Brain-derived neurotrophic factor (BDNF) belongs to a family of small secreted proteins that also include nerve growth factor, neurotrophin 3, and neurotrophin 4. BDNF stands out among all ...neurotrophins by its high expression levels in the brain and its potent effects at synapses. Several aspects of BDNF biology such as transcription, processing, and secretion are regulated by synaptic activity. Such observations prompted the suggestion that BDNF may regulate activity-dependent forms of synaptic plasticity such as long-term potentiation (LTP), a sustained enhancement of excitatory synaptic efficacy thought to underlie learning and memory. Here, we will review the evidence pointing to a fundamental role of this neurotrophin in LTP, especially within the hippocampus. Prominent questions in the field, including the release and action sites of BDNF during LTP, as well as the signaling and molecular mechanisms involved, will also be addressed. The diverse effects of BDNF at excitatory synapses are determined by the activation of TrkB receptors and downstream signaling pathways, and the functions, typically opposing in nature, of its immature form (proBDNF). The activation of p75
receptors by proBDNF and the implications for long-term depression will also be addressed. Finally, we discuss the synergy between TrkB and glucocorticoid receptor signaling to determine cellular responses to stress.
Abstract
Inflammatory states and body composition changes are associated with a poor prognosis in many diseases, but their role in coronavirus disease 2019 (COVID-19) is not fully understood. To ...assess the impact of low skeletal muscle radiodensity (SMD), high neutrophil-to-lymphocyte ratio (NLR) and a composite score based on both variables, on complications, use of ventilatory support, and survival in patients with COVID-19. Medical records of patients hospitalized between May 1, 2020, and July 31, 2020, with a laboratory diagnosis of COVID-19 who underwent computed tomography (CT) were retrospectively reviewed. CT-derived body composition measurements assessed at the first lumbar vertebra level, and laboratory tests performed at diagnosis, were used to calculate SMD and NLR. Prognostic values were estimated via univariate and multivariate logistic regression analyses and the Kaplan–Meier curve. The study was approved by the local Institutional Review Board (CAAE 36276620.2.0000.5404). A total of 200 patients were included. Among the patients assessed, median age was 59 years, 58% were men and 45% required ICU care. A total of 45 (22.5%) patients died. Multivariate logistic analysis demonstrated that a low SMD (OR 2.94; 95% CI 1.13–7.66,
P
= 0.027), high NLR (OR 3.96; 95% CI 1.24–12.69,
P
= 0.021) and both low SMD and high NLR (OR 25.58; 95% CI 2.37–276.71,
P
= 0.008) combined, were associated with an increased risk of death. Patients who had both low SMD and high NLR required more mechanical ventilation (
P
< 0.001) and were hospitalized for a longer period (
P
< 0.001). Low SMD, high NLR and the composite score can predict poor prognosis in patients with COVID-19, and can be used as a tool for early identification of patients at risk. Systemic inflammation and low muscle radiodensity are useful predictors of poor prognosis, and the assessment of these factors in clinical practice should be considered.
Neurotrophins protect neurons against glutamate excitotoxicity, but the signaling mechanisms have not been fully elucidated. We studied the role of the phosphatidylinositol 3-kinase (PI3-K) and ...Ras/mitogen-activated protein kinase (MAPK) pathways in the protection of cultured hippocampal neurons from glutamate induced apoptotic cell death, characterized by nuclear condensation and activation of caspase-3-like enzymes. Pre-incubation with the neurotrophin brain-derived neurotrophic factor (BDNF), for 24 h, reduced glutamate-evoked apoptotic morphology and caspase-3-like activity, and transiently increased the activity of the PI3-K and of the Ras/MAPK pathways. Inhibition of the PI3-K and of the Ras/MAPK signaling pathways abrogated the protective effect of BDNF against glutamate-induced neuronal death and similar effects were observed upon inhibition of protein synthesis. Moreover, incubation of hippocampal neurons with BDNF, for 24 h, increased Bcl-2 protein levels. The results indicate that the protective effect of BDNF in hippocampal neurons against glutamate toxicity is mediated by the PI3-K and the Ras/MAPK signaling pathways, and involves a long-term change in protein synthesis.
Aim
To evaluate the radiopacity, setting time, pH level, calcium ion release and solubility of white mineral trioxide aggregate (MTA; Angelus, Londrina, Pr, Brazil) with different powder‐to‐water ...ratios.
