Israeli scientists gave an artificial molecule they invented to 30 mice suffering from Alzheimer’s — and found that all of them recovered, regaining full cognitive abilities. They stress that this was a small sample of mice and that human testing is far off, but believe the result indicates that within a decade, their synthetic molecule could be developed into a drug for treating the degenerative disease. The peer-reviewed research, led by neuroscientists from Ben-Gurion University, was recently published in the journal Translational Neurodegeneration.

“We are taking a very different approach than efforts at Alzheimer’s medicines that we have seen so far,” Prof. Varda Shoshan-Barmatz, the lead author, told The Times of Israel. “Most are trying to address plaque that forms in the brain, but we are addressing dysfunction elsewhere. And we’re optimistic. Mice who had Alzheimer’s and received our molecule and then underwent tests had the same cognitive abilities as mice who’d never had Alzheimer’s.”

Interestingly, the molecule appears to have been effective without significantly reducing the amount of plaque, which she thinks indicates that scientists may have been overly fixated on the plaque. There is scientific literature on the dysfunction of mitochondria among people with Alzheimer’s. Mitochondria are organelles — tiny miniature organs within cells — that provide the cell with power. Scientists believe that when they malfunction and fail to produce the normal quantities of energy, it can lead to cell death, inflammation and reduced immune response.

Despite Alzheimer’s being linked to mitochondrial dysfunction, no drug candidates are currently focused on mitochondria. Drug research is mostly concerned with combatting the buildup of protein fragments between nerve cells in the brain, which are thought to be linked to Alzheimer’s. The Ben-Gurion University team set out to normalize mitochondrial activity by countering the harmful effects that occur when a protein called VDAC1 is over-produced. The protein plays a crucial role in regulating the metabolic and energetic functions of mitochondria when produced in normal quantities. But the scientists found that it is produced in huge levels in the brains of mice with Alzheimer’s, and interferes with mitochondrial activity.

“In our research, we have shifted the focus of Alzheimer’s treatments from the plaque to this protein, which is produced in the nerve cells around the plaque instead,” said Shoshan-Barmatz. “We prevent this protein from causing cell death, as the molecule interferes with its harmful effect.”

Source: https://in.bgu.ac.il/ 
AND
https://www.timesofisrael.com/

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New research in the journal Nature Aging takes a page from the field of renewable energy and shows that genetically engineered mitochondria can convert light energy into chemical energy that cells can use, ultimately extending the life of the roundworm C. elegans.  While the prospect of sunlight-charged cells in humans is more science fiction than science, the findings shed light on important mechanisms in the aging process.

Caenorhabditis elegans (C. elegans) has been the source of major discoveries in molecular and cell biology

“We know that mitochondrial dysfunction is a consequence of aging,” said Andrew Wojtovich, Ph.D., associate professor of Pharmacology & Physiology at the University of Rochester Medical Center and senior author of the study.  “This study found that simply boosting metabolism using light-powered mitochondria gave laboratory worms longer, healthier lives.  These findings and new research tools will enable us to further study mitochondria and identify new ways to treat age-related diseases and age healthier.”

Mitochondria are organelles found in most cells in the body.  Often referred to as cellular power plants, mitochondria use glucose to produce adenosine triphosphate (ATP), the compound that provides energy for key functions in the cell, such as muscle contraction and the electrical impulses that help nerve cells communicate with each other.

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In a bit of “reverse engineering” research using brain tissues from five people who died with Alzheimer’s disease, Johns Hopkins Medicine researchers say they discovered that a special sugar molecule could play a key role in the development of Alzheimer’s disease. If further research confirms the finding, the molecule, known as a glycan, could serve as a new target for early diagnostic tests, treatments and perhaps prevention of Alzheimer’s disease, say the researchers. Alzheimer’s disease is the most common form of dementia in the United States. Affecting an estimated 5.8 million Americans, the progressive disorder occurs when nerve cells in the brain die due to the buildup of harmful forms of proteins called amyloid and tau.

Cleaning up the disease-causing forms of amyloid and tau is the job of the brain’s immune cells, called microglia. Earlier studies found that when cleanup is impaired, Alzheimer’s disease is more likely to occur. In some people, this is caused by an overabundance of a receptor on the microglia cells, called CD33.

