Excessive alcohol when you’re young could have lasting impacts on your brain

Alcohol misuse in young people causes significant changes in their brain function and structure. This and other findings were recently reviewed by Dr Daniel Hermens from the University of Sydney’s Brain and Mind Research Institute in the journal Cortex.

"Young people are particularly vulnerable to the damaging effects of alcohol misuse," said Dr Hermens.

Most people have their first alcoholic drink during adolescence and while they drink less frequently than adults, they tend to drink more on each occasion - binge drinking.

The early functional signs of brain damage from alcohol misuse are visual, learning, memory and executive function impairments. These functions are controlled by the hippocampus and frontal structures of the brain, which are not fully mature until around 25 years of age.

Structural signs of alcohol misuse include shrinking of the brain and significant changes to white matter.

In his review, Dr Hermens notes that changes in a young person’s brain caused by alcohol misuse could either represent a predisposition (genetic or environmental) to alcohol misuse, or a marker for future risk of ongoing misuse. Whichever it is, there is no doubt that the more frequent the alcohol misuse, the greater the damage and the less likely the brain is to recover from that damage.

"When the toxicity of alcohol stops your brain from laying down new memories, you experience a blackout," said Dr Hermens. Young people who binge drink may only drink once a week, but on a massive night out they may have three to four blackouts, which begins to cause serious damage to their brain.

One of the best predictors of a person having problems with alcohol is their earliest age of first use. But changing the legal drinking age is not the answer. In Australia the legal drinking age is 18, three years earlier than in the US. Despite the difference in legal drinking age, the age of first use is the same between the two countries.

Another key factor affecting young people who drink is mental health, “poor mental health more than doubles a young person’s risk of alcohol and other substance misuse” says Dr Hermens.

The solution lies in education, treatment and prevention. Dr Hermens and his team have been working with NSW Health to prepare a set of guidelines for health carers to identify and respond to early stages of brain impairment in young people resulting from alcohol misuse. They are currently working on a set of educational charts that inform young people of the risks of irresponsible drinking.

It may be possible to use cognitive remediation to change the drinking habits of young drinkers and prevent relapse. At the same time, vitamin supplements or other medicines may effectively treat some of the structural changes, and it may be possible to develop protective agents that can prevent young brains from the damaging effects of alcohol.

"More work needs to be done in this area. Excessive alcohol use accounts for 4 percent of the global burden of disease. We would save a lot of money and improve the quality of life for millions of people if we could prevent the mental and physical problems associated with alcohol misuse" said Dr Hermens.

Silent stroke can cause Parkinson’s disease

Scientists at The University of Manchester have for the first time identified why a patient who appears outwardly healthy may develop Parkinson’s disease.

Whilst conditions such as a severe stroke have been linked to the disease, for many sufferers the tremors and other symptoms of Parkinson’s disease can appear to come out of the blue. Researchers at the university’s Faculty of Life Sciences have now discovered that a small stroke, also known as a silent stroke, can cause Parkinson’s disease. Their findings have been published in the journal “Brain Behaviour and Immunity”.

Unlike a severe stroke, a silent stroke can show no outward symptoms of having taken place. It happens when a blood vessel in the brain is blocked for only a very short amount of time and often a patient won’t know they have suffered from one. However, it now appears one of the lasting effects of a silent stroke can be the death of dopaminergic neurons in the substantia nigra in the brain, which is an important region for movement coordination.

Dr. Emmanuel Pinteaux led the research: “At the moment we don’t know why dopaminergic neurons start to die in the brain and therefore why people get Parkinson’s disease. There have been suggestions that oxidative stress and aging are responsible. What we wanted to do in our study was to look at what happens in the brain away from the immediate area where a silent stroke has occurred and whether that could lead to damage that might result in Parkinson’s disease.”

The team induced a mild stroke similar to a silent stroke in the striatum area of the brain in mice. They found there was inflammation and brain damage in the striatum following the stroke, which they had expected. What the researchers didn’t expect was the impact on another area of the brain, the substantia nigra. When they analysed the substantia nigra they recorded a rapid loss of Substance P (a key chemical involved in its functions) as well as inflammation.

The team then analysed changes in the brain six days after the mild stroke and found neurodegeneration in the substantia nigra. Dopaminergic neurones had been killed.

Talking about the findings Dr Pinteaux said: “It is well known that inflammation following a stroke can be very damaging to the brain. But what we didn’t fully appreciate was the impact on areas of the brain away from the location of the stroke. Our work identifying that a silent stroke can lead to Parkinson’s disease shows it is more important than ever to ensure stroke patients have swift access to anti-inflammatory medication. These drugs could potentially either delay or stop the on-set of Parkinson’s disease.”

Dr Pinteaux continued: “What our findings also point to is the importance of maintaining a healthy lifestyle. There are already guidelines about exercise and healthy eating to help reduce the risk of having a stroke and our research suggests that a healthy lifestyle can be applied to Parkinson’s disease as well.”

Following the publication of these findings, Dr Pinteaux hopes to set up a clinical investigation on people who have had a silent stroke to assess dopaminergic neuron degeneration. In the meantime he will be working closely will colleagues at The University of Manchester to better understand the mechanisms of inflammation in the substantia nigra. 

Even the Smallest Possible Stroke Can Damage Brain Tissue and Impair Cognitive Function

Blocking a single tiny blood vessel in the brain can harm neural tissue and even alter behavior, a new study from the University of California, San Diego has shown. But these consequences can be mitigated by a drug already in use, suggesting treatment that could slow the progress of dementia associated with cumulative damage to miniscule blood vessels that feed brain cells. The team reports their results in the December 16 advance online edition of Nature Neuroscience.

