Posts tagged neuroscience
Articles and news from the latest research reports.
Study Finds No Link Between Hallucinogens And Mental Problems
How risky are psychedelic drugs to mental health? Not nearly as much as you might have imagined.
People who had taken LSD, psilocybin (the brain-bending chemical in magic mushrooms) or mescaline at any time in their lives were no more likely than those who hadn’t to wind up in mental health treatment or to have symptoms of mental illness, according to an analysis by some Norwegian researchers.
And there was some evidence that people who had taken the drugs at some point were less likely to have had recent mental health treatment.
"There seems to be no evidence of overall negative impact — and even some hints of benefit — associated with the use of psychedelics," says , a psychologist in the psychiatry department at Johns Hopkins School of Medicine.
Johnson wasn’t involved in the study but had read the work, which was by PLOS ONE. In separate human experiments, Johnson and his colleagues at Hopkins have given psilocybin to cancer patients under carefully controlled conditions to help them cope with anxiety and depression.
The latest study comes from researchers at the Norwegian University of Science and Technology who analyzed data from the , sponsored by the U.S. Substance Abuse and Mental Health Administration. Previously, the Norwegian researchers looked back at old data on and concluded that it wasn’t a bad idea at all.
In this study, the researchers looked at survey data collected from more than 130,000 randomly selected Americans between 2001 and 2004. Nearly 22,000, or about 13 percent, said they had taken hallucinogenic drugs at some point. About aged 21-64 have tried psychedelics.
"The lack of association between the use of psychedelics and indicators of mental health problems in this large population survey is consistent with clinical studies in which LSD or other psychedelics have been ," the researchers wrote.
This study has limitations. It’s possible that healthier people are more likely to take psychedelics than those already struggling with mental illness, for instance. The study also didn’t take the dose of drugs into account. The researchers also didn’t have any information about family history of mental illness, which could be an important factor.
"The design of our study does not allow conclusions about causality," Teri S. Krebs, the lead author of the study, wrote in an email to Shots. "However, there is a lack of evidence that psychedelics cause lasting mental health problems."
While the findings are broadly reassuring about the safety of hallucinogenic drugs, they don’t guarantee a good trip. “This should not be taken to state that there are never individual cases of harm. We know that there are,” Johnson says. “It’s a question of how frequent they are and under what circumstances they happen.”
Neurologists Report Unique Form of Musical Hallucinations
Case raises intriguing questions about memory and forgetting
One night when she was trying to fall asleep, a 60-year-old woman suddenly began hearing music, as if a radio were playing at the back of her head.
The songs were popular tunes her husband recognized when she sang or hummed them. But she herself could not identify them.
This is the first known case of a patient hallucinating music that was familiar to people around her, but that she herself did not recognize, according to Dr. Danilo Vitorovic and Dr. José Biller of Loyola University Medical Center. The neurologists describe the unique case in the journal Frontiers in Neurology.
The case raises “intriguing questions regarding memory, forgetting and access to lost memories,” the authors write.
Musical hallucinations are a form of auditory hallucinations, in which patients hear songs, instrumental music or tunes, even though no such music is actually playing. Most patients realize they are hallucinating, and find the music intrusive and occasionally unpleasant. There is no cure.
Musical hallucinations usually occur in older people. Several conditions are possible causes or predisposing factors, including hearing impairment, brain damage, epilepsy, intoxications and psychiatric disorders such as depression, schizophrenia and obsessive-compulsive disorder. Hearing impairment is the most common predisposing condition, but is not by itself sufficient to cause hallucinations.
Vitorovic and Biller describe a hearing-impaired patient who initially hallucinated music when she was trying to fall asleep. Within four months, she was hearing music all the time. For example, she would hear one song over and over for three weeks, then another song would begin playing. The volume never changed, and she was able to hear and follow conversations while hallucinating the music.
The patient was treated with carbamazepine, an anti-seizure drug, and experienced some improvement in her symptoms.
The unique feature of the patient was her ability to hum parts of some tunes and recall bits of lyrics from some songs that she did not even recognize. This raises the possibility that the songs were buried in her memory, but she could not access them except when she was hallucinating.
