Non-Invasive Mapping Helps to Localize Language Centers Before Brain Surgery

A new functional magnetic resonance imaging (fMRI) technique may provide neurosurgeons with a non-invasive tool to help in mapping critical areas of the brain before surgery, reports a study in the April issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

Evaluating brain fMRI responses to a “single, short auditory language task” can reliably localize critical language areas of the brain—in healthy people as well as patients requiring brain surgery for epilepsy or tumors, according to the new research by Melanie Genetti, PhD, and colleagues of Geneva University Hospitals, Switzerland.

Brief fMRI Task for Functional Brain Mapping
The researchers designed and evaluated a quick and simple fMRI task for use in functional brain mapping. Functional MRI can show brain activity in response to stimuli (in contrast to conventional brain MRI, which shows anatomy only). Before neurosurgery for severe epilepsy or brain tumors, functional brain mapping provides essential information on the location of critical brain areas governing speech and other functions.

The standard approach to brain mapping is direct electrocortical stimulation (ECS)—recording brain activity from electrodes placed on the brain surface. However, this requires several hours of testing and may not be applicable in all patients. Previous studies have compared fMRI techniques with ECS, but mainly for determining the side of language function (lateralization) rather than the precise location (localization).

The new fMRI task was developed and evaluated in 28 healthy volunteers and in 35 patients undergoing surgery for brain tumors or epilepsy. The test used a brief (eight minutes) auditory language stimulus in which the patients heard a series of sense and nonsense sentences.

Functional MRI scans were obtained to localize the brain areas activated by the language task—activated areas would “light up,” reflecting increased oxygenation. A subgroup of patients also underwent ECS, the results of which were compared to fMRI.

Non-invasive Test Accurately Localizes Critical Brain Areas
Based on responses to the language stimulus, fMRI showed activation of the anterior and posterior (front and rear) language areas of the brain in about 90 percent of subjects—neurosurgery patients as well as healthy volunteers. Functional MRI activation was weaker and the language centers more spread-out in the patient group. These differences may have reflected brain adaptations to slow-growing tumors or longstanding epilepsy.

Five of the epilepsy patients also underwent ECS using brain electrodes, the results of which agreed well with the fMRI findings. Two patients had temporary problems with language function after surgery. In both cases, the deficits were related to surgery or complications (bleeding) in the language area identified by fMRI.

Functional brain mapping is important for planning for complex neurosurgery procedures. It provides a guide for the neurosurgeon to navigate safely to the tumor or other diseased area, while avoiding damage to critical areas of the brain. An accurate, non-invasive approach to brain mapping would provide a valuable alternative to the time-consuming ECS procedure.

"The proposed fast fMRI language protocol reliably localized the most relevant language areas in individual subjects," Dr. Genetti and colleagues conclude. In its current state, the new test probably isn’t suitable as the only approach to planning surgery—too many areas "light up" with fMRI, which may limit the surgeon’s ability to perform more extensive surgery with necessary confidence. The researchers add, "Rather than a substitute, our current fMRI protocol can be considered as a valuable complementary tool that can reliably guide ECS in the surgical planning of epileptogenic foci and of brain tumors."

A Sleep Aid Without the Side Effects

Insomniacs desperate for some zzzs may one day have a safer way to get them. Scientists have developed a new sleep medication that has induced sleep in rodents and monkeys without apparently impairing cognition, a potentially dangerous side effect of common sleep aids. The discovery, which originated in work explaining narcolepsy, could lead to a new class of drugs that help people who don’t respond to other treatments.

Between 10% and 15% of Americans chronically struggle with getting to or staying asleep. Many of them turn to sleeping pills for relief, and most are prescribed drugs, such as zolpidem (Ambien) and eszopiclone (Lunesta), that slow down the brain by binding to receptors for GABA, a neurotransmitter that’s involved in mood, cognition, and muscle tone. But because the drugs target GABA indiscriminately, they can also impair cognition, causing amnesia, confusion, and other problems with learning and memory, along with a number of strange sleepwalking behaviors, including wandering, eating, and driving while asleep. This has led many researchers to seek out alternative mechanisms for inducing sleep.

