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Category: neuroscience – Page 37
Tau mutation drives autophagy-lysosome dysfunction
The researchers studied a specific mutation in a brain protein called tau that causes the protein to become misfolded and alter its normal function. In general, when tau proteins become misfolded, they build up inside neurons and contribute to various forms of dementia, including Alzheimer’s dementia and frontotemporal dementia, a neurodegenerative disease similar to Alzheimer’s that often strikes earlier — in middle age — and typically involves significant changes in personality and behavior that precede cognitive decline.
In this new study, the researchers studied neurons that had been reprogrammed from skin cells sampled from patients with frontotemporal dementia who carried the tau mutation. In the neurons, the mutated tau proteins caused waste-recycling centers called lysosomes, which are involved in autophagy, to become dysfunctional, allowing cellular waste to accumulate in the lysosomes, which may contribute to neuronal death. The researchers found that enhancing autophagy with an analog of the chemical compound G2 improved clearance of the garbage, reduced tau levels in the lysosomes and prevented cellular toxicity and death.
G2 was discovered in 2019 via screening experiments seeking drugs that could reduce the accumulation of an aggregation-prone protein in a C. elegans model of alpha-1-antitrypsin deficiency, which can cause severe liver disease. The compound was later shown to boost autophagy function in mammalian cell model systems.
The researchers also have shown that G2 can protect brain cells from death in cells modeling Huntington’s disease, a fatal inherited neurodegenerative disease caused by a genetic mutation present at birth. In the cellular model of Huntington’s disease, the compound prevented the buildup of a harmful RNA molecule. ScienceMission sciencenewshighlights.
New research adds to growing evidence that helping brain cells break down and eliminate their own cellular waste is a promising treatment strategy for a variety of neurodegenerative diseases. In lab experiments, the researchers found that exposure to a novel compound can clear a harmful protein from human neurons modeling frontotemporal dementia — a devastating and ultimately fatal condition — and prevent those neurons from dying.
The study is published in the journal Nature Communications.
Body-focused mind-wandering associated with better mental health outcomes, finds new study
Most of us have experienced that when our body is still and resting, the mind doesn’t stop. Instead, it takes off on its own journey of generating thoughts about our past, our plans, and the people around us, a process known as mind-wandering. While researchers have learned a lot about these kinds of thoughts, there aren’t many studies that explore how often our attention turns inward, toward sensations in our bodies, such as our breathing, heartbeat, or physical feelings.
This lesser-known side of our inner experience, called body-wandering, is what a recent study by a brain research team with collaborators from Denmark, Canada and Germany set out to explore.
To understand how the mind focuses on the physical self, researchers conducted a large-scale study with 536 participants who were asked to stay still in the MRI machine during a brain scan while looking at a cross on the screen above them.
People use the same neurons to see and imagine objects, study shows
Why can images of things we have seen seem so real when we later recall them from memory? A new study led by Cedars-Sinai Health Sciences University investigators sheds light on the answer. The research shows that the same brain neurons are activated when we imagine something and when we perceive something. The research, led by Cedars-Sinai, is the first to provide a detailed understanding of the shared mechanism that underlies visual perception and creation of mental images in the human brain. It was published in the journal Science.
“We generate a mental image of an object that we have seen before by reactivating the brain cells we used to see it in the first place,” said Ueli Rutishauser, Ph.D., director of the Center for Neural Science and Medicine and professor of Neurosurgery, Neurology and Biomedical Sciences at Cedars-Sinai Health Sciences University, and the study’s joint senior author.
“Our study revealed the code that we use to re-create the images.”
How the blood-brain barrier opens: Two proteins may guide future drug delivery
The cells that line the blood vessels in our brains are highly selective. By deciding which molecules are allowed in and out of our most important organ, the barrier these cells form is critical for keeping us alive. But how the brain chooses what passes beyond this barrier has been difficult to decipher.
Now, a team led by Janelia Research Campus Group Leader Jiefu Li has developed a new method to examine the proteins lining the inside surface of blood vessels. The technique enables them to uncover two proteins and pathways that play a role in opening and closing the blood-brain barrier—a first step in starting to understand how this important interface works. The study is published in the journal Science.
Uncovering how the blood-brain barrier functions could help scientists figure out what happens when it goes awry, contributing to conditions like multiple sclerosis, encephalitis, and dementia. It could also help researchers develop better ways to deliver medicines that treat neurodegenerative diseases like Alzheimer’s and Parkinson’s, which are often blocked from entering the brain.
Lab-grown pineal gland organoids produce melatonin, offering a new sleep model
Organoids are miniature, simplified versions of an organ. Over the past two decades, scientists have developed them for the gut, lung, liver, mammary gland, brain, and more. Now, researchers at Yale School of Medicine (YSM) have organoid-ized the pineal gland, a small structure in the brain that regulates sleep patterns through its production of the hormone melatonin.
In a study published in Cell Stem Cell, the researchers demonstrate how pineal gland organoids can be used to study sleep dysfunction in conditions like Angelman syndrome, autism, and depression.
“In a number of neuropsychiatric conditions, severe sleep problems are a major symptom,” says In-Hyun Park, Ph.D., associate professor of genetics at YSM and senior author of the study. “With pineal gland organoids, we may be able to uncover the causes of those sleep disturbances and possibly identify treatments.”
Sound-sensing hair bundles in our ears act as tiny thermodynamic machines
The hair cells lining the inner ear are among the most sophisticated structures in the human body: capable of detecting sounds as faint as a whisper, while helping to maintain our sense of balance. Through new models detailed in PRX Life, a team led by Roman Belousov at the European Molecular Biology Laboratory has revealed for the first time how oscillating bundles attached to these cells operate in different thermodynamic regimes—offering a new framework for understanding how our hearing works at a fundamental level.
Within the inner ear, each hair cell hosts a hair “bundle”: a cluster of tiny, bristle-like projections that vibrate in response to incoming sound waves. The mechanical energy from these oscillations is then converted into electrical signals which travel to the brain. Rather than being passive receivers, these bundles actively oscillate —driven by molecular motors within the cell that allow them to amplify faint signals and tune in to specific frequencies.
But despite decades of study, researchers are still unclear on the connection between this active oscillation and the hair bundle’s response to external sound. Existing models tended to treat bundles as if they were moving spontaneously, without accounting for what happens when they actually interact with sound.