To investigate the role of oxidative stress and/or mitochondrial impairment in the occurrence of acute kidney injury (AKI) during sepsis, we developed a sepsis-induced in vitro model using proximal ...tubular epithelial cells exposed to a bacterial endotoxin (lipopolysaccharide, LPS). This investigation has provided key features on the relationship between oxidative stress and mitochondrial respiratory chain activity defects.
LPS treatment resulted in an increase in the expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase 4 (NOX-4), suggesting the cytosolic overexpression of nitric oxide and superoxide anion, the primary reactive nitrogen species (RNS) and reactive oxygen species (ROS). This oxidant state seemed to interrupt mitochondrial oxidative phosphorylation by reducing cytochrome c oxidase activity. As a consequence, disruptions in the electron transport and the proton pumping across the mitochondrial inner membrane occurred, leading to a decrease of the mitochondrial membrane potential, a release of apoptotic-inducing factors and a depletion of adenosine triphosphate. Interestingly, after being targeted by RNS and ROS, mitochondria became in turn producer of ROS, thus contributing to increase the mitochondrial dysfunction.
The role of oxidants in mitochondrial dysfunction was further confirmed by the use of iNOS inhibitors or antioxidants that preserve cytochrome c oxidase activity and prevent mitochondrial membrane potential dissipation. These results suggest that sepsis-induced AKI should not only be regarded as failure of energy status but also as an integrated response, including transcriptional events, ROS signaling, mitochondrial activity and metabolic orientation such as apoptosis.
•Mitochondrial respiratory chain dysfunction is a key player in sepsis-induced AKI.•NADPH oxidase-derived O2− production participates in the cytosolic oxidative•stress.•NO and ONOO- are important mediators in the LPS-induced mitochondrial•impairment.•LPS stress reduces cytochrome c oxidase activity and ATP production.•After being targeted by ROS, mitochondria became producer of ROS.
While the effects of rewards on memory appear well documented, the effects of punishments remain uncertain. Based on neuroimaging data, this study tested the hypothesis that, as compared to a neutral ...condition, a context allowing successful punishment avoidance would enhance memory to a similar extent as rewards. In a fully within-subject and counter-balanced design, participants (n = 18) took part in 3 distinct learning sessions during which the delivery of performance-contingent monetary punishments and rewards was manipulated. Specifically, participants had to reach towards visual targets while compensating for a gradually introduced visual deviation. Accuracy at achieving targets was either punished (Hit: “+0$”; Miss: “−0.5$), rewarded (Hit: “+0.5$”; Miss: “−0$”), or associated with neutral binary feedback (Hit: “Hit”; Miss: “Miss”). Retention was assessed through reach aftereffects both immediately and 24 h after initial acquisition. The results disconfirmed the hypothesis by showing that the punishment and reward learning sessions both impaired retention as compared to the neutral session, suggesting that both types of incentives similarly impaired memory formation and consolidation. Two alternative but complementary interpretations are discussed. One interpretation is that the presence of punishments and rewards induced a negative learning context, which – based on neurobiological data – could have been sufficient to interfere with memory formation and consolidation. Another interpretation is that punishments and rewards emphasized the disrupting effects of target hits on implicit learning processes, therefore yielding retention impairments. Altogether, these results suggest that incentives can have counter-productive effects on memory.
Anterograde interference emerges when
are learned in close temporal proximity, an effect repeatedly attributed to a competition between differing task memories. However, recent development ...alternatively suggests that initial learning may trigger a refractory period that occludes neuroplasticity and impairs subsequent learning, consequently mediating interference independently of memory competition. Accordingly, this study tested the hypothesis that interference can emerge when
that is when competition between memories is prevented. In a first experiment, the inter-session interval (ISI) between two identical motor learning sessions was manipulated to be 2 min, 1 h or 24 h. Results revealed that retention of the second session was impaired as compared to the first one when the ISI was 2 min but not when it was 1 h or 24 h, indicating a time-dependent process. Results from a second experiment replicated those of the first one and revealed that adding a third motor learning session with a 2 min ISI further impaired retention, indicating a dose-dependent process. Results from a third experiment revealed that the retention impairments did not take place when a learning session was preceded by simple rehearsal of the motor task without concurrent learning, thus ruling out fatigue and confirming that retention is impaired specifically when preceded by a learning session. Altogether, the present results suggest that competing memories is not the sole mechanism mediating anterograde interference and introduce the possibility that a time- and dose-dependent refractory period-independent of fatigue-also contributes to its emergence. One possibility is that learning transiently perturbs the homeostasis of learning-related neuronal substrates. Introducing additional learning when homeostasis is still perturbed may not only impair performance improvements, but also memory formation.