Neuroscientist Jason Uslaner of Merck Research Laboratories in West Point, Pennsylvania, and colleagues decided to tap into the brain’s orexin system. Orexin (also known as hypocretin) is a protein that controls wakefulness and is missing in people with narcolepsy. Past studies successfully induced sleep by inhibiting orexin, but had not looked into its effects on cognition. The researchers developed a new orexin-inhibiting compound called DORA-22 and confirmed that it could induce sleep in rats and rhesus monkeys as effectively as the GABA-modulating drugs.

Then the researchers went about testing the drugs’ effects on the animals’ cognition. They measured the rats’ cognition and memory by assessing the rodents’ ability to recognize objects. They presented the rats with a new object—say, a cone or a sphere—that the rats then sniffed and explored. Then they took the object away for an hour. After that hour, the rats were exposed to a new object and the one they’d already gotten to know; if the rats remembered, they spent less time checking out the familiar object. With the primates, Uslaner’s team tested their ability to match colors on a touchscreen and to pay attention to and identify the origin of a flashing light. In all the cases, the researchers found the GABA-modulating sleeping pills caused both the rats and the primates to respond more slowly and less accurately. Monkeys taking the memory and attention tests, for example, were 20% less accurate on the highest dose of each of the GABA-modulating drugs. But DORA-22 had no such effect on cognition, the team reports today in Science Translational Medicine.

"We were very excited," Uslaner says. "Folks who take sleep medications need to be able to perform cognitive tasks when they awake, and this [compound] could help them do so without impairment."

Although DORA-22 has not yet been tested in humans, it holds tremendous promise for helping people suffering from sleep disorders, says Emmanuel Mignot, a sleep researcher with the Stanford University School of Medicine in Palo Alto, California. “This study is encouraging and exciting, because there’s good reason to believe it would work differently from what we’ve used in the past,” says Mignot, who helped discover the link between orexin (or its absence) and narcolepsy. “Not every drug works for everyone, so it’s really, really good news to have a potential new drug on the horizon.”

Our internal clocks can become ticking time bombs for diabetes and obesity

New research in The FASEB Journal using mice suggests that disrupting our internal clocks can lead to a complete absence of 24-hour bodily rhythms and an immediate gain in body weight

If you’re pulling and all-nighter to finish a term paper, a new parent up all night with a fussy baby, or simply can’t sleep like you once could, then you may be snoozing on good health. That’s because new research published in The FASEB Journal used mice to show that proper sleep patterns are critical for healthy metabolic function, and even mild impairment in our circadian rhythms can lead to serious health consequences, including diabetes and obesity.

"We should acknowledge the unforeseen importance of our 24-hour rhythms for health," said Claudia Coomans, Ph.D., a researcher involved in the work from the Department of Molecular Cell Biology in the Laboratory of Neurophysiology at Leiden University Medical Center in Leiden, Netherlands. "To quote Seneca ‘We should live according to nature (secundum naturam vivere).’"

To make this discovery, Coomans and colleagues exposed mice to constant light, which disturbed their normal internal clock function, and observed a gradual degradation of their bodies’ internal clocks until it reached a level that normally occurs when aging. Eventually the mice lost their 24-hour rhythm in energy metabolism and insulin sensitivity, indicating that relatively mild impairment of clock function had severe metabolic consequences.

"The good news is that some of us can ‘sleep it off’ to avoid obesity and diabetes," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "The bad news is that we can all get the metabolic doldrums when our normal day/night cycle is disrupted."

Comparing mouse and human immune systems

It is a familiar note struck when authors conclude their reports on experiments conducted in mouse models: They suggest caution when translating their findings from mouse to human. A variation of this refrain can be heard when a small molecule that works in mice fails in human clinical trials.