Methodology
Three MTA groups were prepared using 4 : 1, 3 : 1 and 2 : 1 powder‐to‐water ratios. For the radiopacity analysis, the 10 × 1 mm specimens were arranged on occlusal films with a cylinder of dentine and an aluminium stepwedge. The digitized radiographs were evaluated with Digora 1.51 software to determine the radiographic density. The setting time test was performed according to the American Society for Testing and Materials 266/08 standard specifications, but the specimens were made according to International Organization for Standardization 6876:2001. Thirty acrylic teeth with root‐end filling material were immersed in ultrapure water for measurement of pH level and calcium ion release (atomic absorption spectrophotometer) at 3, 24, 72 and 168 h. In the solubility test, the root‐end fillings of 30 acrylic teeth were scanned twice by a Micro‐CT, before and after immersion in ultrapure water for 168 h. Digital data were reconstructed, and the volume (mm3) of the samples was obtained using CTan software (CTan v1.11.10.0, SkyScan). The data were statistically analysed by the anova, Tukey, Kruskal–Wallis and Dunn's tests.
Results
The radiopacity was higher (P < 0.05) when the 4 : 1 proportion was utilized. The setting time was longer, and the pH level and calcium ion release were higher (P < 0.05) with a greater volume of water. The group with more water (2 : 1) had significantly (P < 0.05) more material volume loss (6.46%) compared with the other groups.
Conclusions
The ratio of powder/water significantly interfered with the physical and chemical properties of white MTA Angelus.
Abstract In neurological disorders, both acute and chronic neural stress can disrupt cellular proteostasis, resulting in the generation of pathological protein. However in most cases, neurons adapt ...to these proteostatic perturbations by activating a range of cellular protective and repair responses, thus maintaining cell function. These interconnected adaptive mechanisms comprise a ‘proteostasis network’ and include the unfolded protein response, the ubiquitin proteasome system and autophagy. Interestingly, several recent studies have shown that these adaptive responses can be stimulated by preconditioning treatments, which confer resistance to a subsequent toxic challenge – the phenomenon known as hormesis. In this review we discuss the impact of adaptive stress responses stimulated in diverse human neuropathologies including Parkinson׳s disease, Wolfram syndrome, brain ischemia, and brain cancer. Further, we examine how these responses and the molecular pathways they recruit might be exploited for therapeutic gain. This article is part of a Special Issue entitled SI:ER stress.
Abstract Global cerebral ischemia induces selective acute neuronal injury of the CA1 region of the hippocampus. The type of cell death that ensues may include different programmed cell death ...mechanisms namely apoptosis and necroptosis, a recently described type of programmed necrosis. We investigated whether necroptosis contributes to hippocampal neuronal death following oxygen-glucose deprivation (OGD), an in vitro model of global ischemia. We observed that OGD induced a death receptor (DR)-dependent component of necroptotic cell death in primary cultures of hippocampal neurons. Additionally, we found that this ischemic challenge upregulated the receptor-interacting protein kinase 3 (RIP3) mRNA and protein levels, with a concomitant increase of the RIP1 protein. Together, these two related proteins form the necrosome, the complex responsible for induction of necroptotic cell death. Interestingly, we found that caspase-8 mRNA, a known negative regulator of necroptosis, was transiently decreased following OGD. Importantly, we observed that the OGD-induced increase in the RIP3 protein was paralleled in an in vivo model of transient global cerebral ischemia, specifically in the CA1 area of the hippocampus. Moreover, we show that the induction of endogenous RIP3 protein levels influenced neuronal toxicity since we found that RIP3 knock-down (KD) abrogated the component of OGD-induced necrotic neuronal death while RIP3 overexpression exacerbated neuronal death following OGD. Overexpression of RIP1 also had deleterious effects following the OGD challenge. Taken together, our results highlight that cerebral ischemia activates transcriptional changes that lead to an increase in the endogenous RIP3 protein level which might contribute to the formation of the necrosome complex and to the subsequent component of necroptotic neuronal death that follows ischemic injury.
Aim
To use micro‐CT to quantitatively evaluate the amount of residual filling material after using several techniques to remove root fillings with and without ultrasonic activation and to analyse the ...cleanliness of the root canal walls and dentine tubules with scanning electron microscopy (SEM).
Methodology
The root canals of one hundred and eight human mandibular incisors were selected and instrumented with rotary files using the BioRace system up to file size 40, .04 taper. After instrumentation, the teeth were filled using a hybrid technique with gutta‐percha and sealer then divided into three groups according to the method used for removing the root filling: G1‐Reciproc (using only instrument R50), G2‐ProTaper Universal retreatment system and G3‐Manual (hand files and Gates‐Glidden burs). All groups were divided into two subgroups depending on whether ultrasonic agitation was used with the irrigants. Micro‐CT scans were taken before and after removal of the filling material to detect residual material in the canal. After micro‐CT analysis, the roots were cut in half, imaged by SEM and scored based on the amount of surface covered by root filling remnants. The data were analysed statistically using a significance level of 5%.
Results
All groups had retained material in the root canals after instrumentation. The Reciproc method was associated with less retained material than the ProTaper and Manual methods. Ultrasonic activation significantly reduced the amount of residual root filling in all groups (P < 0.05).