“Further research is necessary on the mechanisms of forgetfulness,” Vitorovic and Biller write. “In other words, is forgotten information lost, or just not accessible?”
(Image: Marten Blom)
First Pre-Clinical Gene Therapy Study to Reverse Rett Symptoms
The concept behind gene therapy is simple: deliver a healthy gene to compensate for one that is mutated. New research published today in the Journal of Neuroscience suggests this approach may eventually be a feasible option to treat Rett Syndrome, the most disabling of the autism spectrum disorders. Gail Mandel, Ph.D., a Howard Hughes Investigator at Oregon Health and Sciences University, led the study. The Rett Syndrome Research Trust, with generous support from the Rett Syndrome Research Trust UK and Rett Syndrome Research & Treatment Foundation, funded this work through the MECP2 Consortium.
In 2007, co-author Adrian Bird, Ph.D., at the University of Edinburgh astonished the scientific community with proof-of-concept that Rett is curable, by reversing symptoms in adult mice. His unexpected results catalyzed labs around the world to pursue a multitude of strategies to extend the pre-clinical findings to people.
Today’s study is the first to show reversal of symptoms in fully symptomatic mice using techniques of gene therapy that have potential for clinical application.
Rett Syndrome is an X-linked neurological disorder primarily affecting girls; in the US, about 1 in 10,000 children a year are born with Rett. In most cases symptoms begin to manifest between 6 and 18 months of age, as developmental milestones are missed or lost. The regression that follows is characterized by loss of speech, mobility, and functional hand use, which is often replaced by Rett’s signature gesture: hand-wringing, sometimes so intense that it is a constant during every waking hour. Other symptoms include seizures, tremors, orthopedic and digestive problems, disordered breathing and other autonomic impairments, sensory issues and anxiety. Most children live into adulthood and require round-the-clock care.
The cause of Rett Syndrome’s terrible constellation of symptoms lies in mutations of an X-linked gene called MECP2 (methyl CpG-binding protein). MECP2 is a master gene that regulates the activity of many other genes, switching them on or off.
“Gene therapy is well suited for this disorder,” Dr. Mandel explains. “Because MECP2 binds to DNA throughout the genome, there is no single gene currently that we can point to and target with a drug. Therefore the best chance of having a major impact on the disorder is to correct the underlying defect in as many cells throughout the body as possible. Gene therapy allows us to do that.”
Healthy genes can be delivered into cells aboard a virus, which acts as a Trojan horse. Many different types of these Trojan horses exist. Dr. Mandel used adeno-associated virus serotype 9 (AAV9), which has the unusual and attractive ability to cross the blood-brain barrier. This allows the virus and its cargo to be administered intravenously, instead of employing more invasive direct brain delivery systems that require drilling burr holes into the skull.
Because the virus has limited cargo space, it cannot carry the entire MECP2 gene. Co-author Brian Kaspar of Nationwide Children’s Hospital collaborated with the Mandel lab to package only the gene’s most critical segments. After being injected into the Rett mice, the virus made its way to cells throughout the body and brain, distributing the modified gene, which then started to produce the MeCP2 protein.
As in human females with Rett Syndrome, only approximately 50% of the mouse cells have a healthy copy of MECP2. After the gene therapy treatment 65% of cells now had a functioning MECP2 gene.
The treated mice showed profound improvements in motor function, tremors, seizures and hind limb clasping. At the cellular level the smaller body size of neurons seen in mutant cells was restored to normal. Biochemical experiments proved that the gene had found its way into the nuclei of cells and was functioning as expected, binding to DNA.
One Rett symptom that was not ameliorated was abnormal respiration. Researchers hypothesize that correcting this may require targeting a greater number of cells than the 15% that had been achieved in the brainstem.
“We learned a critical and encouraging point with these experiments – that we don’t have to correct every cell in order to reverse symptoms. Going from 50% to 65% of the cells having a functioning gene resulted in significant improvements,” said co-author Saurabh Garg.
