Understanding synapse loss in Alzheimer’s disease has been hampered by a lack of human model systems. Here, the authors show that manipulation of physiological or pathological Aβ has differing effects on synapses in live human brain slice cultures.

Author summary Humans exhibit a remarkable ability to regulate their actions in response to changing environmental demands. An essential aspect of action regulation is action inhibition that occurs when stopping unwanted or inappropriate actions. However, everyday life rarely calls for complete inhibition of responses without switching behavior to adapt to new situations. Despite extensive research to understand how the brain switches actions, the computations underlying the switching process and how it relates to the selecting and stopping processes remain elusive. Part of this challenge lies in the fact that these processes are rarely studied together, making it difficult to develop a unified theory that explains the computational aspects of the action regulation mechanism. The current study aims to delineate the computations underlying action regulation functions that involve inhibitory control, explore how these functions interrelate, and how they can be implemented within brain networks, opening new avenues for future neurophysiological investigations.

The protective role of ATP in neurons reduces protein aggregation and neurodegeneration.

UCLA researchers have made a significant breakthrough in stroke rehabilitation by developing a drug, DDL-920, that replicates the effects of physical therapy in mice. This discovery could pave the way for new treatments that enhance recovery for stroke patients.

Key Findings:

- Understanding Stroke-Induced Brain Disconnection: The study revealed that strokes can disrupt brain connections far from the initial damage site, particularly affecting parvalbumin neurons. These neurons are crucial for generating gamma oscillations—brain rhythms essential for coordinated movements.

- Role of Physical Rehabilitation: Physical therapy was found to restore gamma oscillations and repair connections in parvalbumin neurons, leading to improved motor functions in both mice and human subjects.

The identification of peripheral neural stem cells could transform the treatment of Parkinson’s disease and spinal cord injuries

Complex neural circuits likely arose independently in birds and mammals, suggesting that vertebrates evolved intelligence multiple times.

More Americans are receiving computed tomography (CT) scans than ever before, and while this technology can save lives, some scientists are concerned about the potential for low doses of ionizing radiation to increase cancer risks.

A study from Tübingen University and the German Center for Diabetes Research reveals that the brain plays a crucial role in obesity and type 2 diabetes development. It shows that even a brief period of consuming high-calorie processed foods can significantly alter brain insulin sensitivity, a key factor in weight gain and metabolic disorders. The research demonstrated that insulin’s appetite-suppressing effect in the brain diminishes after a short-term high-calorie diet, leading to insulin resistance. These effects were observed in healthy participants, suggesting that dietary habits could influence brain function before any significant weight gain occurs. Further research is needed to understand the brain’s role in these conditions.

The number of obese persons has grown significantly in recent decades, which presents significant difficulties for those who are impacted, healthcare systems, and those who provide treatment. The hormone insulin plays a key role in the development of obesity. Up until recently, there have been numerous signs indicating insulin causes neurodegenerative and metabolic disorders, especially in the brain. A recent study by the University Hospital of Tübingen, the German Center for Diabetes Research (DZD), and Helmholtz Munich offers intriguing new insights into the origins of type 2 diabetes and obesity as well as the brain’s function as a critical control center.

Obesity has only been officially recognized as a disease in Germany since 2020, despite the fact that it has long been known to cause a number of illnesses, including diabetes, heart attacks, and even cancer. The World Health Organization has already declared obesity to be an epidemic, affecting over one billion individuals globally and almost 16 million in Germany alone. A body mass index of 30 or more is considered obese, and a poor diet and insufficient exercise are frequently cited as the causes of this chronic illness. However, the mechanisms in the body that lead to obesity and cause the disease are more complex.

Obesity and the role of insulin in the brain

Unhealthy body fat distribution and chronic weight gain are linked to the brain’s sensitivity to insulin. What specific functions does insulin perform in the brain, and how does it affect individuals of normal weight? In their study, Prof. Dr. Stephanie Kullmann and her colleagues at the Tübingen University Hospital for Diabetology, Endocrinology, and Nephrology found the answer to this query. “Our findings demonstrate for the first time that even a brief consumption of highly processed, unhealthy foods (such as chocolate bars and potato chips) causes a significant alteration in the brain of healthy individuals, which may be the initial cause of obesity and type 2 diabetes,” says Prof. Kullmann, the study’s leader. In a healthy state, insulin has an appetite-suppressing effect in the brain. However, in people with obesity in particular, insulin no longer regulates eating behavior properly, resulting in insulin resistance.

The study, “Endothelial TDP-43 Depletion Disrupts Core Blood-Brain Barrier Pathways in Neurodegeneration,” was published on March 14, 2025. The lead author, Omar Moustafa Fathy, an MD/Ph. D. candidate at the Center for Vascular Biology at UConn School of Medicine, conducted the research in the laboratory of senior author Dr. Patrick A. Murphy, associate professor and newly appointed interim director of the Center for Vascular Biology. The study was carried out in collaboration with Dr. Riqiang Yan, a leading expert in Alzheimer’s disease and neurodegeneration research.

This work provides a novel and significant exploration of how vascular dysfunction contributes to neurodegenerative diseases, exemplifying the powerful collaboration between the Center for Vascular Biology and the Department of Neuroscience. While clinical evidence has long suggested that blood-brain barrier (BBB) dysfunction plays a role in neurodegeneration, the specific contribution of endothelial cells remained unclear. The BBB serves as a critical protective barrier, shielding the brain from circulating factors that could cause inflammation and dysfunction. Though multiple cell types contribute to its function, endothelial cells—the inner lining of blood vessels—are its principal component.

“It is often said in the field that ‘we are only as old as our arteries’. Across diseases we are learning the importance of the endothelium. I had no doubt the same would be true in neurodegeneration, but seeing what these cells were doing was a critical first step,” says Murphy.

Omar, Murphy, and their team tackled a key challenge: endothelial cells are rare and difficult to isolate from tissues, making it even harder to analyze the molecular pathways involved in neurodegeneration.

To overcome this, they developed an innovative approach to enrich these cells from frozen tissues stored in a large NIH-sponsored biobank. They then applied inCITE-seq, a cutting-edge method that enables direct measurement of protein-level signaling responses in single cells—marking its first-ever use in human tissues.

This breakthrough led to a striking discovery: endothelial cells from three different neurodegenerative diseases—Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD)—shared fundamental similarities that set them apart from the endothelium in healthy aging. A key finding was the depletion of TDP-43, an RNA-binding protein genetically linked to ALS-FTD and commonly disrupted in AD. Until now, research has focused primarily on neurons, but this study highlights a previously unrecognized dysfunction in endothelial cells.

“It’s easy to think of blood vessels as passive pipelines, but our findings challenge that view,” says Omar. “Across multiple neurodegenerative diseases, we see strikingly similar vascular changes, suggesting that the vasculature isn’t just collateral damage—it’s actively shaping disease progression. Recognizing these commonalities opens the door to new therapeutic possibilities that target the vasculature itself.”

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“The findings are significant because they could pave the way for new treatments to keep the brain healthier longer,” says Agustín Ibáñez, a neuroscientist at Trinity College Dublin. “But much more research is needed before these findings can be applied in practice.”