Posted in biotech/medical, neuroscience | Leave a Comment on Astrocyte-to-neuron H2O2 signalling supports long-term memory formation in Drosophila and is impaired in an Alzheimer’s disease model
Rabah et al. discover an astrocyte-to-neuron hydrogen peroxide signalling cascade, which is crucial for long-term memory formation in Drosophila. This signalling is found to be inhibited by amyloid-β peptide, suggesting a link to Alzheimer’s disease.
Mechanism of neuroinflammation protection by astrocytes.
How astrocytes controls neuroinflammation is not clearly understood.
The researchers demonstrate that the upregulation of basic leucine zipper ATF-like transcription factor (BATF)2 downstream of IFNg regulates the inflammatory potential of astrocytes during neuroinflammation.
In vivo evidence suggests that BATF2 limits CNS autoimmunity and the expression of IFNg-driven inflammatory mediators.
Mechanistically, BATF2 binds and prevents the overexpression of IFN regulatory factor (IRF)1 and IRF1 targets such as caspase-1. Batf2−/− mice exhibit exacerbated clinical disease severity in a murine model of central nervous system autoimmunity and express increased astrocyte-specific IRF1 and caspase-1, suggesting an amplified IFN response in vivo.
They also demonstrate that BATF2 expressed primarily in astrocytes within multiple sclerosis lesions and that this expression is colocalized with IRF1.
These data suggest that BATF2 contributes to protective mechanisms in astrocytes during chronic neuroinflammation. https://sciencemission.com/BATF2-and-neuroinflammation
Here Harkos et al. review the role of continuous models and discrete models in predicting and understanding therapy delivery and efficacy in solid tumours. They propose ways to integrate mechanistic and AI-based models to further improve patient outcomes.
Results of a trial revealed that a unique investigational drug formulation called Rhenium Obisbemeda (186RNL) more than doubled median survival and progression-free time, compared with standard median survival and progression rates, and with no dose-limiting toxic effects.
Rhenium Obisbemeda enables very high levels of a specific activity of rhenium-186 (186Re), a beta-emitting radioisotope, to be delivered by tiny liposomes, referring to artificial vesicles or sacs having at least one lipid bilayer. The researchers used a custom molecule known as BMEDA to chelate or attach 186Re and transport it into the interior of a liposome where it is irreversibly trapped.
In this trial, known as the phase 1 ReSPECT-GBM trial, scientists set out to determine the maximum tolerated dose of the drug, as well as safety, overall response rate, disease progression-free survival and overall survival.
After failing one to three therapies, 21 patients who were enrolled in the study between March 5, 2015, and April 22, 2021, were treated with the drug administered directly to the tumors using neuronavigation and convection catheters.
The researchers observed a significant improvement in survival compared with historical controls, especially in patients with the highest absorbed doses, with a median survival and progression-free time of 17 months and 6 months, respectively, for doses greater than 100 gray (Gy), referring to units of radiation.
Importantly, they did not observe any dose-limiting toxic effects, with most adverse effects deemed unrelated to the study treatment.
Northwestern Medicine investigators have uncovered new insights into how intercellular “glue” functions to enable interactions between cells, as detailed in a study published in Nature Communications.
In order to communicate and transfer cellular cargo, cells within tissues can link together by fusing their cytoskeletons and cell membranes.
These connective structures, called adherens junctions, play important roles in tissue development and renewal, but remain poorly understood, said Sergey Troyanovsky, Ph.D., professor of Dermatology, of Cell and Developmental Biology and senior author of the study.
What makes us unique? Different from most, yet similar to a few? What shapes our physical, behavioral, and even mental makeup? The answer lies in our genes.
Passed from parents to their offspring, genes contain the information that specifies physical and biological traits.
But that’s not all. Genes are also responsible for diseases. Faulty genes can cause all kinds of issues that can manifest as birth defects, chronic diseases, or developmental problems.
Mitochondria are the powerhouses in our cells, producing the energy for all vital processes. Using cryo-electron tomography, researchers at the University of Basel, Switzerland, have now gained insight into the architecture of mitochondria at unprecedented resolution.
The results of the study are published in Science.
They discovered that the proteins responsible for energy generation assemble into large “supercomplexes,” which play a crucial role in providing the cell’s energy.
Researchers have discovered that Daphne pseudomezereum (commonly known as Onishibari) contains a substance inhibiting replication of human immunodeficiency virus (HIV). The plants were cultivated at the Medicinal Plant Garden of the Faculty of Pharmaceutical Sciences, Toho University. This finding is expected to lead to the discovery of drug seeds for novel drugs with superior anti-HIV activity.
A paper reporting this study was published in the journal Phytochemistry. The research group was led by Professor Wei Li from the Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Toho University, in collaboration with the Duke University Medical Center in the United States.
The Thymelaeaceae family consists of over 53 genera and 800 species distributed worldwide, except in polar and desert regions. These plants contain diterpenoids, which exhibit significant biological activities, including anticancer, anti-HIV, and analgesic effects.
A new study by UCLA Health has discovered what researchers say is the first drug to fully reproduce the effects of physical stroke rehabilitation in model mice, following from human studies.
The findings, published in Nature Communications, tested two candidate drugs derived from their studies on the mechanism of the brain effects of rehabilitation, of which one resulted in significant recovery in movement control after stroke in the mouse model.
Stroke is the leading cause of adult disability because most patients do not fully recover from the effects of stroke. There are no drugs in the field of stroke recovery, requiring stroke patients to undergo physical rehabilitation which has shown to be only modestly effective.
Memory engrams are formed through experience-dependent plasticity of neural circuits, but their detailed architectures remain unresolved. Using three-dimensional electron microscopy, we performed nanoscale reconstructions of the hippocampal CA3-CA1 pathway after chemogenetic labeling of cellular ensembles recruited during associative learning. Neurons with a remote history of activity coinciding with memory acquisition showed no strong preference for wiring with each other. Instead, their connectomes expanded through multisynaptic boutons independently of the coactivation state of postsynaptic partners. The rewiring of ensembles representing an initial engram was accompanied by input-specific, spatially restricted upscaling of individual synapses, as well as remodeling of mitochondria, smooth endoplasmic reticulum, and interactions with astrocytes.