One of the potential challenges of gene therapy in Rett is the possibility of delivering multiple copies of the gene to a cell. We know from the MECP2 Duplication Syndrome that too much of this protein is detrimental. “Our results show that after gene therapy treatment the correct amount of MeCP2 protein was being expressed. At least in our hands, with these methods, overexpression of MeCP2 was not an issue,” said co-author Daniel Lioy.
Dr. Mandel cautioned that key steps remain before clinical trials can begin. “Our study is an important first step in highlighting the potential for AAV9 to treating the neurological symptoms in Rett. We are now working on improving the packaging of MeCP2 in the virus to see if we can target a larger percentage of cells and therefore improve symptoms even further,” said Mandel. Collaborators Hélène Cheval and Adrian Bird see this as a promising follow up to the 2007 work showing symptom reversal in Rett mice. “That study used genetic tricks that could not be directly applicable to humans, but the AAV9 vector used here could in principle deliver a gene therapeutically. This is an important step forward, but there is a way to go yet.”
“Gene therapy has had a tumultuous road in the past few decades but is undergoing a renaissance due to recent technological advances. Europe and Asia have gene therapy treatments already in the clinic and it’s likely that the US will follow suit. Our goal now is to prioritize the next key experiments and facilitate their execution as quickly as possible. Gene therapy, especially to the brain, is a tricky undertaking but I’m cautiously optimistic that with the right team we can lay out a plan for clinical development. I congratulate the Mandel and Bird labs on today’s publication, which is the third to be generated from the MECP2 Consortium in a short period of time,” said Monica Coenraads, Executive Director of the Rett Syndrome Research Trust and mother of a teenaged daughter with the disorder.
(Source: rsrt.org)
![Building Better Brain Implants: The Challenge of Longevity
On August 20, JoVE, the Journal of Visualized Experiments will publish a technique from the Capadona Lab at Case Western Reserve University to accommodate two challenges inherent in brain-implantation technology, gauging the property changes that occur during implantation and measuring on a micro-scale. These new techniques open the doors for solving a great challenge for bioengineers — crafting a device that can withstand the physiological conditions in the brain for the long-term.
“We created an instrument to measure the mechanical properties of micro-scale biomedical implants, after being explanted from living animals,” explained the lab’s principal investigator, Dr. Jeffrey R. Capadona. By preserving the changing properties that occurred during implantation even after removal, the technique offers potential to create and test new materials for brain implant devices. It could result in producing longer lasting and better suited devices for the highly-tailored functions.
For implanted devices, withstanding the high-temperatures, moisture, and other in-vivo properties poses a challenge to longevity. Resulting changes in stiffness, etc, of an implanted material can trigger a greater inflammatory response. “Often, the body’s reaction to those implants causes the device to prematurely fail,” says Dr. Capadona, “In some cases, the patient requires regular brain surgery to replace or revise the implants.”
New implantation materials may help find solutions to restore motor function in individuals who have suffered from spinal cord injuries, stroke or multiple sclerosis. “Microelectrodes embedded chronically in the brain could hold promise for using neural activity to restore motor function in individuals who have, suffered from spinal cord injuries,” said Dr. Capadona.
Furthermore, Capadona and his colleagues’ method allows for measurement of mechanical properties using microsize scales. Previous methods typically require large or nano-sized samples of material, and data has to be scaled, which doesn’t always work.
When asked why Dr. Capadona and his colleagues published their methods with JoVE, he responded “We choose JoVE because of the novel format to show readers visually what we are doing. If a picture is worth [a] thousand words, a video is worth a million.”](http://41.media.tumblr.com/339c082c16372e9e4ff44d3f5528261e/tumblr_mrupbokuzM1rog5d1o1_500.png)
Building Better Brain Implants: The Challenge of Longevity
On August 20, JoVE, the Journal of Visualized Experiments will publish a technique from the Capadona Lab at Case Western Reserve University to accommodate two challenges inherent in brain-implantation technology, gauging the property changes that occur during implantation and measuring on a micro-scale. These new techniques open the doors for solving a great challenge for bioengineers — crafting a device that can withstand the physiological conditions in the brain for the long-term.