There may be myriad reasons why results differ, and some challenges to the relevance of mouse models to human disease and therapy may be more anecdotal than evidence-driven, scientists say. But the need for better understanding the differences and similarities between human and mouse is clear. Genomic tools and analysis have opened the door to making comprehensive comparisons at a basic level that can inform future research in both mice and humans.

Scientists studying cell differentiation and function in the immune system set out to chart how the mouse and human compare in this area. Tal Shay, a postdoctoral associate in Aviv Regev’s lab at the Broad Institute of Harvard and MIT, led a team from Harvard Medical School, the Broad and Stanford University who compared two large compendia containing transcriptional profiles—how genes are expressed—in human and mouse immune cell types.

The researchers found remarkable consistency between gene expression profiles in the mouse and human immune systems but also some instances of divergence. The majority of gene expression patterns—conservatively estimated at 80 percent—were the same in mouse and human. In addition, they suggest a role for transcriptional regulators that may guide some of the similarities.

Shay and her colleagues reported their findings in PNAS and also deposited their data and analysis in a web portal, which they hope will serve as a reference map for other investigators. Their work is part of the ImmGen Consortium, a collaboration of immunologists and computational biologists generating a complete compendium of gene expression and its regulation in the mouse immune system.

“We wanted to pinpoint where immune system genes and gene expression are different and where you should be very suspicious if something is found in mouse and likely to be translated to human,” said Shay, who is a lead author of the paper. “We thought we might be able to map those places where the comparison is less robust, but we had a very hard time pinpointing convincing differences.”

The researchers had to take extraordinary pains to make sure they were comparing only what was comparable—apples to apples. Not all mouse genes had a corresponding gene in the human data set, or they had more than one: There might be one gene in humans versus five in mice for smell receptors, for example. Sometimes differences were a matter of timing: Genes were activated earlier or later, depending on the species, said David Puyraimond-Zemmour, an HMS graduate student in immunology in the lab of Christophe Benoist and Diane Mathis and a co-author of the PNAS paper.

In all, they found several dozen genes in seven immune cell types that have different expression in 80 human and 137 mouse samples. Their conclusions are based on comparing data from the Differentiation Map—which measures gene expression in about 40 human cell types—and data from ImmGen, which does the same for about 200 mouse cell types. They did further analyses of gene expression when cells were activated in different states, such as responding to infection, based on a data set produced by Ei Wakamatsu and Ting Feng, postdoctoral fellows in the Benoist-Mathis lab. Shay also worked with the Differentiation Map data from the lab of Benjamin Ebert, HMS associate professor of medicine at Brigham and Women’s Hospital and Dana-Farber Cancer Institute and an associate member of the Broad Institute, as well as from the ImmGen Project.

“What we assume most people will be interested in knowing is, if they are working on gene X, whether gene X has the same expression pattern in human and mouse immune systems,” Shay said. “Most lineages have the same expression signature but some genes behave differently and we think it’s important for why some things work in mice but not humans and the other way around.”

Benoist, Morton Grove-Rasmussen Professor of Immunohematology at Harvard Medical School, said the continuing debate about the usefulness of mouse models in understanding humans “is often at the level of the emotional and not necessarily very informed.” Wildly different experimental conditions—hugely varying doses or duration in clinical trials—make comparisons suspect, he said.

Having clear data that scientists can freely access will be useful, said Benoist, who is also a co-author of the PNAS paper.

“The value here is putting up signposts, signaling when the function of a gene in mice may not be relevant to humans,” he said, referring to data and analysis from the work published in PNAS. “Because the differentiation and function of human and mouse lineages are highly related, there is the expectation of conservation, so it is important to know when inter-species inferences may be an issue. Mouse models are far too valuable to be jettisoned for pre-clinical exploration, but it is important to know when caution is needed.”

New Research on the Effects of Traumatic Brain Injury (TBI)

Considerable opportunity exists to improve interventions and outcomes of traumatic brain injury (TBI) in older adults, according to three studies published in the recent online issue of NeuroRehabilitation by researchers from the Icahn School of Medicine at Mount Sinai.

