1,720,965 research outputs found
METABOLIC CROSS-TALK BETWEEN ASTROCYTES AND NEURONS: IMPLICATIONS FOR ALZHEIMER’S DISEASE
Full text linkEsiste una forte correlazione tra l'ipometabolismo del glucosio, la disfunzione mitocondriale e lo stress ossidativo, elementi coinvolti nella patogenesi dei disturbi neurodegenerativi, come la malattia di Alzheimer (AD) [1]. Recenti evidenze suggeriscono che l'ipometabolismo avviene anche negli astrociti, i quali potrebbero perdere le loro normali capacità neuroprotettive ed essere coinvolti in malattie neurologiche determinando la progressione e l'esito del processo neuropatologico [2]. Lo scopo è stato quello di esplorare il ruolo degli astrociti nell’ innescare una cascata di effetti dannosi nei neuroni vicini e investigare un approccio in grado di limitare il danno in entrambi i tipi cellulari. Le colture primarie di astrociti corticali di ratto sono state sottoposte a gliceraldeide (GA) per indurre uno stress metabolico [3]. Lo studio è stato condotto per verificare l’influenza degli astrociti danneggiati sulla sopravvivenza neuronale. In particolare, sono stati valutati la vitalità cellulare, la produzione di ATP, lo stato infiammatorio e lo stress ossidativo negli astrociti trattati con GA e glutammato (glut), utilizzato come substrato alternativo. I risultati hanno indicato che l'esposizione a GA ha comportato un danno negli astrociti, dipendente dalla concentrazione, attivando la via del NF-kB e aumentando il rilascio di TNFα e i livelli di espressione dei trasportatori del glutammato, tutti questi aspetti sono stati mitigati dal trattamento con glut. La co-coltura di astrociti danneggiati con neuroni ha comportato una significativa riduzione della vitalità neuronale. L'esposizione al glutammato ha migliorato i livelli intracellulari di ATP e ridotto i marcatori dell'AD nei neuroni. Questo studio dimostra che gli astrociti con disfunzioni metaboliche possono contribuire al danno dei neuroni vicini nel contesto della AD ed evidenzia l'importanza della ricerca di terapie con target gli astrociti per valutare potenziali interventi neuroprotettivi in futuri studi sull'AD.
1. Nat Rev Neurosci 2019 Mar;20(3):148-160.
2. Front Neurol. 2021; 12: 619626.
3. Cells. 2021 Aug 17;10(8):2109.There is a strong correlation between glucose hypometabolism mitochondrial dysfunction, and oxidative stress, which are well known instances involved in the pathogenesis of neurodegenerative disorders, including Alzheimer disease (AD) [1]. Recent evidence suggests that hypometabolism might take place also in astrocytes, which can lose their normal neuroprotective capabilities and be engaged in neurological diseases by determining the progression and outcome of neuropathological process [2]. In this line, the aim of this study was to explore the potential role of astrocytes in driving a cascade of detrimental effects in neighboring neurons and to investigate a possible approach able to limit the injury in both cell types. Primary rat cortical astrocytes were subjected to glyceraldehyde (GA) to induce metabolic stress [3]. The study was conducted to examine whether damaged astrocytes could affect neuronal survival. In particular, cellular viability, ATP production, inflammatory state and oxidative stress were assessed in astrocytes treated with GA and glutamate (glut), used as an alternative substrate. Results indicated that GA exposure led to concentration-dependent astrocyte injury, activating the NF-kB pathway and increasing TNFα release and glutamate transporters expression levels which were mitigated by glut. Co-culturing injured astrocytes with neurons resulted in significant neuronal viability reduction. Conversely, glutamate exposure improved intracellular ATP levels and decreased AD markers in neurons.
The research indicates that astrocytes with metabolic issues may contribute to the damage of neighboring neurons in AD. This underscores the importance of exploring astrocyte-targeted therapies for potential neuroprotective interventions in future studies on AD.