“We created an instrument to measure the mechanical properties of micro-scale biomedical implants, after being explanted from living animals,” explained the lab’s principal investigator, Dr. Jeffrey R. Capadona. By preserving the changing properties that occurred during implantation even after removal, the technique offers potential to create and test new materials for brain implant devices. It could result in producing longer lasting and better suited devices for the highly-tailored functions.
For implanted devices, withstanding the high-temperatures, moisture, and other in-vivo properties poses a challenge to longevity. Resulting changes in stiffness, etc, of an implanted material can trigger a greater inflammatory response. “Often, the body’s reaction to those implants causes the device to prematurely fail,” says Dr. Capadona, “In some cases, the patient requires regular brain surgery to replace or revise the implants.”
New implantation materials may help find solutions to restore motor function in individuals who have suffered from spinal cord injuries, stroke or multiple sclerosis. “Microelectrodes embedded chronically in the brain could hold promise for using neural activity to restore motor function in individuals who have, suffered from spinal cord injuries,” said Dr. Capadona.
Furthermore, Capadona and his colleagues’ method allows for measurement of mechanical properties using microsize scales. Previous methods typically require large or nano-sized samples of material, and data has to be scaled, which doesn’t always work.
When asked why Dr. Capadona and his colleagues published their methods with JoVE, he responded “We choose JoVE because of the novel format to show readers visually what we are doing. If a picture is worth [a] thousand words, a video is worth a million.”
New models advance the study of deadly human prion diseases
By directly manipulating a portion of the prion protein-coding gene, Whitehead Institute researchers have created mouse models of two neurodegenerative diseases that are fatal in humans. The highly accurate reproduction of disease pathology seen with these models should advance the study of these unusual but deadly diseases.
“By altering single amino acid codons in the gene coding for the prion protein, in the natural context of the genome—no over expression or other artificial manipulations—we can produce completely different neurodegenerative diseases, each of which spontaneously generates an infectious prion agent,” says Whitehead Member Susan Lindquist. “The work irrefutably establishes the prion hypothesis.”
According to the prion hypothesis, prion proteins infect by passing along their misfolded shape in templated fashion, unlike viruses or bacteria, which depend on DNA or RNA to transmit their information. Certain changes to the prion protein (PrP) create a misshapen structure, which is replicated by contact. The misfolded proteins accumulate, creating clumps that are toxic to surrounding tissue.
PrP is expressed at high levels in the brain, and prion diseases, including Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE, or “mad cow disease”) in cows, and scrapie in sheep, wreak havoc on the brain and other neural tissues. Some prion diseases, like BSE, can be transmitted from feed animals to humans.
The study of these highly unusual but devastating prion diseases has to date been thwarted by a lack of animal models that faithfully mimic the disease processes in humans. However, Walker Jackson, a former postdoctoral researcher in Lindquist’s lab is changing that, creating novel mouse models of human fatal familial insomnia (FFI) and CJD. His research is reported online this week in the Proceedings of the National Academy of Sciences (PNAS).
To generate the models, Jackson created two mutated versions of the PrP-coding gene by changing a single codon—one of the three-nucleotide “words” in genes that code for the various amino acids in proteins. One mutation is known to cause FFI, while the other induces CJD. Unlike previous models that randomly inserted the mutations into the genome, occasionally increasing PrP expression, Jackson’s models faithfully mimic the human disease—from as to disease onset, to PrP production, to infectiousness. In the brain, his FFI mice develop neuronal loss in the thalamus and his CJD mice experience spongiosis in the hippocampus and the cerebellum, reflecting the damage seen in the brains of human patients.
“Walker (Jackson)’s work provides two extraordinary models of neurodegeneration,” says Lindquist, who is also a professor of biology at MIT. “Most mouse models produce pathology that only distantly resembles human diseases. These nail it, for two of the most enigmatic human diseases in the world.”
With the FFI and CJD models in hand, Jackson says he’s excited to investigate how the pathology of these diseases develops.