An Exploration of Clinical Dementia Phenotypes Among Individuals With and Without Traumatic Brain Injury

Some evidence suggests that a history of TBI is associated with an increased risk of dementia later in life, but the clinical features of dementia associated with TBI have not been well investigated.  Researchers at the Icahn School of Medicine as well as other institutions analyzed data from elderly individuals with dementia with and without a history of TBI to characterize the clinical profiles of patients with post-TBI dementia.

The results of the study indicate that compared to older adults with dementia with no history of TBI, those with a history of TBI had higher fluency and verbal memory scores and later onset of decline. However, their general health was worse, they were more likely to have received medical attention for depression, and were more likely to have a gait disorder, falls, and motor slowness.  These findings suggest that dementia among individuals with a history of TBI may represent a unique clinical phenotype that is distinct from that seen among elderly individuals who develop dementia without a history of TBI.

"Our study indicates that individuals with dementia and without a history of TBI may present clinical characteristics that differ in subtle but meaningful ways," said Kristen Dams-O’Connor, PhD, first author of the study and an Assistant Professor of Rehabilitation Medicine at the Icahn School of Medicine at Mount Sinai. "It is imperative that clinicians take a history of TBI into account when making dementia diagnoses."

For this study, researchers used data from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) collected between September 2005 and May 2012 to analyze 332 elderly individuals with dementia and a history of TBI and 664 elderly individuals without dementia who do have a history of TBI. Statistical analyses focused on evaluating differences in the areas of neurocognitive functioning, psychiatric functioning, medical history and health, clinical characteristics of dementia, and dementia diagnosis using data collected at the baseline (first) NACC study visit.

Mortality of Elderly Individuals with TBI in the First 5 Years Following Injury

After observing a high rate of mortality among patients over the age of 55 in the first five years after sustaining a TBI, researchers at the Icahn School of Medicine at Mount Sinai were interested in learning more about the precise causes for what may be considered a premature death.

The results of this study indicate that for approximately a third of the patients, death one to five years after TBI resulted from health conditions that were present at the time of injury before the onset of TBI, suggesting a continuation of an already ongoing process. The remainder of patients died from conditions that appeared to unfold in the years after injury. According to the authors, each cause of death in this sample would have required pro-active medical management, medical intervention and medication compliance.

"Like those with other chronic health conditions, individuals with TBI could benefit from the development of a disease management model of primary care," said one of the study authors, Wayne Gordon, PhD, Jack Nash Professor and Vice Chair of the Department of Rehabilitation Medicine at the Icahn School of Medicine at Mount Sinai and Chief of the Rehabilitation Psychology and Neuropsychology service. "This study suggests that close medical management and lifestyle interventions may help to prevent premature death among elderly survivors of TBI in the future."

Researchers reviewed the charts of 30 individuals over the age of 55 who completed inpatient acute rehabilitation during the period from 2003-2009 and who died one to four years after TBI, and then compared that data to a matched sample of 30 patients who did not die. They found that 53 percent of deceased subjects had been diagnosed with gait abnormalities, 32 percent were taking respiratory medications at admission, and 17 percent were taking respiratory medications at discharge. Compared to patients who survived several years after injury, deceased patients were discharged from the hospital with significantly more medications.

Inpatient Rehabilitation for Traumatic Brain Injury: The Influence of Age on Treatments and Outcomes

For this study, researchers analyzed the difference in treatment and outcomes between elderly and younger patients with TBI. They found that patients over 65 had lower brain injury severity and a shorter length of stay in acute care. Elderly patients also received fewer hours of rehabilitation therapy, due to a shorter length of stay, and fewer hours of treatment per day, especially from psychology and therapeutic recreation. They gained less functional ability during and after rehabilitation, and had a very high mortality rate.

"We know significantly more about the treatment received by adolescents and young adults with TBI than we do about those over 65," said Marcel Dijkers, PhD, lead author and Research Professor in the Department of Rehabilitation Medicine at Mount Sinai.  "Our data indicates that elderly people can be rehabilitated successfully, but it raises a number of questions. For instance: is the high mortality due to the TBI or is it the result of the continuation of a condition that began pre-TBI?"

