Posts tagged brain

Scientists at Washington University School of Medicine in St. Louis have taken one of the first detailed looks into how Alzheimer’s disease disrupts coordination among several of the brain’s networks. The results, reported in The Journal of Neuroscience, include some of the earliest assessments of Alzheimer’s effects on networks that are active when the brain is at rest.

“Until now, most research into Alzheimer’s effects on brain networks has either focused on the networks that become active during a mental task, or the default mode network, the primary network that activates when a person is daydreaming or letting the mind wander,” says senior author Beau Ances, MD, assistant professor of neurology. “There are, however, a number of additional networks besides the default mode network that become active when the brain is idling and could tell us important things about Alzheimer’s effects.”

Ances and his colleagues analyzed brain scans of 559 subjects. Some of these subjects were cognitively normal, while others were in the early stages of very mild to mild Alzheimer’s disease. Scientists found that all of the networks they studied eventually became impaired during the initial stages of Alzheimer’s.

“Communications within and between networks are disrupted, but it doesn’t happen all at once,” Ances says. “There’s even one network that has a momentary surge of improved connections before it starts dropping again. That’s the salience network, which helps you determine what in your environment you need to pay attention to.”

Other networks studied by the researchers included:

• the dorsal attention network, which directs attention toward things in the environment that are salient;

• the control network, believed to be active in consciousness and decision-making; and

• the sensory-motor network, which integrates the brain’s control of body movements with sensory feedback (e.g., did the finger that just moved strike the right piano key?).

Scientists also examined Alzheimer’s effects on a brain networking property known as anti-correlations. Researchers identify networks by determining which brain areas frequently become active at the same time, but anti-correlated networks are noteworthy for the way their activities fluctuate: when one network is active, the other network is quiet. This ability to switch back-and-forth between networks is significantly diminished in participants with mild to moderate Alzheimer’s disease.

The default mode network, previously identified as one of the first networks to be impaired by Alzheimer’s, is a partner in two of the three pairs of anti-correlated networks scientist studied.

“While we can’t prove this yet, one hypothesis is that as things go wrong in the processing of information in the default mode network, that mishandled data is passed on to other networks, where it creates additional problems,” Ances says.

It’s not practical to use these network breakdowns to clinically diagnose Alzheimer’s disease, Ances notes, but they may help track the development of the disease and aid efforts to better understand its spread through the brain.

Ances plans to look at other markers for Alzheimer’s disease in the same subjects, such as levels in the cerebrospinal fluid of amyloid beta, a major component of Alzheimer’s plaques.

(Source: news.wustl.edu)

MRI brain scans no longer just show the various regions of brain activity; nowadays the networks in the brain can now be imaged with ever greater precision. This will make functional MRI (fMRI) increasingly powerful in the coming years, leading to tools that can be used in cognitive neuroscience. This is the claim made by Prof. David Norris in his inaugural lecture as Professor of Neuroimaging at the University of Twente on 13 September.

During the twenty years since the invention of fMRI (functional Magnetic Resonance Imaging) developments have come thick and fast, from initially identifying active brain regions to more complex analysis of the connections and hubs in the brain. In his inaugural lecture Norris describes how this has been achieved thanks to not only a growing understanding of the underlying biophysics but also rapid technological developments: scanners with larger magnetic fields, better image-processing techniques and algorithms. His aim is to go beyond merely localizing which parts of the brain are active. The challenge is to answer two questions: How are the various regions interconnected, structurally and functionally? What do the networks in our brains look like?

Faster and more powerful

Back in the 19^th century scientists observed increased blood flow in brain regions that are functionally active. fMRI enables the change in oxygen content to be seen. Haemoglobin, the substance that transports oxygen in the blood, can take the form of oxyhaemoglobin (when it is still combined with oxygen) and deoxyhaemoglobin (when the oxygen has been released), each of which has different magnetic properties. One of the complicating factors when interpreting the scans is that various physiological mechanisms are at work simultaneously, causing the deoxyhaemoglobin level to rise and fall. One of the remedies to increase accuracy, Norris explains, has been to increase the magnetic field strength: there are now MRI scanners operating at 7 Tesla. At the same time the speed at which laminae can be imaged has gone up by leaps and bounds: the entire brain can be scanned in three seconds with a precision of 1 millimetre.

Hubs

The functional connections between parts of the brain can be registered by means of blood flow, but MRI also enables the structural and anatomical connections to be seen. This involves measuring the movement of water molecules caused by the ‘white matter’ in nerve fibres. This technology is known as diffusion-weighted imaging (DWI). Combining these technologies provides a wealth of fresh information on the networks in the brain and the places where many connections come together, the ‘hubs’. Not only have ‘known networks’ thus been proven, so have networks that neuroscience posits as plausible but that have never been measured.

Image showing the distribution of connector hubs on the surface of a flattened brain. The top two figures show the medial views of each hemisphere, the bottom two show the external views.

CMI

The new Centre for Medical Imaging that is to come to the University of Twente campus will soon provide extensive facilities for collaborating in the field of fMRI, says Norris, who is also on the staff of the Donders Institute in Nijmegen.

(Source: utwente.nl)

Researchers from the Centre for Addiction and Mental Health (CAMH) have identified a new role of a chemical involved in controlling the genes underlying memory and learning.

