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Category: neuroscience – Page 9

Engineered protein markers read living brain gene activity in monkeys via blood

Gene therapy has been successfully used to treat a number of diseases, including immune deficiencies, hereditary blindness, hemophilia and, recently, Huntington’s disease, a fatal neurological disorder.

An advance reported in the journal Neuron adds to the technique’s growing track record of evidence supporting the view that it could unlock powerful, personalized therapies: Rice University bioengineer Jerzy Szablowski and collaborators in Vincent Costa’s lab at Emory University found that released markers of activity (RMAs) — engineered proteins designed to cross the blood-brain barrier and persist in the blood for hours at a time, providing a reliable and noninvasive way to get information about gene expression in the brain — work just as well in monkeys as they do in mice.

On the route from laboratory discovery to lifesaving treatment, large animal model studies are a critical part of the process. Most research never reaches this stage.

Bioengineered neuronal ‘circuit board’ mimics conditions of the human brain

A new bioengineered neuronal circuit board “BioConNet” allows scientists to artificially engineer human brain-like wiring at scale and can be used to engineer any possible circuit. The fully programmable, open-source system allows generation of large-scale circuits, while maintaining the ability to focus on single connections between neurons.

This is a key advance in engineering human-like neural circuits as it allows for a new level of wiring complexity compared to previous systems. BioConNet allows scientists increased control over wiring in the culture compared to existing methods such as organoids and commercially available systems. The research is published in the journal Advanced Healthcare Materials.

“By combining engineering and neurobiology with the most recent stem cell culture techniques, we can now create human-specific, functional, large-scale complex neural circuits in the lab,” said senior author, Dr. Andrea Serio, Reader in Neural Tissue Engineering, Group Leader at the UK Dementia Research Institute (UK DRI) at King’s and Senior Group Leader at the Crick.

High-Pressure Freezing EM Tomography of Entire Ribbon Synapses in the Retina

JNeurosci: Using advanced electron microscopy in rats, Zhang et al. captured 3D images of chemical synapses that perform visual computations in the retina. Their findings reveal how neural connections are structured for efficient visual signaling.

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In the retina, presynaptic active zones in photoreceptors and bipolar cells are distinguished by a plate-like “ribbon” linked to the plasma membrane (PM) and surrounded by dozens of synaptic vesicles (SVs) tethered to it. SVs at the base of the ribbon, closest to the PM, are thought to constitute the readily releasable vesicle pool (RRP), i.e., SVs primed to be released 1–2 ms following stimulation. The number of SVs in the RRP is a critical synaptic parameter that influences synaptic strength and varies with light levels to enable ribbon synapses to compute visual information. Physiological RRP measurements agree well with anatomical estimates obtained via electron microscopy (EM), although EM often employs chemical fixation, which causes exocytotic artifacts that may influence RRP size.

Adherence to Different Dietary Patterns and Subsequent Risk of Total, Ischemic, and Hemorrhagic Stroke

In people with elevated cardiovascular risk at baseline, adherence to the Mediterranean and Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diets was associated with a lower risk of stroke.

BACKGROUND: Adherence to healthy dietary patterns has been related to lower cardiovascular disease risk. However, few studies have examined prospective associations between adherence to different healthy dietary scores and the incidence of stroke and its subtypes. The aim of this study was to prospectively examine the associations between adherence to 4 recognized healthy dietary patterns and the risk of total and ischemic stroke in an existing dietary-based randomized controlled trial. METHODS: This is a secondary observational cohort analysis of 7,447 participants at high cardiovascular disease risk enrolled in the PREDIMED trial (Prevención Con Dieta Mediterranea).

What Can 50-Year-Old Chatbots Teach Us About Clinical Applications of AI?

Can a large language model (LLM) provide insights on the history of chatbots and their clinical applications? 🤖

In this episode of JAMA+ AI Conversations, JAMA+ AI Editor in Chief Roy Perlis, MD, MSc, interviews OpenAI’s ChatGPT (GPT-4o, voice mode) about the development and legacy of the first clinical chatbots, ELIZA and PARRY.

The discussion explores differing perspectives of their creators, as well as how foundational debates about technology and ethics continue to inform the present landscape of AI in mental health care.

🎧 Listen now.

JAMA+ AI Editor in Chief Roy Perlis, MD, MSc, conducted an interview with ChatGPT about the history of chatbots and their clinical applications, for JAMA+ AI Conversations.

