And they have reason to believe their treatment could translate to humans.
Category: neuroscience – Page 768
Fresh insights into damaging proteins that build up in the brains of people with Alzheimer’s disease could aid the quest for treatments.
A study in mice reveals how the two proteins work together to disrupt communication between brain cells.
Scientists observed how proteins—called amyloid beta and tau—team up to hamper key genes responsible for brain messaging. By changing how genes are expressed in the brain, the proteins can affect its normal function.
The procedure, donation after circulatory death or DCD, involves taking organs from a donor whose heart has stopped beating after being taken off of life support after a fatal injury or illness when there is no potential for recovery.
Conventional organ donations occur after brain death, which means that while all brain functions have stopped and the person is legally and clinically dead, machines can continue to keep oxygen and blood flowing throughout the body, preserving the healthy organs for donation.
After a circulatory death, however, organs are deprived of oxygen as the circulatory system shuts down, potentially damaging the donor organs and making it difficult to use them for transplant.
In mouse models of Alzheimer’s disease, the investigational drug candidates known as CMS121 and J147 improve memory and slow the degeneration of brain cells. Now, Salk researchers have shown how these compounds can also slow aging in healthy older mice, blocking the damage to brain cells that normally occurs during aging and restoring the levels of specific molecules to those seen in younger brains.
The research, published last month in the journal eLife, suggests that the drug candidates may be useful for treating a broader array of conditions and points out a new pathway that links normal aging to Alzheimer’s disease.
“This study further validated these two compounds not only as Alzheimer’s drug candidates but also as potentially more widely useful for their anti-aging effects,” says Pamela Maher, a senior staff scientist at Salk and a co-corresponding author of the new paper.
Summary: Researchers reveal the right homologue of the Broca’s area plays a major role in the processing of music.
Source: Max Planck Institute.
Vincent Cheung, along with Angela Friederici, has been investigating non-local dependencies in music and trying to determine how the human brain processes them. In language and music, dependencies are conceptual threads that bind two things together. Non-local dependencies bind non-adjacent items. For example, in pop music, the second instance of a verse, following a chorus, would have a non-local dependency with the first instance of the verse. Experientially, it is clear to us that we are hearing a sequence that we have heard before. According to Cheung, composers use such devices to build up our expectations and elicit strong emotional responses to the music. But how does the brain recognize these patterns and what does this have to do with Paul Broca?
Using a targeted gene epigenome editing approach in the developing mouse brain, Johns Hopkins Medicine researchers reversed one gene mutation that leads to the genetic disorder WAGR syndrome, which causes intellectual disability and obesity in people. This specific editing was unique in that it changed the epigenome—how the genes are regulated—without changing the actual genetic code of the gene being regulated.
The researchers found that this gene, C11orf46, is an important regulator during brain development. Specifically, it turns on and off the direction-sensing proteins that help guide the long fibers growing out of newly formed neurons responsible for sending electrical messages, helping them form into a bundle, which connects the two hemispheres of the brain. Failure to properly form this bundled structure, known as the corpus callosum, can lead to conditions such as intellectual disability, autism or other brain developmental disorders.
“Although this work is early, these findings suggest that we may be able to develop future epigenome editing therapies that could help reshape the neural connections in the brain, and perhaps prevent developmental disorders of the brain from occurring,” says Atsushi Kamiya, M.D., Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.
A ketone-supplemented diet may protect neurons from death during the progression of Alzheimer’s disease, according to research in mice recently published in JNeurosci.
Early in the development of Alzheimer’s disease, the brain becomes over excited, potentially through the loss of inhibitory, or GABAergic, interneurons that keep other neurons from signaling too much. Because interneurons require more energy compared to other neurons, they may be more susceptible to dying when they encounter the Alzheimer’s disease protein amyloid beta. Amyloid beta has been shown to damage mitochondria — the metabolic engine for cells — by interfering with SIRT3, a protein that preserves mitochondrial functions and protects neurons.
Cheng et al. genetically reduced levels of SIRT3 in mouse models of Alzheimer’s disease. Mice with low levels of SIRT3 experienced a much higher mortality rate, more violent seizures, and increased interneuron death compared to the mice from the standard Alzheimer’s disease model and control mice. However, the mice with reduced levels of SIRT3 experienced fewer seizures and were less likely to die when they ate a diet rich in ketones, a specific type of fatty acid. The diet also increased levels of SIRT3 in the mice.
The blood-brain barrier, a region of dense cells and blood vessels, keeps drugs from reaching deep parts of the brain. West Virginia University scientists temporarily opened it with ultrasound.
Doctors at Duke University Medical Center this month “reanimated” a heart for a first-of-its-kind transplant performed on an adult in the United States.
Heart transplants typically come from donations after brain death, in which the still-beating heart of a person who has been declared brain dead is transplanted into a recipient. The approach used at Duke is known as a donation after circulatory death (DCD), and it relies on hearts that have stopped beating and are essentially reanimated and begin beating again.
The TransMedics Organ Care System, a warm perfusion pump, allows doctors to resuscitate and preserve hearts for transplantation. The system was used for the adult donation after circulatory death transplant at Duke University Medical Center, one of five centers in the United States approved by the US Food and Drug Administration for clinical trials of the TransMedics system.
Drugs that tamp down inflammation in the brain could slow or even reverse the cognitive decline that comes with age.
University of California, Berkeley, and Ben-Gurion University scientists report that senile mice given one such drug had fewer signs of brain inflammation and were better able to learn new tasks, becoming almost as adept as mice half their age.
“We tend to think about the aged brain in the same way we think about neurodegeneration: Age involves loss of function and dead cells. But our new data tell a different story about why the aged brain is not functioning well: It is because of this “fog” of inflammatory load,” said Daniela Kaufer, a UC Berkeley professor of integrative biology and a senior author, along with Alon Friedman of Ben-Gurion University of the Negev in Israel and Dalhousie University in Canada. “But when you remove that inflammatory fog, within days the aged brain acts like a young brain. It is a really, really optimistic finding, in terms of the capacity for plasticity that exists in the brain. We can reverse brain aging.”