Classically interpreted as a competition between opposite memories (A vs B), anterograde interference (AI) also emerges in the absence of competing memories (A vs A), suggesting that mechanisms other ...than those involved in memory competition contribute to AI. To investigate this, we tested the hypothesis that extending motor practice would enhance a first memory, but come at the cost of reduced learning capabilities when subsequently exposed to a second learning session of the same task. Based on converging biological evidence, AI was expected to depend upon the degree of extended practice of the initial exposure. During a first Session, four conditions were carried out where participants (n = 24) adapted to a gradually introduced -20° visual deviation while the extent of the initial exposure was manipulated by varying the duration or type of the performance asymptote. Specifically, the performance asymptote at -20° was either Short (40 trials), Moderate (160 trials), Long (320 trials), or absent due to continuously changing perturbations around the mean of -20° (Jagged; 160 trials). After a 2-min interval, participants re-adapted to the same (-20°) visual deviation, which was meant to probe the effect of extended practice in the first Session on the learning capabilities of a second identical memory (A vs A). The results first confirmed that the duration of exposure in the first Session enhanced immediate aftereffects in the Moderate, Long, and Jagged conditions as compared to the Short condition, suggesting that extended practice enhanced retention of the first memory. When comparing the second Session to the first one, results revealed a different pattern of re-adaptation depending on the duration of initial exposure: in the Short condition, there was evidence for facilitated re-adaptation and similar aftereffects. However, in the Moderate, Long and Jagged conditions, re-adaptation was similar and aftereffects were impaired, suggestive of AI. This suggests that extended practice initially enhances memory formation, but comes at the cost of reduced subsequent learning capabilities. One possibility is that AI occurs because extended practice induces the emergence of network-specific homeostatic constraints, which limit subsequent neuroplastic and learning capabilities in the same neural network.
The anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1) plays an important role in survival and differentiation of leukocytes, more specifically of neutrophils. Here, we investigated the impact of ...myeloid Mcl-1 deletion in atherosclerosis. Western type diet fed LDL receptor-deficient mice were transplanted with either wild-type (WT) or LysMCre Mcl-1
(Mcl-1
) bone marrow. Mcl-1 myeloid deletion resulted in enhanced apoptosis and lipid accumulation in atherosclerotic plaques. In vitro, Mcl-1 deficient macrophages also showed increased lipid accumulation, resulting in increased sensitivity to lipid-induced cell death. However, plaque size, necrotic core and macrophage content were similar in Mcl-1
compared to WT mice, most likely due to decreased circulating and plaque-residing neutrophils. Interestingly, Mcl-1
peritoneal foam cells formed up to 45% more multinucleated giant cells (MGCs) in vitro compared to WT, which concurred with an increased MGC presence in atherosclerotic lesions of Mcl-1
mice. Moreover, analysis of human unstable atherosclerotic lesions also revealed a significant inverse correlation between MGC lesion content and Mcl-1 gene expression, coinciding with the mouse data. Taken together, these findings suggest that myeloid Mcl-1 deletion leads to a more apoptotic, lipid and MGC-enriched phenotype. These potentially pro-atherogenic effects are however counteracted by neutropenia in circulation and plaque.
Repeated application of organic fertiliser has unintentionally let to the introduction into surface water and soils of many phytotoxic substances that compromise agricultural production and threaten ...environmental quality. Recent studies using hydroponic systems have reported that bisphenol A (BPA) affects essential mineral elements contents and root absorptive function, thereby impacting nutrient content in plant. However, in soils, plants develop specific traits related to nutrient acquisition strategies. In order to ensure optimised supply of nutrients, understanding the response of these traits under BPA stress is thus essential. Here, we therefore, investigated how leaf nutrient contents (P, Ca and K), root morphology, P-mobilising exudates and rhizospheric microbiota biomass respond to BPA soil contamination using wheat (
Triticum aestivum
) as plant model. After 7 weeks, root and leaf traits were not markedly affected by the exposure to BPA at low and high concentrations (0.1 and 1000 mg kg
−1
soil). Significant change on average root diameter and aerial biomass were only observed at the highest dose. BPA contamination had no influence on nutrients acquisition traits and root-associated microbiota. Specific root length, carboxylates exudation and P, Ca and K concentrations in leafs were similar irrespective of the treatments. In addition, total microbial biomass, bacteria and fungi abundance measured through phospholipid fatty acid analysis did not differ among controls and contaminated soils. In summary, this experiment suggests a limited influence of BPA contaminated soils on traits involved in nutrient acquisition in wheat.
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