“Receptors are not active on their own. Something needs to connect with them to block microglia from cleaning up these toxic proteins in the brain", says Ronald Schnaar,  Professor of Pharmacology at the Johns Hopkins University School of Medicine and director of the laboratory that led the study. Past studies by the researchers showed that for CD33, these “connector” molecules are special sugars. Known to scientists as glycans, these molecules are ferried around the cell by specialized proteins that help them find their appropriate receptors. The protein-glycan combination is called a glycoprotein.

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A team of researchers affiliated with multiple institutions in Germany has developed a cochlear implant that converts sound waves to light signals instead of electrical signals. In their paper published in the journal Science Translational Medicine, the group describes their new hearing aid and how well it worked in test rats.

Cochlear implants work by converting sound waves into electrical signals that are sent to nerve cells in the ear. The idea is to bypass damaged hair cells inside the cochlea to restore hearing. But because the fluid in the ear also conducts electricity, the electrical signals that are generated can cross, leading to a loss of resolution. The result is difficulty hearing in some situations, such as crowded rooms, or when listening to music with a lot of instruments. In this new effort, the researchers sought to replace the electrical signals in such devices with light signals, which would not be muddied by the fluid in the ear, and thereby improve hearing.

In all types of cochlear devices, sound entering the ear is directed to a computer chip that processes the sound it detects. After processing, the chip directs another device to create signals that are sent to the neurons. With the new device, the researchers developed a device that would generate light using LED chips and send it through fiber cable directly to the nerve cells.

In order for such a system to work, the nerve cells inside the ear would have to be modified in some way to allow them to respond to light instead of electricity. For testing purposes, the researchers genetically modified lab rats to grow nerve cells in their ears that would respond to light. In their device, they used an implant with 10 LED chips. They also trained the rats to respond to different sounds before disabling their hair cells and implanting the cochlear devices. The implants worked as hoped, as the rats were able to respond in similar ways to the same generated sounds.

The researchers suggest that in people, such a device would use 64 LED or other light source channels. They also plan to conduct more research with the device and hope to start clinical trials by 2025.

Source: https://medicalxpress.com/

Doctors regard amyloid plaque lodged between the brain’s nerve cells and tangled tau protein fibers forming within the cells as the hallmark of Alzheimer’s disease. However, amyloid plaque — consisting of broken pieces of protein that clump together — is also present in the brains of older adults who do not develop Alzheimer’s, suggesting another factor is triggering the disease.

A new study finds that inflammation in the brain drives the progression from the presence of amyloid plaque and tau tangles to the onset of dementia and Alzheimer’s disease.
Lead author of the study, Dr. Tharick Pascoal, Ph.D., assistant professor of psychiatry and neurology at the University of Pittsburgh School of Medicine, PA, explains:

“Many [older adults] have amyloid plaques in their brains but never progress to developing Alzheimer’s disease. We know that amyloid accumulation on its own is not enough to cause dementia — our results suggest that it is the interaction between neuroinflammation and amyloid pathology that unleashes tau propagation and eventually leads to widespread brain damage and cognitive impairment.”

While scientists have observed neuroinflammation in people with Alzheimer’s before, the new study reveals for the first time its critical role in the development of the disease. The research finds that activating the brain’s immune cells — its microglial cells — promotes the spread of tangled tau proteins that comprise amyloid plaque.

Heather M. Snyder, Ph.D., Alzheimer’s Association vice president of medical and scientific relations, who was not involved in the study, explained the purpose of neuroinflammation to Medical News Today. The Alzheimer’s Association contributed funding to the research.

“Inflammation has an important role in fighting off infection and other pathogens in the body, including in the brain and central nervous system,” said Snyder. Microglia “help clear debris (damaged neurons, infections) from the brain.” “However,” adds Dr. Snyder, “a sustained inflammatory response, or a change from acute to chronic neuroinflammation, may contribute to the underlying biology of several neurodegenerative disorders.”

Inflammation is not by itself associated with cognitive impairment, daid Dr. Pascoal. “However when neuroinflammation converges with amyloid pathology, the interaction potentiates tau pathology. As a consequence, the coexistence of these three processes in the brain — amyloid, neuroinflammation, and tau pathology — determines cognitive deterioration.”