“Now we have two interesting models that are selectively targeting specific parts of the brain: the thalamus in FFI and the hippocampus in CJD,” says Jackson, who is now a Group Leader at the German Center for Neurodegenerative Disease. “But instead of focusing on areas that are heavily affected by the disease, we’ll be looking at the areas that seem to be resisting the disease to see what they’re doing. The protein is there, but for some reason, it’s not toxic.”
Initial characterization of one of the models (for FFI) was reporter earlier in Neuron.
High-Flying Pilots at Increased Risk of Brain Lesions
A new study suggests that pilots who fly at high altitudes may be at an increased risk for brain lesions. The study is published in the August 20, 2013, print issue of Neurology®, the medical journal of the American Academy of Neurology.
For the study, 102 U-2 United States Air Force pilots and 91 non-pilots between the ages of 26 and 50 underwent MRI brain scans. The scans measured the amount of white matter hyperintensities, or tiny brain lesions associated with memory decline in other neurological diseases. The groups were matched for age, education and health factors.
“Pilots who fly at altitudes above 18,000 feet are at risk for decompression sickness, a condition where gas or atmospheric pressure reaches lower levels than those within body tissues and forms bubbles,” said study author Stephen McGuire, MD, with the University of Texas in San Antonio, the US Air Force School of Aerospace Medicine and a Fellow of the American Academy of Neurology. “The risk for decompression sickness among Air Force pilots has tripled from 2006, probably due to more frequent and longer periods of exposure for pilots. To date however, we have been unable to demonstrate any permanent clinical neurocognitive or memory decline.”
Symptoms affecting the brain that sometimes accompany decompression sickness include slowed thought processes, confusion, unresponsiveness and permanent memory loss.
The study found that pilots had nearly four times the volume and three times the number of brain lesions as non-pilots. The results were the same whether or not the pilots had a history of symptoms of decompression sickness.
The research also found that while the lesions in non-pilots were mainly found in the frontal white matter, as occurs in normal aging, lesions in the pilots were evenly distributed throughout the brain.
“These results may be valuable in assessing risk for occupations that include high-altitude mountain climbing, deep sea diving and high-altitude flying,” McGuire said.
Computer can read letters directly from the brain
By analysing MRI images of the brain with an elegant mathematical model, it is possible to reconstruct thoughts more accurately than ever before. In this way, researchers from Radboud University Nijmegen have succeeded in determining which letter a test subject was looking at. The journal Neuroimage has accepted the article, which will be published soon. A preliminary version of the article can be read online.
Functional MRI scanners have been used in cognition research primarily to determine which brain areas are active while test subjects perform a specific task. The question is simple: is a particular brain region on or off? A research group at the Donders Institute for Brain, Cognition and Behaviour at Radboud University has gone a step further: they have used data from the scanner to determine what a test subject is looking at. The researchers ‘taught’ a model how small volumes of 2x2x2 mm from the brain scans - known as voxels - respond to individual pixels. By combining all the information about the pixels from the voxels, it became possible to reconstruct the image viewed by the subject. The result was not a clear image, but a somewhat fuzzy speckle pattern. In this study, the researchers used hand-written letters.
Prior knowledge improves model performance
‘After this we did something new’, says lead researcher Marcel van Gerven. ‘We gave the model prior knowledge: we taught it what letters look like. This improved the recognition of the letters enormously. The model compares the letters to determine which one corresponds most exactly with the speckle image, and then pushes the results of the image towards that letter. The result was the actual letter, a true reconstruction.’
‘Our approach is similar to how we believe the brain itself combines prior knowledge with sensory information. For example, you can recognise the lines and curves in this article as letters only after you have learned to read. And this is exactly what we are looking for: models that show what is happening in the brain in a realistic fashion. We hope to improve the models to such an extent that we can also apply them to the working memory or to subjective experiences such as dreams or visualisations. Reconstructions indicate whether the model you have created approaches reality.’
Improved resolution; more possibilities
‘In our further research we will be working with a more powerful MRI scanner,’ explains Sanne Schoenmakers, who is working on a thesis about decoding thoughts. ‘Due to the higher resolution of the scanner, we hope to be able to link the model to more detailed images. We are currently linking images of letters to 1200 voxels in the brain; with the more powerful scanner we will link images of faces to 15,000 voxels.’