The researchers analyzed data on 1,419 patients with TBI admitted to nine TBI rehabilitation inpatient programs across the country between 2009 and 2011. They collected data through abstracting of medical records, point-of-care forms completed by therapists, and interviews conducted three and nine months after discharge.

Innovative neurology text includes patient videos

Practical Neurology Visual Review, a powerful educational tool for mastering the clinical practice of neurologic diagnosis, is now available in a fully revised and updated Second Editon.

Co-authors are neurologists Jose Biller, MD, of Loyola University Chicago Stritch School of Medicine and Alberto J. Espay, MD, of the University of Cincinnati.

The book previously was known as Practical Neurology DVD Review. It includes online videos of 131 real-world scenarios, and more than 370 multiple-choice questions. QR codes in the book allow easy access to videos via smart phone scanning.

Neurological problems are increasing due to the growing elderly population. But current assessment formats for the education of resident doctors, fellows and medical students underemphasize bedside teaching, Biller and Espay write in the introduction. “Faculty members strained by the pressures of many competing demands may not be in a position to oversee trainees performing physical examinations during their training.”

Practical Neurology Visual Review provides new venues for teaching and learning the essentials of neurology. The videos show patients with both common and unusual neurological problems, ranging from very easy to extremely challenging. The videos are used to teach five fundamental principles of bedside neurology: description and localization of findings, differential diagnosis, evaluation, management and counseling. Each clinical vignette is accompanied by a succinct written discussion.

"This audiovisual electronic teaching format may be somewhat unorthodox," Biller and Espay write. "However, it is actually more effective in its approach because the technology lends itself to displaying the skills necessary for a physician to form a patient’s neurological diagnosis."

How Serotonin Receptors Can Shape Drug Effects from LSD to Migraine Medication

A team including scientists from The Scripps Research Institute (TSRI), the University of North Carolina at Chapel Hill and the Chinese Academy of Sciences has determined and analyzed the high-resolution atomic structures of two kinds of human serotonin receptor. The new findings help explain why some drugs that interact with these receptors have had unexpectedly complex and sometimes harmful effects.

“Understanding the structure-function of these receptors allows us to discover new biology of serotonin signaling and also gives us better ideas about what biological questions to probe in a more intelligent manner,” said TSRI Professor Raymond Stevens, who was a senior investigator for the new research. The studies were published in two papers on March 21, 2013 in Science Express [1 , 2], the advance online version of the journal Science.

Pioneering Important Molecular Structures

Stevens’s laboratory at TSRI has pioneered the development of techniques for determining the 3D atomic structures of cellular receptors—particularly the large receptor class known as G protein-coupled receptors (GPCRs). GPCRs sit in the cell membrane and sense various molecules outside cells. When certain molecules bind to them, the receptor’s respond in a way to transmit a signal inside the cell.

“Because G protein-coupled receptors are the targets of nearly 50 percent of medicines, they are the focus of several major National Institutes of Health (NIH) initiatives,” said Jean Chin of the NIH’s National Institute of General Medical Sciences, which partly funded the work through the Protein Structure Initiative. “These detailed molecular structures of two serotonin receptor subfamilies bound to antimigraines, antipsychotics, antidepressants or appetite suppressants will help us understand how normal cellular signaling is affected by these drugs and will offer a valuable framework for designing safer and more effective medicines.”

In the past several years, using X-ray crystallography, the Stevens laboratory has determined the high-resolution structures of 10 of the most important GPCRs for human health—including the β2 adrenergic receptor, the A2a adenosine receptor (the target of caffeine), HIV related CXCR4 receptor, the pain-mediating nociceptin receptor, S1P1 receptor important for inflammatory diseases, H1 histamine receptor (antihistamine medications) and the D3 dopamine receptor which is involved in mood, motivation and addiction.

