Posts tagged brain

ScienceDaily (Aug. 16, 2012) — Researchers have found what they believe is the key to understanding why the human brain is larger and more complex than that of other animals.

The human brain, with its unequaled cognitive capacity, evolved rapidly and dramatically.

"We wanted to know why," says James Sikela, PhD, who headed the international research team that included researchers from the University of Colorado School of Medicine, Baylor College of Medicine and the National Institutes of Mental Health. "The size and cognitive capacity of the human brain sets us apart. But how did that happen?"

"This research indicates that what drove the evolutionary expansion of the human brain may well be a specific unit within a protein — called a protein domain — that is far more numerous in humans than other species."

The protein domain at issue is DUF1220. Humans have more than 270 copies of DUF1220 encoded in the genome, far more than other species. The closer a species is to humans, the more copies of DUF1220 show up. Chimpanzees have the next highest number, 125. Gorillas have 99, marmosets 30 and mice just one. “The one over-riding theme that we saw repeatedly was that the more copies of DUF1220 in the genome, the bigger the brain. And this held true whether we looked at different species or within the human population.”

Sikela, a professor at the CU medical school, and his team also linked DUF1220 to brain disorders. They associated lower numbers of DUF1220 with microcephaly, when the brain is too small; larger numbers of the protein domain were associated with macrocephaly, when the brain is too large.

The findings were reported today in the online edition of The American Journal of Human Genetics. The researchers drew their conclusions by comparing genome sequences from humans and other animals as well as by looking at the DNA of individuals with microcephaly and macrocephaly and of people from a non-disease population.

"The take home message was that brain size may be to a large degree a matter of protein domain dosage," Sikela says. "This discovery opens many new doors. It provides new tools to diagnose diseases related to brain size. And more broadly, it points to a new way to study the human brain and its dramatic increase in size and ability over what, in evolutionary terms, is a short amount of time."

Source: Science Daily

ScienceDaily (Aug. 16, 2012) — In multiple sclerosis, the immune system attacks nerves in the brain and spinal cord, causing movement problems, muscle weakness and loss of vision. Immune cells called dendritic cells, which were previously thought to contribute to the onset and development of multiple sclerosis, actually protect against the disease in a mouse model, according to a study published by Cell Press in the August issue of the journal Immunity. These new insights change our fundamental understanding of the origins of multiple sclerosis and could lead to the development of more effective treatments for the disease.

"By transfusing dendritic cells into the blood, it may be possible to reduce autoimmunity," says senior study author Ari Waisman of University Medical Center of Johannes Gutenberg University Mainz. "Beyond multiple sclerosis, I can easily imagine that this approach could be applied to other autoimmune diseases, such as inflammatory bowel disease and psoriasis."

In an animal model of multiple sclerosis known as experimental autoimmune encephalomyelitis (EAE), immune cells called T cells trigger the disease after being activated by other immune cells called antigen-presenting cells (APCs). Dendritic cells are APCs capable of activating T cells, but it was not known whether dendritic cells are the APCs that induce EAE.

In the new study, Waisman and his team used genetic methods to deplete dendritic cells in mice. Unexpectedly, these mice were still susceptible to EAE and developed worse autoimmune responses and disease clinical scores, suggesting that dendritic cells are not required to induce EAE and other APCs stimulate T cells to trigger the disease. The researchers also found that dendritic cells reduce the responsiveness of T cells and lower susceptibility to EAE by increasing the expression of PD-1 receptors on T cells.

"Removing dendritic cells tips the balance toward T cell-mediated autoimmunity," says study author Nir Yogev of University Medical Center of Johannes Gutenberg University Mainz. "Our findings suggest that dendritic cells keep immunity under check, so transferring dendritic cells to patients with multiple sclerosis could cure defects in T cells and serve as an effective intervention for the disease."

Source: Science Daily

By: Richard C. Lewis | 2012.08.16

Everyone knows the adage: “If something sounds too good to be true, then it probably is.” So, why, then, do some people fall for scams and why are older folks especially prone to being duped?