The Concussed Brain at Work: fMRI Study Documents Brain Activation During Concussion Recovery
For the first time, researchers have documented irregular brain activity within the first 24 hours of a concussive injury, as well as an increased level of brain activity weeks later—suggesting that the brain may compensate for the injury during the recovery time.
The findings are published in the September issue of the Journal of the International Neuropsychological Society
Thomas Hammeke, PhD, professor of psychiatry and behavioral medicine at the Medical College of Wisconsin, is the lead author. Collaborators at the Cleveland Clinic; St. Mary’s Hospital in Enid, Okl.; the University of North Carolina; Franklin College in Franklin, Ind., and the Marshfield Clinic in Marshfield, Wis., co-authored the paper.
To study the natural recovery from sports concussion, 12 concussed high school football athletes and 12 uninjured teammates were evaluated at 13 hours and again at seven weeks following concussive injury.
The concussed athletes showed the expected postconcussive symptoms, including decreased reaction time and lowered cognitive abilities. Imaging via fMRI (functional magnetic resonance imaging) showed decreased activity in select regions of the right hemisphere of the brain, which suggests the poor cognitive performance of concussion patients is related to that underactivation of attentional brain circuits.
Seven weeks post-injury, the concussed athletes showed improvement of cognitive abilities and normal reaction time. However, imaging at that time showed the post-concussed athletes had more activation in the brain’s attentional circuits than did the control athletes.
“This hyperactivation may represent a compensatory brain response that mediates recovery,” said Dr. Hammeke. “This is the first study to demonstrate that reversal in activation patterns, and that reversal matches the progression of symptoms from the time of the injury through clinical recovery.”
“Deciding when a concussed player should return to the playing field is currently an inexact science,” said Dr. Stephen Rao, director of the Schey Center for Cognitive Neuroimaging at the Cleveland Clinic and a senior author. “Measuring changes in brain activity during the acute recovery period can provide a scientific basis for making this critical decision.”
Each year, an estimated 3.8 million people sustain a traumatic brain injury (TBI). TBI is a contributing factor to a third of all injury-related deaths in the United States. More than three-quarters of the TBI’s that occur are concussions or other forms of mild TBI, many of which may go undiagnosed.
(Image: Corbis)
Brain network decay detected in early Alzheimer’s
In patients with early Alzheimer’s disease, disruptions in brain networks emerge about the same time as chemical markers of the disease appear in the spinal fluid, researchers at Washington University School of Medicine in St. Louis have shown.
While two chemical markers in the spinal fluid are regarded as reliable indicators of early disease, the new study, published in JAMA Neurology, is among the first to show that scans of brain networks may be an equally effective and less invasive way to detect early disease.
“Tracking damage to these brain networks may also help us formulate a more detailed understanding of what happens to the brain before the onset of dementia,” said senior author Beau Ances, MD, PhD, associate professor of neurology and of biomedical engineering.
Diagnosing Alzheimer’s early is a top priority for physicians, many of whom believe that treating patients long before dementia starts greatly improves the chances of success.
Ances and his colleagues studied 207 older but cognitively normal research volunteers at the Charles F. and Joanne Knight Alzheimer’s Disease Research Center at Washington University. Over several years, spinal fluids from the volunteers were sampled multiple times and analyzed for two markers of early Alzheimer’s: changes in amyloid beta, the principal ingredient of Alzheimer’s brain plaques, and in tau protein, a structural component of nerve cells.
The volunteers were also scanned repeatedly using a technique called resting state functional magnetic resonance imaging (fMRI). This scan tracks the rise and fall of blood flow in different brain regions as patients rest in the scanner. Scientists use the resulting data to assess the integrity of the default mode network, a set of connections between different brain regions that becomes active when the mind is at rest.
Earlier studies by Ances and other researchers have shown that Alzheimer’s damages connections in the default mode network and other brain networks.
The new study revealed that this damage became detectable at about the same time that amyloid beta levels began to fall and tau levels started to rise in spinal fluid. The part of the default mode network most harmed by the onset of Alzheimer’s disease was the connection between two brain areas associated with memory, the posterior cingulate and medial temporal regions.