Serotonin receptors are no less important. “Nearly all psychiatric drugs affect serotonin receptors to some extent, and these receptors also mediate a host of effects outside the brain, for example on blood coagulation, smooth muscle contraction and heart valve growth,” said Bryan Roth, a collaborator on both studies who is professor of pharmacology at the University of North Carolina (UNC).

Untangling Two Serotonin Receptors

Roth’s laboratory teamed up with Stevens’s as part of the National Institute of General Medical Sciences (NIGMS) Protein Structure Initiative. For this project the two labs also worked with the laboratories of Professors Eric Xu and Hualiang Jiang at the Shanghai Institute of Materia Medica, part of the Chinese Academy of Sciences. “By collaborating with the Chinese teams we were able to complete a much more thorough study and get the most out of our fundamental structural results,” said Stevens.

In the first of the new studies, co-lead author Chong Wang, a graduate student in the Stevens laboratory, and his colleagues determined the structure of the serotonin receptor subtype 5-HT_1B, the principal target of several drug classes. (5-HT, or 5-hydroxytryptamine, is a technical term for serotonin.) The team produced the 5-HT_1B receptor while it was bound by either ergotamine or dihydroergotamine—two old-line anti-migraine drugs that work in part by activating 5-HT_1B receptors.

With the help of the special fusion protein, nicknamed BRIL (apocytochrome b562RIL), Wang and colleagues were able to stabilize these structures and coax them to line up in a regular ordering known as a crystal. X-ray crystallography revealed, at high resolution, an atomic structure of 5-HT_1B with a main binding pocket and a separate, extended binding pocket.

Harmful Off-Target Effects

In the second study, TSRI graduate student and lead author Daniel Wacker and colleagues used similar techniques to determine the structure of the 5-HT_2B receptor bound to ergotamine. The 5-HT_2B receptor was chiefly of interest because drug developers want to avoid activating it.

“Drugs that are meant to target other serotonin receptors in the brain can have harmful off-target effects on 5-HT_2B receptors, which are found abundantly on heart valves, for example,” said Roth. The weight-loss drug fenfluramine and closely related dexfenfluramine were withdrawn from the US market in 1997 after being linked to heart valve disease. Roth’s laboratory later showed that this side effect was mediated by heart valve 5-HT_2B receptors.

Analyses of the 5-HT_1B and 5-HT_2B receptor structures revealed a subtle difference between them. “Although their main binding pockets look very similar, their extended binding pockets are not as similar—the one for 5-HT_2B is narrower and in a slightly different position,” said Wang.

With the two receptor structures in hand, the Xu and Jiang team simulated the bindings of various drugs. They showed, for example, that anti-migraine drugs called triptans should bind well to 5-HT_1B receptors but poorly to 5-HT_2B receptor structures, in which the extended binding pocket is less accessible. Similarly, the team’s calculations confirmed that fenfluramine’s active metabolite should bind very tightly to the 5-HT_2B receptor.

Delving Deeper

In the second study, the researchers used the 5-HT_2B and 5-HT_1B structural data to better understand a recently discovered GPCR signaling pathway.

When a neurotransmitter such as serotonin binds to its GPCR receptor and triggers the primary, G protein-mediated activation signal, it also usually triggers another signal, often mediated by a protein called β-arrestin. This second signaling cascade may simply have the effect of “arresting” or inhibiting the primary, G protein-mediated signaling. But it can also have other effects on the cell, and although most molecules bind to their target GPCRs in a way that activates these primary and secondary signals equally, others preferentially activate one or the other. “Such functional selectivity, as we call it, adds another layer of complexity to drug effects on GPCRs,” said Roth, a co-senior author of the study.

Roth’s laboratory produced several 5-HT receptor subtypes in test cells, and compared the strength of G-protein and β-arrestin signaling when these receptors were bound by ergotamine or various other drugs, including the ergotamine-derived hallucinogen LSD (lysergic acid diethylamide). Most of the tested drugs showed no bias. However, ergotamine, LSD and some of their relatives turned out to be clearly biased in favor of β-arrestin signaling at the 5-HT_2B receptor. Comparison of the ergotamine-bound 5-HT_2B structure with the ergotamine-bound 5-HT_1B structure revealed the likely reason. “We could see that when ergotamine is bound to the 5-HT_2B receptor it stabilizes the receptor structure in a conformation that interferes with G protein signaling,” said Wacker.