1. Nat Rev Neurosci 2019 Mar;20(3):148-160.
2. Front Neurol. 2021; 12: 619626.
3. Cells. 2021 Aug 17;10(8):2109
Cracking the code of sodium/calcium exchanger (NCX) gating: old and new complexities surfacing from the deep web of secondary regulations
No full textCell membranes spatially define gradients that drive the complexity of biological signals. To guarantee movements and exchanges of solutes between compartments, membrane transporters negotiate the passages of ions and other important molecules through lipid bilayers. The Na+/Ca2+ exchangers (NCXs) in particular play central roles in balancing Na+ and Ca2+ fluxes across diverse proteolipid borders in all eukaryotic cells, influencing cellular functions and fate by multiple means. To prevent progression from balance to disease, redundant regulatory mechanisms cooperate at multiple levels (transcriptional, translational, and post-translational) and guarantee that the activities of NCXs are finely-tuned to cell homeostatic requirements. When this regulatory network is disturbed by pathological forces, cells may approach the end of life. In this review, we will discuss the main findings, controversies and open questions about regulatory mechanisms that control NCX functions in health and disease
A new K+channel-independent mechanism is involved in the antioxidant effect of XE-991 in an in vitro model of glucose metabolism impairment: implications for Alzheimer’s disease
Full text linkAlzheimer's disease (AD) is a neurodegenerative disorder that represents the first cause of dementia. Although there has been significant progress in AD research, the actual mechanisms underlying this pathology remain largely unknown. There is increasing evidence that oxidative stress, metabolic alterations, and mitochondrial dysfunction are key players in the development and worsening of AD. As a result, in the past few years, remarkable attempts have been made to develop neuroprotective strategies against the impairment of mitochondrial dynamics and cell redox status. In the present study, we reveal a novel antioxidant K+ channel-independent effect of the M-current inhibitor XE-991 in SH-SY5Y cells differentiated with retinoic acid (RA) and primary rat cortical neurons exposed to the glycolysis inhibitor glyceraldehyde (GA). This experimental approach aimed to create a condition of hypometabolism accompanied by mitochondrial dysfunction and redox imbalance, as frequently observed in the beginning stage of the disease. We found that XE-991 exerted a neuroprotective action most likely through the resumption of superoxide dismutase (SOD) activity, which was significantly compromised during GA challenge. We also observed that the enhancement of SOD activity was accompanied by a sequence of positive effects; these included the reduction in basal Ca2+ levels within cytoplasmic and mitochondrial compartments, the decrease in mitochondrial reactive oxygen species (ROS) production, the modulation of AMPK/mTOR pathway, the recovery of ΔΨm collapse, the increase in the intracellular ATP content and the decrease in amyloid-β (Aβ) and hyperphosphorylated form of tau protein (pTau) levels. Collectively, our study reveals an off-target antioxidant effect of XE-991 and paves the way toward the further evaluation of new therapeutic uses of already existing molecules to accelerate the process of developing an effective therapy to counteract AD
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
The Neuroprotective Effect of L-Carnitine against Glyceraldehyde-Induced Metabolic Impairment: Possible Implications in Alzheimer's Disease
No full textAlzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive regression and memory loss. Dysfunctions of both glucose metabolism and mitochondrial dynamics have been recognized as the main upstream events of the degenerative processes leading to AD. It has been recently found that correcting cell metabolism by providing alternative substrates can prevent neuronal injury by retaining mitochondrial function and reducing AD marker levels. Here, we induced an AD-like phenotype by using the glycolysis inhibitor glyceraldehyde (GA) and explored whether L-carnitine (4-N-trimethylamino-3-hydroxybutyric acid, LC) could mitigate neuronal damage, both in SH-SY5Y neuroblastoma cells and in rat primary cortical neurons. We have already reported that GA significantly modified AD marker levels; here we demonstrated that GA dramatically compromised cellular bioenergetic status, as revealed by glycolysis and oxygen consumption rate (OCR) evaluation. We found that LC ameliorated cell survival, improved OCR and ATP synthesis, prevented the loss of the mitochondrial membrane potential (Delta psi(m)) and reduced the formation of reactive oxygen species (ROS). Of note, the beneficial effect of LC did not rely on the glycolytic pathway rescue. Finally, we noticed that LC significantly reduced the increase in pTau levels induced by GA. Overall, these findings suggest that the use of LC can promote cell survival in the setting of the metabolic impairments commonly observed in AD. Our data suggest that LC may act by maintaining mitochondrial function and by reducing the pTau level
- …