An answer, it seems, is because a specific area of the brain has deteriorated or is damaged, according to researchers at the University of Iowa. By examining patients with various forms of brain damage, the researchers report they’ve pinpointed the precise location in the human brain, called the ventromedial prefrontal cortex, that controls belief and doubt, and which explains why some of us are more gullible than others.

Patients with damage to the ventromedial prefrontal cortex were roughly twice as likely to believe a given ad, even when given disclaimer information pointing out it was misleading. And, they were more likely to buy the item, regardless of whether misleading information had been corrected. Photo by Bill Adams.

“The current study provides the first direct evidence beyond anecdotal reports that damage to the vmPFC (ventromedial prefrontal cortex) increases credulity. Indeed, this specific deficit may explain why highly intelligent vmPFC patients can fall victim to seemingly obvious fraud schemes,” the researchers wrote in the paper published in a special issue of the journal Frontiers in Neuroscience.

Read more …

16 August 2012

Ten out of 11 patients with severe Tourette’s Syndrome have reported improvement after receiving deep brain stimulation surgery, according to University of New South Wales research published in the American Journal of Psychiatry. 

Tourette’s Syndrome is a neurological disorder characterised by repetitive involuntary movements and vocalisations called tics and can also include behavioural difficulties. 

Deep brain stimulation is a therapeutic technique that involves placing electrodes at specific sites in the brain to deliver continuous stimulation from an implanted generator.

Study leader, UNSW Scientia Professor Perminder Sachdev, says deep brain stimulation may have an important role in treating Tourette’s Syndrome in its most severe form. He says tics are generally treated with medications that work well in about 50 to 70 per cent of cases. Drugs, however, can have side effects in some patients. 

Eleven patients, eight of them in their late thirties with severe Tourette’s Syndrome, underwent deep brain stimulation at St Andrew’s Hospital in Brisbane - under the care of neurologist Professor Peter Silburn and neurosurgeon Associate Professor Terry Coyne - as part of the study. They were followed up initially one month after surgery and then around a year after the procedure.

Ten out of the 11 patients involved in the joint UNSW Medicine and Asia-Pacific Centre for Neuromodulation study reported immediate improvement in tic severity soon after the treatment, with an overall 48 per cent reduction in monitor tics and a 57 per cent reduction in phonic tics at final follow-up. Associated psychiatric symptoms also improved.

“Because deep brain stimulation involves brain surgery, it has some risks, even though these are low. It is therefore only likely to be used in individuals who are significantly affected by their tics,” Scientia Professor Sachdev says.

“Our study demonstrates that when suitably selected, patients can benefit greatly from deep brain stimulation.”

Source: University of New South Wales

The vast majority of people with addiction have suffered significant previous trauma, and many people who struggle with addiction suffer from post-traumatic stress disorder (PTSD) simultaneously. But the treatment of these patients has posed a conundrum: experts have believed that PTSD treatment should not begin until the addicted person achieves lasting abstinence, because of the risk that PTSD treatment may trigger relapse, yet addicted people with untreated PTSD are rarely able to abstain for long.

Now, a new study suggests that there may be no need to wait. Researchers found that using exposure therapy — the gold-standard treatment for PTSD, which involves exposure to memories and reminders of patients’ past trauma — can successfully reduce symptoms of PTSD, even when people with addiction continue to use drugs. And, although exposure therapy requires patients to face some of their worst fears, it does not increase their drug use or prompt them to drop out of treatment more than ordinary addiction therapy, the study found.

“The exciting thing in my view is that [the study] supports people with drug and alcohol problems having access to other forms of psychological interventions, rather than being fobbed off and told to sort out their alcohol or drug problem first,” says Michael Farrell, director of the National Drug and Alcohol Research Center at the University of New South Wales in Sydney, Australia, where the research was conducted.

The finding could potentially help the majority of those who suffer from addiction or PTSD: one-half to two-thirds of people with addictions suffer from PTSD concurrently, or have in the past, and about the same proportion of people with PTSD also have substance use disorders.

The new study involved 103 people with both conditions. Most were addicted to multiple drugs, primarily heroin, marijuana and alcohol. More than two-thirds of the participants had been traumatized during childhood, with almost half reporting a history of sexual abuse.

