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Category: biotech/medical – Page 6

Cellular and molecular mechanisms of astrocyte plasticity in learning and memory

Astrocyte plasticity in learning and memory.

Neuronal hallmark features of learning and memory, such as activity dependent plasticity, circuit-level modulation, and gene regulatory mechanisms, are also observed in astrocytes.

Astrocytic calcium displays plastic, activity-dependent recruitment and refinement (akin to neuronal activity) across neuronal subtypes, brain regions, and behavioral paradigms, and Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)-mediated manipulations highlight astrocytic recruitment of circuit-specific neurons.

Astrocyte peripheral processes display activity-dependent plasticity and are able to discriminate between neuronal subtypes, circuits, and even individual synapses.

Single-cell RNA sequencing reveals molecularly defined subtypes of astrocytes that display unique transcriptional responses to learning and memory and implicates potential ‘ensemble’-like networks of astrocytes. sciencenewshighlights ScienceMission https://sciencemission.com/astrocyte-plasticity

Learning and memory arise from coordinated activity-dependent plasticity across neural circuits and brain regions. Astrocytes are increasingly recognized as active contributors to learning and memory via their roles in sensing, integrating, and responding to contextual information. Astrocytes modulate synaptic transmission, engage in circuit-specific signaling, and display context-dependent calcium dynamics that influence behavior. In this review, we focus on astrocyte functions across rodent models that display plasticity traditionally ascribed to neurons, including activity-dependent molecular and structural plasticity, circuit-level modulation, ensemble-like networks, and transcriptional, translational, proteomic, and epigenetic plasticity.

Continue reading “Cellular and molecular mechanisms of astrocyte plasticity in learning and memory” | >

First-in-class molecules dial down inflammation without compromising immunity

Scripps Research scientists have developed a new class of drug compounds that reduce harmful inflammation while leaving the body’s ability to fight infections intact—a long-sought goal in treating autoimmune diseases. The compounds, called ENDOtollins, work by interrupting a “molecular handshake” between two proteins inside immune cells. The research, published in Nature Chemical Biology, could lead to more targeted treatments for conditions like lupus, rheumatoid arthritis and juvenile arthritis, which together affect more than 15 million Americans.

“A key component of our approach is to begin by understanding the biological mechanisms at play,” says Sergio D. Catz, professor at Scripps Research and senior author. “By accomplishing this first, we can more easily target the pathway driving inflammation without affecting other important processes.”

New Alzheimer’s Treatment Strategy Reverses Cognitive Decline in Mice

Researchers have developed a novel compound that could transform the way we treat Alzheimer’s disease, offering not just a new weapon but potentially a new strategy for battling the most common form of dementia worldwide.

While current drugs for Alzheimer’s mostly focus on removing amyloid-beta plaques associated with the disease, the new compound takes a fundamentally different approach, instead targeting a specific enzyme to therapeutically reprogram the epigenome of neurons – a series of molecular marks that can be added to or removed from DNA, to change the way genes work.

Monoclonal antibody drugs such as lecanemab and donanemab, which target amyloid-beta proteins, help somewhat to slow the progression of the disease when treatment is started early, but there is still no proven way to reverse cognitive decline from Alzheimer’s in humans.

Ganglion Cell Layer Compared With Inner Plexiform Layer Atrophy After Optic Neuritis Associated With NMOSD, MOGAD, and MS

In a phase 3 randomized clinical trial of adults with ParkinsonDisease experiencing motor fluctuations despite stable levodopa therapy, adjunctive tavapadon—a once-daily, selective D1/D5 dopamine agonist—significantly increased daily on-time without troublesome dyskinesia and reduced off-time compared with placebo over 27 weeks.

Most adverse events, including nausea, dyskinesia, and dizziness, were mild to moderate. Tavapadon showed a favorable safety profile and provided clinically meaningful motor improvements as adjunctive therapy.

Question Can adjunctive tavapadon—an oral, once-daily, selective dopamine (D) D1/D5 agonist—improve motor control for people with Parkinson disease (PD) experiencing motor fluctuations while minimizing risk of adverse events?

Findings In this phase 3, double-blind, placebo-controlled, 27-week randomized clinical trial of 507 participants with PD, tavapadon significantly increased daily on-time without troublesome dyskinesia (good-on-time) vs placebo. Most adverse events were mild to moderate in severity with nausea, dyskinesia, and dizziness most common with tavapadon.

Meaning Results show that tavapadon adjunctive to levodopa provided clinically meaningful motor improvements and an acceptable safety profile in adults with PD experiencing motor fluctuations while receiving oral levodopa.

New genetic risk score better predicts diabetes, obesity and downstream complications

Type 2 diabetes (T2D) and obesity are metabolic conditions with many causes, including overlapping and distinct genetic features. A polygenic risk score (PRS) can capture multiple genetic risk factors to provide an estimate for whether a person may develop a complex medical condition and how they might fare long-term.

Building stronger genetic risk scores By integrating genetic findings from several of the world’s largest biobanks, investigators from Mass General Brigham built metabolic PRSs for predicting obesity and T2D, which outperformed existing disease-prediction models and predicted downstream morbidity and clinical interventions. Findings are published in Cell Metabolism.

“Our intention was to not only capture the risk of being diagnosed with obesity or diabetes, but also to better predict health consequences across the life course by integrating many aspects of metabolic function,” said co-first author Min Seo Kim, MD, MSc.

Designed to remember

In a new Science study, researchers report that specific regions dense in cytosine and guanosine dinucleotides are epigenetically modified during inflammation to enable gene expression and that these changes persist during the animal’s lifetime.

The finding has implications for understanding how the genome determines the longevity of memory, which affects tissue fitness.

Learn more in a new Science Perspective.

Specific DNA sequence features encode the persistence of epigenetic memory of inflammation.

Guillaume Blot and Przemyslaw Sapieha Authors Info & Affiliations

Science

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How stimulating the vagus nerve could protect the brain from Alzheimer’s disease

Developing tau tangles doesn’t mean a person has Alzheimer’s disease – in fact, it happens to nearly everyone to varying degrees. But because these changes start in the locus coeruleus, some brain researchers – myself included – see this area as a canary in the coal mine for developing Alzheimer’s disease.

We are exploring whether stopping or slowing down tau tangles in this brain region, or otherwise maintaining its health, may be a way to interrupt how the disease ultimately unfolds and to prevent other aspects of cognitive aging.

Emerging research from my lab and others is investigating the idea that a therapy called vagus nerve stimulation, which is already widely used for other health conditions, could be one way of keeping the locus coeruleus functioning properly.

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