemporary Sufism, while shedding light on a phenomenon which seems to fly in the face of contemporary social and religious trends which deemphasize external authority and promote the authority of the self or individual autonomy.


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