Researchers randomly assigned half of the participants to simply continue the addiction treatment of their choice, whether it was detoxification leading to abstinence, residential treatment or maintenance on medications like methadone and buprenorphine (Suboxone, Subutex).

The other half received their usual treatment, plus exposure therapy for PTSD, which consisted of 13 one-on-one sessions with a clinical psychologist, meeting about once a week for 90 minutes at a time. The therapy began with education about PTSD and addiction, including instruction on cognitive techniques to address distressing thoughts that could lead to relapse. Then, when patients were ready, they were exposed to reminders of their traumatic experience, which they usually avoided out of fear of triggering flashbacks and intense anxiety. Exposure therapy works to reduce or eliminate these PTSD symptoms by breaking patients’ cycle of fear and avoidance.

Indeed, participants in the exposure treatment “demonstrated significantly greater reductions in PTSD symptom severity compared with participants randomized to receive usual treatment alone,” the authors wrote. However, drug use in the exposure therapy group didn’t decline any more than it did in the usual treatment group. Both groups saw a reduction in the severity of addiction but in each case, the majority of participants continued to use drugs. Notably, however, drug use did not increase due to exposure therapy.

“These findings challenge the widely held view that patients need to be abstinent before any trauma work, let alone prolonged exposure therapy, is commenced,” the authors wrote. “[F]indings from the present study demonstrate that abstinence is not required.”

Importantly, however, while the findings showed that carefully delivered exposure therapy can help, they did not support the practice of forcing addicts to confront trauma in settings where they do not feel safe or in control. Exposure therapy is calibrated so that patients do not become overwhelmed or feel helpless; in contrast, coercion by the therapist can re-traumatize patients and worsen both PTSD and addiction symptoms, previous studies have shown.

In other words, it’s not clear that treating people with addiction by compelling them to recall or re-enact traumatic experiences — a commonly used tactic in group settings — actually helps. What the current study shows is that when trained clinical psychologists carefully deliver exposure therapy in a tightly monitored trial, they can help ease PTSD symptoms in people with addiction.

By Maia Szalavitz | August 15, 2012

Source: TIME

In 2000, a team of neuroscientists put an unusual idea to the test. Stress and depression, they knew, made neurons wither and die – particularly in the hippocampus, a brain area crucial for memory. So the researchers put some stressed-out rats on an antidepressant regimen, hoping the mood boost might protect some of those hippocampal neurons. When they checked in a few weeks later, though, the team found that rats’ hippocampuses hadn’t just survived intact; they’d grown whole new neurons – bundles of them. But that’s only the beginning of our tale.

Neural stem cells (green) in the hippocampus huddle around a neuron (purple), listening for stray signals.

By the time 2009 rolled around, another team of researchers was suggesting that human brains might get a similar hippocampal boost from antidepressants. The press announced the discovery with headlines like, “Antidepressants Grow New Brain Cells” – although not everyone agreed with that conclusion. Still, whether the principle applied to humans or not, a far more basic question was begging to be answered: How, exactly, does a brain tell new cells to form?

“Well, through synapses, of course,” you might answer – and that’d be a very reasonable guess. After all, synapses are how most neurons talk to each other: electrochemical information is “squirted” from a tiny tendril of one neuron into the tip of a tendril on another; and cells throughout most of the brain share essentially this same mechanism for passing signals along: The signals coming out of Neuron A’s synapses keep bugging Neuron B by stimulating its synapses, until finally Neuron B caves under peer pressure and bugs Neuron C with the signal… and so on.

There are, however, two significant exceptions to this system.

The first exception was discovered a few years ago, as scientists got more and more curious about the role of neuroglia (also known as just “glia”), synapse-less cells that many had assumed were just there to serve as structural support for neurons. A 2008 study showed that glia help control cerebral blood flow, and research in 2010 demonstrated that some glia – cells known as astrocytes – actively listen for and respond to certain neurotransmitter messages. These so-called “quiet cells” are actually pretty loud talkers once you learn to tune in to their chatter.

The second exception to the synapse rule is even more mysterious – in large part because it’s a brand-new discovery: As the journal Nature reports, a team led by Hongjun Song at the Johns Hopkins University School of Medicine have found that neural stem cells “listen in” on the stray chemical signals that leak from synapses.