Conclusion
None of the instrumentation methods were able to completely remove root filling material. Ultrasonic activation improved the removal of root filling material in all groups.
•There is an asymmetrical reorganization of the motor cortex in patients with phantom limb pain.•We found disorganized and shifted hand cortical representation in the affected hemisphere.•This ...reorganization is not associated with pain intensity.
The role of motor cortex reorganization in the development and maintenance of phantom limb pain (PLP) is still unclear. This study aims to evaluate neurophysiological and structural motor cortex asymmetry in patients with PLP and its relationship with pain intensity.
Cross-sectional analysis of an ongoing randomized-controlled trial. We evaluated the motor cortex asymmetry through two techniques: i) changes in cortical excitability indexed by transcranial magnetic stimulation (motor evoked potential, paired-pulse paradigms and cortical mapping), and ii) voxel-wise grey matter asymmetry analysis by brain magnetic resonance imaging.
We included 62 unilateral traumatic lower limb amputees with a mean PLP of 5.9 (SD = 1.79). We found, in the affected hemisphere, an anterior shift of the hand area center of gravity (23 mm, 95% CI 6 to 38, p = 0.005) and a disorganized and widespread representation. Regarding voxel-wise grey matter asymmetry analysis, data from 21 participants show a loss of grey matter volume in the motor area of the affected hemisphere. This asymmetry seems negatively associated with time since amputation. For TMS data, only the ICF ratio is negatively correlated with PLP intensity (r = −0.25, p = 0.04).
There is an asymmetrical reorganization of the motor cortex in patients with PLP, characterized by a disorganized, widespread, and shifted hand cortical representation and a loss in grey matter volume in the affected hemisphere. This reorganization seems to reduce across time since amputation. However, it is not associated with pain intensity.
These findings are significant to understand the role of the motor cortex reorganization in patients with PLP, showing that the pain intensity may be related with other neurophysiological factors, not just cortical reorganization.
In order to take advantage of the high affinity between mercury and sulphur, magnetite (Fe
3O
4) particles functionalized with dithiocarbamate groups (
CS
2
−
), were synthesized to be used as a new ...type of sorbent to remove Hg (II) from synthetic and natural spiked waters. The effectiveness of this type of sorbent was studied, and its potential as cleanup agent for contaminated waters was assessed.
Batch stirred tank experiments were carried out by contacting a volume of solution with known amounts of functionalized Fe
3O
4 particles, in order to study the effect of sorbent dose, salinity, and the kinetics and the equilibrium of this unit operation. A complete Hg (II) removal (
ca. 99.8%) was attained with 6 mg/L of magnetic particles for an initial metal concentration of 50 μg/L. It was confirmed that highly complex matrices, such as seawater (
ca. 99%) and river water (
ca. 97%), do not affect the removal capacity of the functionalized magnetic particles. Concerning isotherms, no significant differences were observed between two- and three-parameter models (
P = 0.05%); however, Sips isotherm provided the lowest values of SS and
S
x/y
, predicting a maximum sorption capacity of 206 mg/g, in the range of experimental conditions under study. The solid loadings measured in this essay surmount the majority of the values found in literature for other type of sorbents.
Display omitted
► Magnetic particles functionalized with dithiocarbamate groups as sorbents for Hg. ► High removal efficiency in natural waters. ► Increasing matrices’ complexity will not decrease particles efficiency. ► Easy removal of sorbent from solution due to the magnetite ferrimagnetic properties.
Protein quality has an important role in increasing satiety. Evidence suggests that whey protein (WP) provides satiety via gastrointestinal hormone secretion. Hydrolysed collagen supplementation can ...also stimulate the production of incretins and influence satiety and food intake. Thus, we sought to compare the effect of acute supplementation of WP or hydrolysed collagen on post-intervention appetite and energy consumption. This was a randomised, double-blind, crossover pilot study with ten healthy adult women (22·4 years/old) who were submitted to acute intake (single dose) of a beverage containing WP (40 g of concentrated WP) or hydrolysed collagen (40 g). Subjective appetite ratings (feelings of hunger, desire to eat and full stomach) were measured using the Visual Analog Scale (VAS), energy intake was quantified by
cheese bread consumption 2 hours after supplementation and blood was collected for leptin and glucose determination. There was no difference between treatment groups in the perception of hunger (
= 0·983), desire to eat (
= 0·326), full stomach feeling (
= 0·567) or food consumption (
= 0·168). Leptin concentrations at 60 min post supplementation were higher when subjects received hydrolysed collagen (
= 0·006). Acute supplementation with hydrolysed collagen increased leptin levels in comparison with WP, but had no effect on appetite measured by feelings of hunger, desire to eat, full stomach feeling (VAS) or energy consumption.
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