Living ‘Mini Brains’ Meet Next-Generation Bioelectronics

A team led by Northwestern University and Shirley Ryan AbilityLab scientists have developed a new technology that can eavesdrop on the hidden electrical dialogues unfolding inside miniature, lab-grown human brain-like tissues, according to a study published the journal Nature Biomedical Engineering.

Known as human neural organoids — and sometimes called “mini brains” — these millimeter-sized structures are powerful models of brain development and disease. But until now, scientists could only record and stimulate activity from a small fraction of their neurons — missing network-wide dynamics that give rise to coordinated rhythms, information processing and the complex patterns of activity that define brain function.

For the first time, the new technology overcomes that stubborn limitation. The soft, three-dimensional (3D) electronic framework wraps around an organoid like a breathable, high-tech mesh. Rather than sampling select regions, it delivers near-complete, shape-conforming coverage with hundreds of miniaturized electrodes. That dense, three-dimensional interfacing enables scientists to map and manipulate neural activity across almost the entire organoid.

Astrocytes are critical for fear memory

The team used a mouse model to understand how fear learning as a mechanism takes place in the brain, how fear-related memories can be retrieved, and the contribution of neurons versus astrocytes to fear learning.

Using fluorescent activity sensors, the team watched astrocytes respond in real time as fear memories were formed and later retrieved. As those memories were extinguished, astrocyte activity diminished. When the researchers then selectively increased or suppressed the signals astrocytes send to neighboring neurons, the strength of fear memories shifted in parallel, demonstrating that astrocytes are not just passive bystanders, but active participants in shaping fear.

Change in astrocyte activity also influenced neural circuits. When the astrocyte activity was disrupted, neurons could no longer form normal fear-related activity patterns and effectively transmit information about appropriate defensive reactions to brain regions that help control defensive behavior. These findings challenge neuron-centric models of fear by showing that fear memories aren’t produced by neurons alone.

The impact of disrupting astrocytes rippled beyond the amygdala. The manipulations also influenced how fear signals were relayed to the prefrontal cortex, a brain region that is key for decision-making. This suggests that astrocytes not only influence encoding of fear memories by the amygdala, but also how the brain uses those memories to determine appropriate responses to fearful situations.

Knowing that astrocytes play a key role in the retrieval of fear memories will reshape therapeutic interventions for disorders driven by persistent fearful memories such as post-traumatic stress disorder, anxiety disorders and phobias, the author said. If astrocytes help determine whether fear memories are expressed or successfully extinguished, then targeting astrocyte-related pathways, rather than neural pathways, could eventually complement neuron-focused therapies.

Picture a star-shaped cell in the brain, stretching its spindly arms out to cradle the neurons around it. That’s an astrocyte, and for a long time, scientists thought its job was caretaking the brain, gluing together neurons, and maintaining neural circuits.

Continue reading “Astrocytes are critical for fear memory” | >

Liquid Crystal Monomers Released from LCD Displays Accumulate in Endangered Marine Cetaceans Triggering Health Concerns

Liquid crystal monomers (LCMs), critical substances of liquid crystal displays in consumer electronics, are persistent pollutants, posing potential threats to marine ecosystems. Despite their bioaccumulative potential, their occurrence and possible biological impacts on marine megafauna remain understudied. We investigated LCM occurrence in Indo-Pacific humpback dolphins (Sousa chinensis) and finless porpoises (Neophocaena phocaenoides) collected from the South China Sea (2007–2021) and assessed their toxicity through in vitro assays using established dolphin cell lines. By employing robust source-tracing methodologies, we provide the first evidence that LCMs from household electronics and coastal e-waste accumulate in cetacean tissues, including blubber, muscle, and, critically, brain tissues, demonstrating blood–brain barrier penetration, a previously undocumented phenomenon of LCMs in mammalian wildlife. The temporal trend of LCM burden in porpoise blubber is correlated with shifts in global liquid crystal display production. Transcriptomic profiling revealed LCM-induced DNA damage, cell cycle arrest, and impaired cell division in cetacean cells. These findings suggest that LCMs may pose potential risks to the nervous system and other organs of marine mammals, warranting further investigation into their toxicological effects and possible implications for human health. By bridging critical gaps among everyday electronics, LCM contamination, and marine conservation, this study highlights the need for urgent regulatory actions and improved e-waste governance to mitigate ecological and public health risks.

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