This cohort study examines whether diurnal salivary cortisol indices are associated with cognitive outcomes, including incident Alzheimer disease, and whether distributions and associations differ by race.
Category: neuroscience
Two hours of sleep restored: Researchers make Alzheimer’s breakthrough
There’s a small fire isolated in your kitchen. If you had the right tool, you might be able to put it out. But before you can, the sprinklers turn on and flood your entire house. An automatic response to an issue has now damaged everything you own.
That’s akin to what happens in the brains of people with Alzheimer’s: Amyloid plaques, sticky protein clumps that build up in the brain, are the fire in the kitchen. Microglia, the brain’s resident immune cells, are the sprinklers. A mechanism designed to protect the body ends up hurting it.
Researchers at the University of Kentucky have discovered this harmful process for the first time—and figured out how to turn it off.
Postnatal Development of Pyramidal Neurons Excitability and Synaptic Inputs in Mouse Gustatory Cortical Circuits
During postnatal development, mammals shift from relying on their mother’s milk to foraging for food. Early experience with feeding independence influences the development of taste preferences (Schiff et al., 2023). While the postnatal development of gustatory cortical circuits is not well studied, there is some experimental evidence for protracted maturation of neuronal morphology and early-life experience-dependent effects on neurons in other regions of the taste system. In mice, taste receptor cells begin to reliably fire action potentials during the third postnatal week (Bigiani et al., 2002) and the refinement of their excitability extends into adulthood (Bigiani et al., 2002; Ohtubo et al., 2012). Postnatal anatomical rewiring was observed in the first central relay in the gustatory system, the nucleus of the solitary tract (NTS) after postnatal day 21 (P21), with the inputs to the NTS reaching adult connectivity by P35 and undergoing additional refinement into adulthood (Hill et al., 1983; Sollars et al., 2006; May et al., 2008; Sun et al., 2017). In the gustatory portion of the parabrachial nucleus, dendritic arborization of multipolar and fusiform cells reach adult morphology by P35 (Lasiter and Kachele, 1988). Together, these studies identify the postnatal window between P15–P21, P21–P35, and P50–P65 as periods of maturation for different circuits in the gustatory system.
In primary visual, auditory, and somatosensory cortices, developmental time windows of heightened sensitivity to changes in sensory inputs extending between the third and fifth postnatal week have been identified (Micheva and Beaulieu, 1995; Antonini et al., 1999; Maffei et al., 2006, 2010; Maffei and Turrigiano, 2008b; Wang et al., 2011; Takesian et al., 2012, 2018; Gainey and Feldman, 2017; Gainey et al., 2018). During these periods, known as critical periods, cortical circuits undergo a maturation process that is shaped by experience and reach their adult properties.
GABAergic inhibitory synapses in particular play a crucial role in postnatal cortical circuit maturation and refinement. Inhibitory cortical circuits themselves undergo extended postnatal maturation (Hensch, 2004; Tatti et al., 2017; Takesian et al., 2018), with increases in GABAergic inhibition opening the critical period for circuit refinement. For instance, in a knock-out mouse in which GABA is severely diminished (GAD-KO), the critical period may never open unless GABA receptors are activated pharmacologically (Fagiolini and Hensch, 2000). Changes in inhibitory circuits during critical periods are primarily ascribed to parvalbumin-expressing interneurons (PV+ INs). Reports show an increase in the number of PV+ INs (Gonchar et al., 2007; Tatti et al., 2017) along with increased perisomatic innervation of pyramidal neurons (Chattopadhyaya et al., 2004). This process is associated with increases in the expression of PV in PV+ INs (Murase et al.
New mechanism explains how spinal stimulation improves arm movement after stroke
Researchers in the Neuromechatronics Lab at Carnegie Mellon University have already proven that spinal cord stimulation can help people regain movement after stroke, but until now they didn’t quite know how.
In a new study, published today in Cell Reports Medicine, a research team led by Doug Weber, professor of mechanical engineering and neuroscience, and Ph.D. candidate Luigi Borda report that epidural spinal cord stimulation works by restoring inhibitory spinal circuits. These circuits enable the nervous system to coordinate opposing muscles, such as the biceps and triceps, which must work together to bend and straighten the elbow. After a stroke, those neural control circuits are disrupted. The new study found that spinal cord stimulation helps restore that balance, allowing stroke survivors to move their arms more smoothly, quickly and efficiently.
“This discovery allows us to move beyond simply strengthening weak muscles; we can now fine-tune stimulation to release the ‘brakes’ on overactive muscles, providing a more effective and personalized path to recovery,” said Weber.