“Results suggest that the combination of anti-amyloid with anti-inflammatory therapies in the early stages of the disease, when the pathology of tau is still confined to the temporal cortex, would maximize the efficacy of these drugs.”

The study appears in Nature Medicine.

Source: https://www.medicalnewstoday.com/

The cerebral cortex is the thin surface layer of the brain found in vertebrate animals that has evolved most recently, showing the greatest variation in size among different mammals (it is especially large in humans). Each part of the cerebral cortex is six layered (e.g., L2), with different kinds of nerve cells (e.g., spiny stellate) in each layer. The cerebral cortex plays a crucial role in most higher level cognitive functions, such as thinking, memory, planning, perception, language, and attention. Although there has been some progress in understanding the macroscopic organization of this very complicated tissue, its organization at the level of individual nerve cells and their interconnecting synapses is largely unknown.

Petabyte connectomic reconstruction of a volume of human neocortex. Left: Small subvolume of the dataset. Right: A subgraph of 5000 neurons and excitatory (green) and inhibitory (red) connections in the dataset. The full graph (connectome) would be far too dense to visualize.

Mapping the structure of the brain at the resolution of individual synapses requires high-resolution microscopy techniques that can image biochemically stabilized (fixed) tissue. We collaborated with brain surgeons at Massachusetts General Hospital in Boston (MGH) who sometimes remove pieces of normal human cerebral cortex when performing a surgery to cure epilepsy in order to gain access to a site in the deeper brain where an epileptic seizure is being initiated. Patients anonymously donated this tissue, which is normally discarded, to our colleagues in the Lichtman lab. The Harvard researchers cut the tissue into ~5300 individual 30 nanometer sections using an automated tape collecting ultra-microtome, mounted those sections onto silicon wafers, and then imaged the brain tissue at 4 nm resolution in a customized 61-beam parallelized scanning electron microscope for rapid image acquisition.

Imaging the ~5300 physical sections produced 225 million individual 2D images. The team then computationally stitched and aligned this data to produce a single 3D volume. While the quality of the data was generally excellent, these alignment pipelines had to robustly handle a number of challenges, including imaging artifacts, missing sections, variation in microscope parameters, and physical stretching and compression of the tissue. Once aligned, a multiscale flood-filling network pipeline was applied (using thousands of Google Cloud TPUs) to produce a 3D segmentation of each individual cell in the tissue. Additional machine learning pipelines were applied to identify and characterize 130 million synapses, classify each 3D fragment into various “subcompartments” (e.g., axon, dendrite, or cell body), and identify other structures of interest such as myelin and cilia. Automated reconstruction results were imperfect, so manual efforts were used to “proofread” roughly one hundred cells in the data. Over time, the scientists expect to add additional cells to this verified set through additional manual efforts and further advances in automation.

Source: https://ai.googleblog.com/

Your brain has its own box of memories. If you were to hold it in your hand, brush off the dust and open it up, you’d be able to pull out Polaroid snaps of your most treasured memories. Your graduation ceremony perhaps, your wedding day, your daughter’s first words – all things you wouldn’t want to forget. But how does your brain keep these memories in their crystal-clear clarity? The strength of a memory lies in its formation and upkeep. When we create a memory, thin connections, called axons, form between nerve cells in our brain. The point at which two axons connect is called a synapse, and it is the strength of the synapse that determines if the memory is kept or allowed to fade away.

Now, a study in mice carried out by Nobel Prize-winning researchers at Columbia University has shown that a protein called CPEB3 plays an important role in the formation of memories. The team discovered how this protein is stored and used in the brain and hope it could lead to new methods of slowing memory loss in humans.

“The science of how synapses form and are strengthened over time is important for deciphering any disorder in which synapses – and the memories associated with them – degrade and die, such as Alzheimer’s disease,” said Dr Luana Fioriti. CPEB3 is created by the brain’s memory centre, the Hyppocampus. Once produced, it is stored in chamber-like structures called P bodies that protect it from other parts of the cell. It then travels to the synapse between nerve cells where required and is gradually released to help create a specific memory.