You can imagine neural stem cells as being sort of “neural embryos” – depending on the surrounding conditions, they can develop into neurons or into glia. And here’s what’s strange about the way these cells communicate: They respond not to any single synaptic signal, but to the overall chemical “vibe” of their environment – to chronic feelings of stress, for instance. By way of response, they may morph into neurons or glia – or even tell the brain to crank out some all-new cells.

Neural stem cells seem to be particularly interested in the chemical GABA (gamma-aminobutyric acid) – a neurotransmitter that’s known to be involved in inhibiting signals from other neurons. When scientists artificially block these stem cells’ GABA receptors from receiving messages, the cells “wake up” and start replicating – but when those GABA signals are allowed to reach the receptors, the stem cells stay dormant.

“In this case,” Song explains, “GABA communication keeps the brain stem cells in reserve, so if we don’t need them, we don’t use them up.”

In short, leaky synapses aren’t wasteful – as a matter of fact, they’re essential to the brain’s self-sculpting abilities. And this implies something pretty interesting: It isn’t just individual signals that convey neural information, but whole experiences. In that respect, a brain – whether it belongs to a rat or a human – is unlike any computer on earth.

By Ben Thomas | August 15, 2012

Source: Scientific American

When something goes wrong in your brain, you’d think it would be a good idea to get rid of the problem. Turns out, sometimes it’s best to keep hold of it. By preventing faulty proteins from being destroyed, researchers have delayed the symptoms of a degenerative brain disorder.

SNAP25 is one of three proteins that together make up a complex called SNARE, which plays a vital role in allowing neurons to communicate with each other. In order to work properly, all the proteins must be folded in a specific way. CSP alpha is one of the key proteins that ensures SNAP25 is correctly folded.

Cells have a backup system to deal with any misfolded proteins – they are destroyed by a bell-shaped enzyme called a proteasome, which pulls the proteins inside itself and breaks them down.

People with a genetic mutation that affects the CSP alpha protein – and its ability to correctly fold SNAP25 – can develop a rare brain disorder called neuronal ceroid lipofuscinosis (NCL). The disorder causes significant damage to neurons – people affected gradually lose their cognitive abilities and struggle to move normally.

To find out what role proteasomes might play in NCL, Manu Sharma and his colleagues at Stanford University in California blocked the enzyme in mice that were bred to lack CSP alpha. “We weren’t sure what would happen,” says Sharma. Either the misfolded SNAP25 would accumulate and harm the cells, or some of the misfolded proteins may work well enough to retain some of their function.

Longer life

It appears it was the latter. Mice bred to lack CSP alpha suffer the same physical and cognitive problems as humans, and tend to survive for about 65 to 80 days, rather than the normal 670 days. But mice injected with a drug that blocked protease lived, on average, an extra 15 days. “Fifteen days might not sound like much, but as a percentage it’s quite significant,” says Sharma. What’s more, treated mice were able to stave off measurable movement and cognitive symptoms for an extra 10 days.

The finding goes against the idea that neurodegenerative disorders should be treated by clearing away misfolded proteins, rather than trying to rescue their function. “People normally think that protease isn’t working hard enough,” says Nico Dantuma at the Karolinska Institute in Stockholm, Sweden, who was not involved in the study.

But whether or not the drugs are likely to work in other neurodegenerative disorders involving aggregations of misfolded proteins, such as Alzheimer’s and Parkinson’s disease, is up for debate. “I don’t think their results prove that clearing misfolded proteins is not a useful therapeutic,” says Ana Maria Cuervo at Albert Einstein College of Medicine in New York. Other studies that increase the degrading of misfolded proteins have been shown to improve symptoms in other neurodegenerative diseases, she says.

"There are two sides of the coin," says Dantuma. "You might rescue functioning proteins from being degraded… but it’s too early to extrapolate these results to Alzheimer’s and Parkinson’s disease."

In the meantime, drugs that block proteasome are already used to treat cancer, so Sharma hopes they can soon be trialled in people with NCL.

Source: NewScientist