The brain’s complex network of neurons enables us to interpret and effortlessly navigate and interact with the world around us. But when these links are damaged due to injury or stroke, critical tasks like perception and movement can be disrupted. New research is helping scientists figure out how to harness the brain’s plasticity to rewire these lost connections, an advance that could accelerate the development of neuro-prosthetics.
A new study authored by Marc Schieber, M.D., Ph.D., and Kevin Mazurek, Ph.D. with the University of Rochester Medical Center Department of Neurology and the Del Monte Institute for Neuroscience, which appears today in the journal Neuron, shows that very low levels of electrical stimulation delivered directly to an area of the brain responsible for motor function can instruct an appropriate response or action, essentially replacing the signals we would normally receive from the parts of the brain that process what we hear, see, and feel.
“The analogy is what happens when we approach a red light,” said Schieber. “The light itself does not cause us to step on the brake, rather our brain has been trained to process this visual cue and send signals to another parts of the brain that control movement. In this study, what we describe is akin to replacing the red light with an electrical stimulation which the brain has learned to associate with the need to take an action that stops the car.”
Drug designers working on therapeutics against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons, according to a new study in the journal Cell Reports.
In multiple sclerosis, immune cells degrade the insulation that protects neurons and allows them to signal to one another, but little is known about how immune cells penetrate the blood-brain barrier to get to neurons. Researchers led by Sarah Lutz, University of Illinois at Chicago College of Medicine while she was a post-doctoral fellow of Dritan Agalliu at Columbia University; and Sunil Gandhi, University of California, Irvine, have uncovered two different ways immune cells gain access to neurons and wreak their havoc.
Multiple sclerosis is a neurodegenerative inflammatory disease that affects approximately 2.5 million people worldwide. Immune cells turn against the body and cause damage to the myelin sheath, which encases neurons like the insulation on a wire. Loss of myelin interferes with the transmission of signals along the nerve fibers and impairs motor function, including walking and speech. Symptoms, which can be sporadic or progressive, range from mild to debilitating.
While researchers have known that two different kinds of immune cells, Th1 and Th17 lymphocytes, are involved in degrading myelin around neurons in multiple sclerosis, they didn’t know exactly how these cells crossed the blood-brain barrier to access neurons.
The blood-brain barrier is a bit of a misnomer. It not only protects the brain, but also the spine, and refers to the fact that blood vessels that supply the brain and spine are virtually impermeable because the cells that make up those blood vessels — called endothelial cells — are bolted tightly together by protein complexes called tight junctions. This prevents certain chemicals, harmful microbes and cells that circulate in the blood from gaining access to the brain and spine. In blood vessels that supply other organs of the body, endothelial cells are more loosely bound to one another and the connections can be adjusted to allow for the exchange of molecules and cells from the bloodstream into tissues and vice versa.
“In autoimmune diseases like multiple sclerosis, immune cells that enter the brain and spinal cord cause disease,” said Lutz, assistant professor of anatomy and cell biology in the UIC College of Medicine and the lead author of the paper. “A better understanding of how these cells cross the blood-brain barrier will aid our efforts to develop specific therapies to keep them out.”
To explore how Th1 and Th17 immune cells gain access to neurons in multiple sclerosis, Lutz and her colleagues looked at the blood-brain barrier in mice with experimental autoimmune encephalomyelitis — a mouse version of multiple sclerosis.
Researchers at King’s College London have discovered new mechanisms of cell death, which may be involved in debilitating neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease.
This novel research, published today in Current Biology, could lead to new therapeutic approaches for treating or delaying the progression of neurodegenerative conditions that are currently incurable, if the findings are expanded. Many current treatments for neurodegenerative conditions actually aim to enhance cell clearance, which may worsen rather than improve neurodegenerative symptoms, making the need for new treatment strategies an urgent priority.
Approximately 10 million people in the UK live with a neurological condition, with dementia alone estimated to cost the economy more than £10.5 billion per year in health and social care. Neurodegenerative conditions are characterised by a progressive loss of brain function, so that patients start to lose control of their movement, balance, memory and speech – similar to what happens when people have strong alcohol intoxication.
However, it is not currently known how or why these brain cells lose function, particularly in the terminal stage of these illnesses.
Using two animal models of a degenerative neurological disorder, the researchers were able to find a similar dysfunctional process occurring in fruit flies and mice, as well as human cells, meaning that their findings are likely to be replicated in human brains. Specifically, they found that in this condition nerve cells in certain areas of the brain become stalled and are no longer able to remove toxins or old and dysfunctional brain cells, which is a naturally occurring process known as autophagy. Autophagy is essentially how the brain breaks down cellular waste to elementary pieces, which are then recycled and used to construct and renovate brain cells.
The persistent stall in autophagy means the nerve cells are unable to ‘clean’ the brain and this results in a build up of toxins. Essentially the cells become confused and begin pushing out essential inner components rather than waste, leading to a loss of function and ultimately their death.
This new insight into how nerve cells might die from self-digestion has important implications for therapeutic approaches targeting autophagy. While current treatments aim to enhance cell clearance, in this study the authors were able to disrupt specific processes that interfere with cell clearance.
In a new study, researchers from Boston University School of Medicine (BUSM) describe a unique model for the biology of Alzheimer’s disease (AD) which may lead to an entirely novel approach for treating the disease. The findings appear in the journal Nature Neuroscience.
AD is a major cause of disease in the elderly and places a huge financial cost on the health care system. Scientists have known for a long time that two proteins (beta-amyloid and tau) clump and accumulate in the brains of Alzheimer patients, and this accumulation is thought to cause nerve cell injury that results in dementia.
Recent work by these BUSM researchers has shown that the clumping and accumulation of tau occurs as a normal response to stress, producing RNA/protein complexes termed “stress granules,” which reflect the need for the brain to produce protective proteins. The persistence of this “stress response” leads to excessive stress, the accumulation of pathological stress granules, and the accumulation of clumped tau, which drives nerve cell injury and produces dementia.
In the current study, the researchers use this new model and show that reducing the level of stress granule proteins yields strong protection, possibly by reducing persistent pathological stress granules as well as changing the type of tau clumping that occurs.
The team hypothesized that they could delay the disease process by reducing stress granules and decreasing this persistent stress response by genetically decreasing TIA1, which is a protein that is required for stress granule formation. Reducing TIA1 improved nerve cell health and produced striking improvements in memory and life expectancy in an experimental model of AD.