The researchers are continuing to study the connections between brain network damage and the progress of early Alzheimer’s disease in normal volunteers and in patients in the early stages of Alzheimer’s-associated dementia.
(Source: news.wustl.edu)
Copper Identified as Culprit in Alzheimer’s Disease
Copper appears to be one of the main environmental factors that trigger the onset and enhance the progression of Alzheimer’s disease by preventing the clearance and accelerating the accumulation of toxic proteins in the brain. That is the conclusion of a study appearing today in the journal Proceedings of the National Academy of Sciences.
“It is clear that, over time, copper’s cumulative effect is to impair the systems by which amyloid beta is removed from the brain,” said Rashid Deane, Ph.D., a research professor in the University of Rochester Medical Center (URMC) Department of Neurosurgery, member of the Center for Translational Neuromedicine, and the lead author of the study. “This impairment is one of the key factors that cause the protein to accumulate in the brain and form the plaques that are the hallmark of Alzheimer’s disease.”
Copper’s presence in the food supply is ubiquitous. It is found in drinking water carried by copper pipes, nutritional supplements, and in certain foods such as red meats, shellfish, nuts, and many fruits and vegetables. The mineral plays an important and beneficial role in nerve conduction, bone growth, the formation of connective tissue, and hormone secretion.
However, the new study shows that copper can also accumulate in the brain and cause the blood brain barrier – the system that controls what enters and exits the brain – to break down, resulting in the toxic accumulation of the protein amyloid beta, a by-product of cellular activity. Using both mice and human brain cells Deane and his colleagues conducted a series of experiments that have pinpointed the molecular mechanisms by which copper accelerates the pathology of Alzheimer’s disease.
Under normal circumstances, amyloid beta is removed from the brain by a protein called lipoprotein receptor-related protein 1 (LRP1). These proteins – which line the capillaries that supply the brain with blood – bind with the amyloid beta found in the brain tissue and escort them into the blood vessels where they are removed from the brain.
The research team“dosed” normal mice with copper over a three month period. The exposure consisted of trace amounts of the metal in drinking water and was one-tenth of the water quality standards for copper established by the Environmental Protection Agency.
“These are very low levels of copper, equivalent to what people would consume in a normal diet.” said Deane.
The researchers found that the copper made its way into the blood system and accumulated in the vessels that feed blood to the brain, specifically in the cellular “walls” of the capillaries. These cells are a critical part of the brain’s defense system and help regulate the passage of molecules to and from brain tissue. In this instance, the capillary cells prevent the copper from entering the brain. However, over time the metal can accumulate in these cells with toxic effect.
The researchers observed that the copper disrupted the function of LRP1 through a process called oxidation which, in turn, inhibited the removal of amyloid beta from the brain. They observed this phenomenon in both mouse and human brain cells.
The researchers then looked at the impact of copper exposure on mouse models of Alzheimer’s disease. In these mice, the cells that form the blood brain barrier have broken down and become “leaky” – a likely combination of aging and the cumulative effect of toxic assaults – allowing elements such as copper to pass unimpeded into the brain tissue. They observed that the copper stimulated activity in neurons that increased the production of amyloid beta. The copper also interacted with amyloid beta in a manner that caused the proteins to bind together in larger complexes creating logjams of the protein that the brain’s waste disposal system cannot clear.
This one-two punch, inhibiting the clearance and stimulating the production of amyloid beta, provides strong evidence that copper is a key player in Alzheimer’s disease. In addition, the researchers observed that copper provoked inflammation of brain tissue which may further promote the breakdown of the blood brain barrier and the accumulation of Alzheimer’s-related toxins.
However, because metal is essential to so many other functions in the body, the researchers say that these results must be interpreted with caution.
“Copper is an essential metal and it is clear that these effects are due to exposure over a long period of time,” said Deane. “The key will be striking the right balance between too little and too much copper consumption. Right now we cannot say what the right level will be, but diet may ultimately play an important role in regulating this process.”
(Source: urmc.rochester.edu)