Posts tagged brain

ScienceDaily (Aug. 23, 2012) — Scientists at the University of Houston (UH) have discovered what may possibly be a key ingredient in the fight against Parkinson’s disease.

Affecting more than 500,000 people in the U.S., Parkinson’s disease is a degenerative disorder of the central nervous system marked by a loss of certain nerve cells in the brain, causing a lack of dopamine. These dopamine-producing neurons are in a section of the midbrain that regulates body control and movement. In a study recently published in the Proceedings of the National Academy of Sciences (PNAS), researchers from the UH Center for Nuclear Receptors and Cell Signaling (CNRCS) demonstrated that the nuclear receptor liver X receptor beta (LXRbeta) may play a role in the prevention and treatment of this progressive neurodegenerative disease.

"LXRbeta performs an important function in the development of the central nervous system, and our work indicates that the presence of LXRbeta promotes the survival of dopaminergic neurons, which are the main source of dopamine in the central nervous system," said CNRCS director and professor Jan-Åke Gustafsson, whose lab discovered LXRbeta in 1995. "The receptor continues to show promise as a potential therapeutic target for this disease, as well as other neurological disorders."

To better understand the relationship between LXRbeta and Parkinson’s disease, the team worked with a potent neurotoxin, called MPTP, a contaminant found in street drugs that caused Parkinson’s in people who consumed these drugs. In lab settings, MPTP is used in murine models to simulate the disease and to study its pathology and possible treatments.

The researchers found that the absence of LXRbeta increased the harmful effects of MPTP on dopamine-producing neurons. Additionally, they found that using a drug that activates LXRbeta receptors prevented the destructive effects of MPTP and, therefore, may offer protection against the neurodegeneration of the midbrain.

"LXRbeta is not expressed in the dopamine-producing neurons, but instead in the microglia surrounding the neurons," Gustafsson said. "Microglia are the police of the brain, keeping things in order. In Parkinson’s disease the microglia are overactive and begin to destroy the healthy neurons in the neighborhood of those neurons damaged by MPTP. LXRbeta calms down the microglia and prevents collateral damage. Thus, we have discovered a novel therapeutic target for treatment of Parkinson’s disease."

Source: Science Daily

22 August 2012

Scientists have found a switch in the brain which may explain why smoking cannabis causes psychosis and addiction in more than one-in-ten users.

The team, at Aberdeen University found a genetic difference in the switch, probably inherited from early humans who smoked the drug in prehistoric times. The difference may also explain why some people could be more susceptible to conditions such as obesity.

The researchers, at the university’s Kosterlitz Centre for Therapeutics, studied genetic differences around a gene called ‘CNR1’, which produces what are known as cannabinoid receptors in the brain which control parts of the brain involved in memory, mood, appetite and pain.

Cannabinoid receptors activate these areas of the brain when they are triggered by naturally-occurring chemicals in the body known as endocannabinoids. Chemicals found in the cannabis and ‘skunk’ mimic the action of endocannabinoids. It is known that cannabis has pain-relieving and anti-inflammatory properties which can help treat diseases such as multiple sclerosis and arthritis.

However, developing drugs from cannabis to treat these conditions is hampered by the fact that such drugs will have psychoactive side effects - and smoked cannabis can cause addiction and psychosis in up to 12 per cent of users.

Dr Alasdair MacKenzie, who led the research, said:

We looked at one specific genetic difference in CNR1 because we know it is linked to obesity and addiction. What we found was a mutation that caused a change in the genetic switch for the gene itself - a switch that is very ancient and has remained relatively unchanged in over three hundred million years of evolution, since before the time of the dinosaurs.

These genetic ‘switches’ regulate the gene itself, ensuring that it is turned on or off in the right place at the right time and in the right amount. It is normally thought that mutations cause disease by reducing the function of the gene, or the switch that controls it. In this case however, the mutation actually increased the activity of the switch in parts of the brain that control appetite and pain, and also, and most especially, in the part of the brain called the hippocampus, which is affected in psychosis.

He added: We know that this overactive switch is relatively rare in Europeans, but is quite common in African populations. But we were all once African, so something must have decreased it in our early ancestors who left Africa and migrated through Central Asia towards Europe and the north. One possibility we are keen to explore is that once in Central Asia these early migrants came into contact with the cannabis plant, which we know was endemic across that area at that time.

It is possible that the side effects of taking cannabis were such that people with the mutation were not so effective in producing and raising children. Therefore, over the generations the numbers of people with the mutation decreased.

This work is at a very early stage however, and there are likely to be more exciting discoveries - not only on how these differences came about, but also about the role of this genetic switch in health and disease.

Co-researcher Dr Scott Davidson said: Further analysis of this mutation will help us to understand many of the side effects which are associated with cannabis use such as addiction and psychosis.

Professor Ruth Ross, head of the Kosterlitz Centre, an internationally recognised expert in cannabis pharmacology, said: Previously in drug research, attempts to detect the causes of adverse drug reactions have focused on the genes themselves.

Our study is one of the first to explore the possibility that changes in gene switches are involved in causing side effects to drugs. We believe this approach will be crucially important in the future development of more effective personalised medicine, with fewer side effects.

One question that is intriguing the research team is why this overactive genetic switch evolved in the first place.

(Source: Daily Mail)

August 22, 2012

Animals that literally have holes in their brains can go on to behave as normal adults if they’ve had the benefit of a little cognitive training in adolescence. That’s according to new work in the August 23 Neuron, a Cell Press publication, featuring an animal model of schizophrenia, where rats with particular neonatal brain injuries develop schizophrenia-like symptoms.

"The brain can be loaded with all sorts of problems," said André Fenton of New York University. "What this work shows is that experience can overcome those disabilities."

Fenton’s team made the discovery completely by accident. His team was interested in what Fenton considers a core problem in schizophrenia: the inability to sift through confusing or conflicting information and focus on what’s relevant.

"As you walk through the world, you might be focused on a phone conversation, but there are also kids in the park and cars and other distractions," he explained. "These information streams are all competing for our brain to process them. That’s a really challenging situation for someone with schizophrenia."

Fenton and his colleagues developed a laboratory test of cognitive control needed for that kind of focus. In the test, rats had to learn to avoid a foot shock while they were presented with conflicting information. Normal rats can manage that task quickly. Rats with brain lesions can also manage this task, but only up until they become young adults—the equivalent of an 18- or 20-year-old person—when signs of schizophrenia typically set in.

While that was good to see, Fenton says, it wasn’t really all that surprising. But then some unexpected circumstances in the lab led them to test animals with adolescent experience in the cognitive control test again, once they had grown into adults.

These rats should have shown cognitive control deficits, similar to those that had not received prior cognitive training, or so the researchers thought. Instead, they were just fine. Their schizophrenic symptoms had somehow been averted.

Fenton believes their early training for focus forged some critical neural connections, allowing the animals to compensate for the injury still present in their brains in adulthood. Not only were the animals’ behaviors normalized with training, but the patterns of activity in their brains were also.

The finding is consistent with the notion that mental disorders are the consequence of problems in brain development that might have gotten started years before. They raise the optimistic hope that the right kinds of experiences at the right time could change the future by enabling people to better manage their diseases and better function in society. Adolescence, when the brain undergoes significant change and maturation, might be a prime time for such training.

"You may have a damaged brain, but the consequences of that damage might be overcome without changing the damage itself," Fenton says. "You could target schizophrenia, but other disorders aren’t very different," take autism or depression, for example.

And really, in this world of infinite distraction, couldn’t we all use a little more cognitive control?

Source: medicalxpress.com