Sugarcoated nanoparticles show promise for treating most aggressive form of brain cancer
Sugar-coated nanoparticles show promise against glioblastoma.
Researchers have developed mannose-coated lipid nanoparticles capable of crossing the blood-brain barrier and delivering therapeutic PTEN mRNA directly to glioblastoma cells, one of the deadliest forms of brain cancer.
Glioblastoma cells have an exceptionally high demand for glucose. By coating the nanoparticles with a sugar molecule called mannose, the researchers took advantage of this metabolic feature, allowing the particles to enter the brain more efficiently and accumulate within tumors.
Once inside the cancer cells, the nanoparticles restored production of PTEN, a critical tumor-suppressor protein that is frequently lost or dysfunctional in glioblastoma. In mouse models, this approach significantly slowed tumor growth, increased median survival by approximately 50%, and showed no measurable toxicity in major organs.
Although these findings are still preclinical and have not yet been tested in humans, they represent an exciting advance in overcoming one of neuro-oncology’s greatest challenges: safely delivering targeted therapies across the blood-brain barrier.
PORTLAND, Ore. – Researchers at Oregon State University have potentially found a new way to treat the most aggressive form of brain cancer, glioblastoma, whose two-year survival rate is less than 30%.
Finding the RNA aptamer in the haystack that could improve treatment for Parkinson’s
Synucleinopathies are a group of neurodegenerative disorders that include serious conditions such as Parkinson’s disease and dementia with Lewy bodies. There are currently no cures for these disorders, and treatment is limited to mitigating symptoms. Recently, antibody-based therapies have attracted considerable attention, but alternative approaches are still necessary.
Therapy development for synucleinopathies tends to target the alpha-synuclein protein, αSyn, the abnormal aggregation of which is a hallmark of these diseases. However, targeting this protein using conventional drug discovery strategies is stymied by the molecule’s lack of a stable three-dimensional structure, which promotes aggregation.
Interested in understanding how abnormal protein aggregation drives neurodegeneration, a team of researchers at Kyoto University had an idea that was both scientifically intriguing and therapeutically promising: Could RNA aptamers—often described as “chemical antibodies”—directly recognize αSyn’s disordered regions and suppress pathological aggregation?
Gene therapy restores key fragile X traits in preclinical study
A gene therapy designed to replace the missing protein that causes fragile X syndrome restored several disease-relevant traits in a mouse model, according to a new study published in Gene Therapy.
Fragile X syndrome is the most common inherited form of intellectual disability and a leading single-gene condition associated with autism. There is no cure, and current care focuses on managing symptoms such as anxiety, sensory sensitivity, hyperactivity, developmental seizures and learning challenges.
The study, led by investigators at Cincinnati Children’s and collaborators at Forge Biologics, tested adeno-associated viral vectors carrying human FMR1, the gene silenced in fragile X syndrome. After testing several candidates, the team found an approach that produced the FMRP protein in key brain regions and improved multiple phenotypes in Fmr1 knockout mice.
Dendrites may be key to learning and memory, study suggests
Branchlike structures called dendrites that extend from neurons appear to make their own computations independent of the cell body, helping individual brain cells store memories of the past, respond to the present and anticipate the future, a study led by UT Southwestern Medical Center researchers suggests.
The findings, published in Science, represent a paradigm shift in current models of how learning and memory take place.
“This shifts our entire perspective. Rather than acting as simple switches, neurons behave more like sophisticated processors with internal divisions of labor, dramatically increasing the brain’s computational capacity,” said Attila Losonczy, M.D., Ph.D., professor at the Peter O’Donnell Jr. Brain Institute of Neuroscience and director of the Program in Memory Longevity (PML) at UT Southwestern.
Human-machine learning boosts noninvasive brain-computer control in untrained users
Implantable devices in the brain have been used for about 30 years to assist people with disabilities in completing motor tasks. However, the devices are simply not accessible to the vast majority of people who need help. Despite decades of work in this field, fewer than 100 people worldwide have benefited from the technology. The costs are prohibitive, and the brain surgeries are inherently risky.
That’s why Carnegie Mellon researchers, including Bin He, professor of biomedical engineering, electrical and computer engineering, and the Neuroscience Institute, have long been working on noninvasive brain-computer interfaces (BCIs) to develop technology that is less expensive, safer and more accessible to a wider population. Over the past 10 to 15 years, they have used noninvasive BCIs to fly a drone, control a robotic arm, maintain continuous control of a robotic arm and, most recently, complete fine motor tasks at the finger level. Yet the accuracy and level of control using noninvasive technology remain challenging.