Understanding Alzheimer’s: Study gives insights into how disease kills brain cells

Exactly how Alzheimer’s disease kills brain cells is still somewhat of a mystery, but University of Michigan researchers have uncovered a clue that supports the idea that small proteins prick holes into neurons.

The team also found that a certain size range of clumps of these proteins are particularly toxic to cells, while smaller and larger aggregates of the protein appear to be benign.

The findings, which appear in the journal PLOS ONE, add important detail to the knowledge base regarding this disease that affects 5.4 million Americans in 2012 but remains incurable and largely untreatable. The results could potentially help pharmaceutical researchers target drugs to the right disease mechanisms.

Small proteins called amyloid-beta peptides are the prime suspect for causing cell death in Alzheimer’s. They make up most of the senile plaque fibers found in the brains of autopsied patients. Researchers offer several hypotheses for how the peptides might cause the disease. They blame inflammation, oxidative stress or an imbalance of calcium ions possibly caused by holes in the cell membranes.

The U-M findings strongly support the idea that amyloid peptides damage the membrane around nerve cells and lead to uncontrolled movement of calcium ions into them. Calcium signaling is an important way that cells communicate and healthy cells regulate its flow precisely. The toxic mechanism implicated in the new study could act on its own or together with the other proposed courses and ultimately lead to a loss of brain cells in patients, the researchers say.

Calcium reveals connections between neurons

A team led by MIT neuroscientists has developed a way to monitor how brain cells coordinate with each other to control specific behaviors, such as initiating movement or detecting an odor.

The researchers’ new imaging technique, based on the detection of calcium ions in neurons, could help them map the brain circuits that perform such functions. It could also provide new insights into the origins of autism, obsessive-compulsive disorder and other psychiatric diseases, says Guoping Feng, senior author of a paper appearing in the Oct. 18 issue of the journal Neuron.

“To understand psychiatric disorders we need to study animal models, and to find out what’s happening in the brain when the animal is behaving abnormally,” says Feng, the James W. and Patricia Poitras Professor of Neuroscience and a member of the McGovern Institute for Brain Research at MIT. “This is a very powerful tool that will really help us understand animal models of these diseases and study how the brain functions normally and in a diseased state.”

Berkeley Lab scientists surprised to find significant adverse effects of CO2 on human decision-making performance.

Overturning decades of conventional wisdom, researchers at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) have found that moderately high indoor concentrations of carbon dioxide (CO₂) can significantly impair people’s decision-making performance. The results were unexpected and may have particular implications for schools and other spaces with high occupant density.

“In our field we have always had a dogma that CO₂ itself, at the levels we find in buildings, is just not important and doesn’t have any direct impacts on people,” said Berkeley Lab scientist William Fisk, a co-author of the study, which was published in Environmental Health Perspectives online last month. “So these results, which were quite unambiguous, were surprising.” The study was conducted with researchers from State University of New York (SUNY) Upstate Medical University.

On nine scales of decision-making performance, test subjects showed significant reductions on six of the scales at CO₂ levels of 1,000 parts per million (ppm) and large reductions on seven of the scales at 2,500 ppm. The most dramatic declines in performance, in which subjects were rated as “dysfunctional,” were for taking initiative and thinking strategically. “Previous studies have looked at 10,000 ppm, 20,000 ppm; that’s the level at which scientists thought effects started,” said Berkeley Lab scientist Mark Mendell, also a co-author of the study. “That’s why these findings are so startling.”

Read more: Elevated Indoor Carbon Dioxide Impairs Decision-Making Performance

moderation:

Eye-contact detector found in the brain

—

Why does making direct eye contact with someone give you that feeling of a special connection? Perhaps because it excites newly discovered “eye cells” in the amygdala, the part of the brain that processes emotions and social interactions.

This new type of neuron was discovered in a Rhesus macaque. If humans have these neurons too, it may be that they are impaired in disorders such as autism and schizophrenia, which affect eye contact and social interactions.

Katalin Gothard, a neurophysiologist at the University of Arizona in Tucson, and her team placed seven electrodes in the amygdala of a Rhesus macaque. The electrodes, each one-tenth the thickness of a human hair, allowed them to record activity in individual neurons as the macaque watched a video featuring another macaque. All the while, the team also tracked the macaque’s gaze.