"The brain is a plastic tissue, and we know that learning and memory require various genes to be expressed,” says CAMH Senior Scientist Dr. Art Petronis, who is a senior author on the new study. “Our research has identified how the chemical 5-hmC may be involved in the epigenetic processes allowing this plasticity.” Dr. Petronis is head of the Krembil Family Epigenetics Laboratory in CAMH’s Campbell Family Mental Health Research Institute.

5-hmC is an epigenetic modification of DNA, and was discovered in humans and mice in 2009. DNA modifications are chemical changes to DNA. They flag genes to be turned “on” - signalling the genome to make a protein - or turned “off.” As the overwhelming majority of cells in an individual contain the same genetic code, this pattern of flags is what allows a neuron to use the same genome as a blood or liver cell, but create a completely different and specialized cellular environment.

The research, published online in Nature Structural & Molecular Biology, sheds light on the role of 5-hmC. Intriguingly, it is more abundant in the brain than in other tissues in the body, for reasons not clear to date.

The CAMH team of scientists examined DNA from a variety of tissues, including the mouse and human brain, and looked at where 5-hmC was found in the genome. They detected that 5-hmC had a unique distribution in the brain: it was highly enriched in genes related to the synapse, the dynamic tips of brain cells. Growth and change in the synapse allow different brain cells to “wire” together, which allows learning and memory.

"This enrichment of 5-hmC in synapse-related genes suggests a role for this epigenetic modification in learning and memory," says Dr. Petronis.

The team further showed that 5-hmC had a special distribution even within the gene. The code for one gene can be edited and “spliced” to create several different proteins. Dr. Petronis found that 5-hmC is located at “splice junctions,” the points where the gene is cut before splicing.

"5-hmC may signal the cell’s splicing machinery to generate the diverse proteins that, in turn, give rise to the unprecedented complexity of the brain," he says.

The research team is continuing to investigate the role of 5-hmC in more detail, and to determine whether 5-hmC function is different in people with bipolar disorder and schizophrenia compared to people without these diagnoses.

This research was funded by the U.S National Institutes of Health, the Canadian Institutes of Health Research, and the Tapscott Chair in Schizophrenia Studies at the University of Toronto.

The Centre for Addiction and Mental Health (CAMH) is Canada’s largest mental health and addiction teaching hospital, as well as one of the world’s leading research centres in the area of addiction and mental health. CAMH combines clinical care, research, education, policy development and health promotion to help transform the lives of people affected by mental health and addiction issues.

(Source: Yahoo!)

An enzyme that could represent a powerful new tool for combating Alzheimer’s disease has been discovered by researchers at Mayo Clinic in Florida. The enzyme — known as BACE2 — destroys beta-amyloid, a toxic protein fragment that litters the brains of patients who have the disease. The findings were published online Sept. 17 in the science journal Molecular Neurodegeneration.

Alzheimer’s disease is the most common memory disorder. It affects more that 5.5 million people in the United States. Despite the disorder’s enormous financial and personal toll, effective treatments have not yet been found.

The Mayo research team, led by Malcolm A. Leissring, Ph.D., a neuroscientist at Mayo Clinic in Florida, made the discovery by testing hundreds of enzymes for the ability to lower beta-amyloid levels. BACE2 was found to lower beta-amyloid more effectively than all other enzymes tested. The discovery is interesting because BACE2 is closely related to another enzyme, known as BACE1, involved in producing beta-amyloid.

“Despite their close similarity, the two enzymes have completely opposite effects on beta-amyloid — BACE1 giveth, while BACE2 taketh away,” Dr. Leissring says.

Beta-amyloid is a fragment of a larger protein, known as APP, and is produced by enzymes that cut APP at two places. BACE1 is the enzyme responsible for making the first cut that generates beta-amyloid. The research showed that BACE2 cuts beta-amyloid into smaller pieces, thereby destroying it, instead. Although other enzymes are known to break down beta-amyloid, BACE2 is particularly efficient at this function, the study found.

Previous work had shown that BACE2 can also lower beta-amyloid levels by a second mechanism: by cutting APP at a different spot from BACE1. BACE2 cuts in the middle of the beta-amyloid portion, which prevents beta-amyloid production.

“The fact that BACE2 can lower beta-amyloid by two distinct mechanisms makes this enzyme an especially attractive candidate for gene therapy to treat Alzheimer’s disease,” says first author Samer Abdul-Hay, Ph.D., a neuroscientist at Mayo Clinic in Florida.

The discovery suggests that impairments in BACE2 might increase the risk of Alzheimer’s disease. This is important because certain drugs in clinical use — for example, antiviral drugs used to treat human immunodeficiency virus (HIV) — work by inhibiting enzymes similar to BACE2.

Although BACE2 can lower beta-amyloid by two distinct mechanisms, only the newly discovered mechanism — beta-amyloid destruction — is likely relevant to the disease, the researchers note. This is because the second mechanism, which involves BACE2 cutting APP, does not occur in the brain. The researchers have obtained a grant from the National Institutes of Health to study whether blocking beta-amyloid destruction by BACE2 can increase the risk for Alzheimer’s disease in a mouse model of the disease.

(Source: newswise.com)