The findings allow scientists to start probing this arrestin-mediated signaling pathway and its downstream effects in a more targeted manner. “These structural data are teaching us to ask better questions about receptor biology,” said Stevens.

Stem Cell Research Could Expand Clinical Use of Regenerative Human Cells

Research led by a biology professor in the School of Science at IUPUI has uncovered a method to produce retinal cells from regenerative human stem cells without the use of animal products, proteins or other foreign substances, which historically have limited the application of stem cells to treat disease and other human developmental disorders.

The study of human induced pluripotent stem cells (hiPSCs) has been pursued vigorously since they were first discovered in 2007 due to their ability to be manipulated into specific cell types. Scientists believe these cells hold considerable potential for cell replacement, disease modeling and pharmacological testing. However, clinical applications have been hindered by the fact that, to date, the cells have required animal products and proteins to grow and differentiate

A research team led by Jason S. Meyer, Ph.D., assistant professor of biology, successfully differentiated hiPSCs in a lab environment—completely through chemical methods—to form neural retinal cell types (including photoreceptors and retinal ganglion cells). Tests have shown the cells function and grow just as efficiently as those cells produced through traditional methods.

“Not only were we able to develop these (hiPSC) cells into retinal cells, but we were able to do so in a system devoid of any animal cells and proteins,” Meyer said. “Since these kinds of stem cells can be generated from a patient’s own cells, there will be nothing the body will recognize as foreign.”

In addition, this research should allow scientists to better reproduce these cells because they know exactly what components were included to spur growth and minimize or eliminate any variations, Meyer said. Furthermore, the cells function in a very similar fashion to human embryonic stem cells, but without controversial or immune rejection issues because they are derived from individual patients.

“This method could have a considerable impact on the treatment of retinal diseases such as age-related macular degeneration and forms of blindness with hereditary factors,” Meyer said. “We hope this will help us understand what goes wrong when diseases arise and that we can use this method as platform for the development of new treatments or drug therapies.”

“We’re talking about bringing stem cells a significant step closer to clinical use,” Meyer added.

The research will be published in the April edition of Stem Cells Translational Medicine.

Hypertension Could Bring Increased Risk for Alzheimer’s disease

A study in the Journal of the American Medical Association Neurology suggests that controlling or preventing risk factors, such as hypertension, earlier in life may limit or delay the brain changes associated with Alzheimer’s disease and other age-related neurological deterioration.

Dr. Karen Rodrigue, assistant professor in the UT Dallas Center for Vital Longevity (CVL), was lead author of a study that looked at whether people with both hypertension and a common gene had more buildup of a brain plaque called amyloid protein, which is associated with Alzheimer’s disease. Scientists believe amyloid is the first symptom of Alzheimer’s disease and shows up a decade or more before symptoms of memory impairment and other cognitive difficulties begin. The gene, known as APOE 4, is carried by 20 percent of the population.

Until recently, amyloid plaque could be seen only at autopsy, but new brain scanning techniques allow scientists to see plaque in living brains of healthy adults. Findings from both autopsy and amyloid brain scans show that at least 20 percent of typical older adults carry elevated levels of amyloid, a substance made up mostly of protein that is deposited in organs and tissues.

“I became interested in whether hypertension was related to increased risk of amyloid plaques in the brains of otherwise healthy people,” Rodrigue said. “Identifying the most significant risk factors for amyloid deposition in seemingly healthy adults will be critical in advancing medical efforts aimed at prevention and early detection.”

Based on evidence that hypertension was associated with Alzheimer’s disease, Rodrigue suspected that the combination of hypertension and the presence of the APOE-e4 gene might lead to particularly high levels of amyloid plaque in healthy adults.