Out of the 151 neurons the researchers could distinguish, 23 fired only when the macaque was looking at the eyes of the monkey in the video. Of these neurons, which the team call “eye cells”, four fired more when the monkey in the video appeared to be gazing back at the laboratory macaque, as if the two animals were making eye contact.

(via newscientist)

ucsdhealthsciences:

Fetal human neural stem cells stained for DNA (blue), neuronal (green) and astrocyte (red) markers. Image courtesy of Corey Seehus, GE Healthcare.

Brain gain

One of the enduring themes of Stem Cell Awareness Day is that while the potential is huge, the path to real-world achievement (i.e. effective treatments) is long and bumpy. There will be more failures than successes. We’re not there yet.

Nonetheless, a couple of recent events are reminders that progress is being made.

This week, researchers at the Oregon Health & Sciences University with colleagues elsewhere published a study in which they successfully implanted neural stem cells (capable of developing into any type of brain cell) in the brains of mice. More dramatically, scientists at UC San Francisco reported the implantation of neural stem cells into the brains of four boys with Pelizaeus-Merzbacher disease, a rare neurological disorder that impacts motor abilities, coordination and cognitive function. Both studies were published in Science Translational Medicine.

In the Oregon mouse study, the implanted neural stem cells changed into oligodendrocytes, a type of brain cell that produces myelin, which is used as insulating material to sheathe nerve fibers and improved inter-cell communications.

In the UCSF study, three of the four boys showed small but measurable improvement in motor function. None of the boys showed any adverse effects from the treatment.

These experiments follow news last month out of Mark Tuszynski’s lab at UC San Diego in which he and colleagues described “an astonishing degree” of axonal growth at the site of severe spinal cord injuries in rats. The research, according to Debra Kain’s report “revealed that early stage neurons have the ability to survive and extend axons to form new, functional neuronal relays across an injury site in the adult central nervous system.”

Like the other studies, Tuszynski used neural stem cells to effect repairs on what has, until now, always been perceived as irreparable. He embedded stem cells in a matrix of fibrin (a protein) mixed with neural growth factors. The resulting gel was then applied to the injury site in rats with completely severed spinal cords.

After six weeks, the number of axons emerging from the injury site was 200-fold more than anything recorded previously and the rats recovered some ability to move.

None of these studies, of course, are ends unto themselves, but, like the rats in Tuszynski’s experiments, they are tiny steps forward.

backyardpolitics:

The Long, Strange Journey of Einstein’s Brain : NPR

Albert Einstein died 50 years ago Monday. While that day marked the end of his life, it was only the beginning of a long, strange journey for his brain.

Thomas Harvey, a doctor at the hospital where Einstein died, removed the famous scientist’s brain and kept it with him over the next four decades. Harvey wanted to know what made Einstein a genius.

As Brian Burrell writes in his new book Postcards from the Brain Museum, Harvey wasn’t alone.

Scientists have long sought to understand the nature of genius and before computers and imaging technology, they had few options other than studying the actual brain.

Burrell discusses the long, strange journey of Einstein’s brain.

read more (via @gkbeg)

Abnormal Involuntary Eye Movements in the “Lazy Eye” Disease Amblyopia Linked to Changes in Subcortical Regions of the Brain

The neural mechanism underlying amblyopia, also called “lazy eye” is still not completely clear. A new study now reports abnormal eye movements of the lazy eye, which suggests that disturbed functioning of eye movement coordination between both eyes and not primarily the dysfunction of the visual cortex may be a cause of amblyopia (Xue-feng Shi et al.).

Little is known about oculomotor function in amblyopia, or “lazy eye,” despite the special role of eye movements in vision. A group of scientists has discovered that abnormal visual processing and circuitry in the brain have an impact on fixational saccades (FSs), involuntary eye movements that occur during fixation and are important for the maintenance of vision. The results, which raise the question of whether the alterations in FS are the cause or the effect of amblyopia and have implications for amblyopia treatment, are available online in advance of publication in the November issue of Restorative Neurology and Neuroscience.

“Although FSs are of great functional significance in neural coding, visual perception, and visual task execution, their behavioral characteristics in visual and neurological disease have been rarely studied,” says lead investigator Xue-Feng F. Shi, MD, PhD, of the Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, College of Clinical Ophthalmology, Tianjin Medical University, and the Department of Pediatric Ophthalmology and Strabismus, Tianjin Eye Hospital, Tianjin, China. “We carried out quantitative and detailed analysis of fixational saccades in amblyopia for the first time.”