The findings suggest that the more CPEB3 released at a synapse, the stronger the connection and thus, the more concrete the resulting memory is. When the protein was removed, the mice could create new memories but were unable to keep them.

Source: https://www.sciencefocus.com/

What is graphene foam? It’s a synthetic “wonder material” made from the same carbon atoms that make up the lead in a pencil. Graphene foam can be used as a “bioscaffold” to mesh with human stem cells and grow new cartilage. In addition to being incredibly strong, graphene foam conducts heat and electricity which helps neurons, or nerve cells, transmit information. Boise State researchers believe graphene foam-enhanced cartilage could one day be used to treat the joint pain caused by osteoarthritis as well as prevent the need for joint replacement. Osteoarthritis is incurable and affects half the U.S. population over the age of 65.

“If we could take graphene foam, adhere a patient’s own stem cells on it then and inject that into someone’s knee to regrow their own cartilage, that would be the ‘pie in the sky,‘” said Dave Estrada, co-director of the Boise State University’s Advanced Nanomaterials and Manufacturing Laboratory.

A Boise State team led by Katie Yocham, a doctoral student in the Micron School of Materials Science and Engineering, and Estrada have published a study, “Mechanical Properties of Graphene Foam and Graphene Foam-Tissue Composites,” in the Advanced Engineering Materials journal.

While earlier studies at Boise State have shown that graphene foam is compatible with cells for growing new cartilage tissue, this is the first study to investigate how that tissue would actually function in a human joint under normal stresses, including high impact activities.

Trevor Lujan, an associate professor in the Department of Mechanical and Biomedical Engineering, and one of the authors of the study, praised Yocham’s work. “Katie’s strong efforts on this project have provided the biomedical community with a rigorous characterization of the bulk mechanical behavior of cellularized graphene foam. This baseline knowledge is an important step in the rising use of graphene foam for biomedical applications,” he said.

Estrada believes the biomedical use of graphene foam may have other applications, including in the military where a majority combat injuries involve the musculoskeletal system. “Our vision is to develop novel bioscaffolds that can expedite healing, reduce the need for amputation, and help save lives,” he added.

Source: https://news.boisestate.edu/

A work led by SISSA in Italy and published on Nature Nanotechnology reports for the first time experimentally the phenomenon of ion ‘trapping’ by graphene carpets and its effect on the communication between neurons.The researchers have observed an increase in the activity of nerve cells grown on a single layer of graphene. Combining theoretical and experimental approaches they have shown that the phenomenon is due to the ability of the material to ‘trap’ several ions present in the surrounding environment on its surface, modulating its composition.

Graphene is the thinnest bi-dimensional material available today, characterisedby incredible properties of conductivity, flexibility and transparency. Although there are great expectations for its applications in the biomedical field, only very few works have analysed its interactions with neuronal tissue.
A study conducted by SISSA – Scuola Internazionale Superiore di Studi
Avanzati, and the University of Trieste in association with the University of Antwerp (Belgium), the Institute of Science and Technology of Barcelona (Spain), has analysed the behaviour of neurons grown on a single layer of graphene, observing a strengthening in their activity. Through theoretical and experimental approaches the researchers have shown that such behaviour is due to reduced ion mobility, in particular of potassium, to the neuron-graphene interface. This phenomenon is commonly called ‘ion trapping’, already known at theoretical level, but observed experimentally for the first time only now.

“It is as if graphene behaves as an ultra-thin magnet on whose surface some of the potassium ions present in the extra cellular solution between the cells and the graphene remain trapped.
It is this small variation that determines the increase in neuronal excitability” comments Denis Scaini, researcher at SISSA who has led the research alongside Laura Ballerini.
The study has also shown that this strengthening occurs when the graphene itself is supported by an insulator, like glass, or suspended in solution, while it disappears when lying on a conductor. “Graphene is a highly conductive material which could potentially be used to coat any surface. Understanding how its behaviour varies according to the substratum on which it is laid is essential for its future applications, above all in the neurological field” continues Scaini, “considering the unique properties of graphene it is natural to think for example about the development of innovative electrodes of cerebral stimulation or visual devices“.

Source: https://www.sissa.it/