"The brain is incredibly dense with vasculature. It was surprising that blocking one small vessel could have a discernable impact on the behavior of a rat," said Andy Y. Shih, lead author of the paper who completed this work as a postdoctoral fellow in physics at UC San Diego. Shih is now an assistant professor at the Medical University of South Carolina.

Working with rats, Shih and colleagues used laser light to clot blood at precise points within small blood vessels that dive from the surface of the brain to penetrate neural tissue. When they looked at the brains up to a week later, they saw tiny holes reminiscent of the widespread damage often seen when the brains of patients with dementia are examined as a part of an autopsy.

These micro-lesions are too small to be detected with conventional MRI scans, which have a resolution of about a millimeter. Nearly two dozen of these small vessels enter the brain from a square millimeter area of the surface of the brain.

"It’s controversial whether that sort of damage has consequences, although the tide of evidence has been growing as human diagnostics improve," said David Kleinfeld, professor of physics and neurobiology, who leads the research group.

To see whether such minute damage could change behavior, the scientists trained thirsty rats to leap from one platform to another in the dark to get water.

The rats readily jump if they can reach the second platform with a paw or their snout, or stretch farther to touch it with their whiskers. Many rats can be trained to rely on a single whisker if the others are clipped, but if they can’t feel the far platform, they won’t budge.

"The whiskers line up in rows and each one is linked to a specific spot in the brain," Shih said. "By training them to use just one whisker, we were able to distill a behavior down to a very small part of the brain."

When Shih blocked single microvessels feeding a column of brain cells that respond to signals from the remaining whisker, the rats still crossed to the far platform when the gap was small. But when it widened beyond the reach of their snouts, they quit.

The FDA-approved drug memantine, prescribed to slow one aspect of memory decline associated with Alzheimer’s disease, ameliorated these effects. Rats that received the drug jumped whisker-wide gaps, and their brains showed fewer signs of damage.

"This data shows us, for the first time, that even a tiny stroke can lead to disability," said Patrick D. Lyden, a co-author of the study and chair of the department of neurology at Cedars-Sinai Medical Center in Los Angeles. "I am afraid that tiny strokes in our patients contribute—over the long term—to illness such as dementia and Alzheimer’s disease," he said, adding that "better tools will be required to tell whether human patients suffer memory effects from the smallest strokes."

“We used powerful tools from biological physics, many developed in Kleinfeld’s laboratory at UC San Diego, to link stroke to dementia on the unprecedented small scale of single vessels and cells,” Shih said. “At my new position at MUSC, I plan to work on ways to improve the detection of micro-lesions in human patients with MRI. This way clinicians may be able to diagnose and treat dementia earlier.”

Study Shows Working Memory Is Driven By Prefrontal Cortex And Dopamine

One of the unique features of the human mind is its ability re-prioritize its goals and priorities as situations change and new information arises. This happens when you cancel a planned cruise because you need the money to repair your broke-down car, or when you interrupt your morning jog because your cell phone is ringing in your pocket.

In a new study published in the Proceedings of the National Academy of Sciences (PNAS), researchers from Princeton University say that they have discovered the mechanisms that control how our brains use new information to modify our existing priorities.

The team of researchers at Princeton’s Neuroscience Institute (PNI) used functional magnetic resonance imaging (fMRI) to scan subjects and find out where and how the human brain reprioritizes goals. Unsurprisingly, they found that the shifting of goals takes place in the prefrontal cortex, a region of the brain which is known to be associated with a variety of higher-level behaviors. They also observed that the powerful neurotransmitter dopamine – also known as the “pleasure chemical” – appears to play a critical role in this process.

Using a harmless magnetic pulse, the scientists interrupted activity in the prefrontal cortex of the participants while they were playing games and found they were unable to switch to a different task in the game.

“We have found a fundamental mechanism that contributes to the brain’s ability to concentrate on one task and then flexibly switch to another task,” explained Jonathan Cohen, co-director of PNI and the university’s Robert Bendheim and Lynn Bendheim Thoman Professor in Neuroscience.

“Impairments in this system are central to many critical disorders of cognitive function such as those observed in schizophrenia and obsessive-compulsive disorder.”

Previous research had already demonstrated that when the brain uses new information to modify its goals or behaviors, this information is temporarily filed away into the brain’s working memory, a type of short-term memory storage. Until now, however, scientists have not understood the mechanisms controlling how this information is updated.

Hypertension traced to source in brain

When the heart works too hard, the brain may be to blame, says new Cornell research that is changing how scientists look at high blood pressure (hypertension). The study, published in the Journal of Clinical Investigation in November, traces hypertension to a newfound cellular source in the brain and shows that treatments targeting this area can reverse the disease.

In what peer reviewers are calling “a new paradigm” for tackling the worldwide hypertension epidemic, this insight into its roots could give hope to the billion people it currently afflicts. Hypertension occurs when the force of blood against vessel walls grows strong enough to potentially cause such problems as heart attack, stroke and heart or kidney disease. The heart pumps harder, and often the hormone angiotensin-II (AngII) gets the pressure cooking by triggering nerve cells that constrict blood vessels.

"We knew the central nervous system orchestrates this process, and now we’ve found the conductor," said Robin Davisson, the Andrew Dickson White Professor of Molecular Physiology with a joint appointment at Cornell’s College of Veterinary Medicine and Weill Cornell Medical College.

Two-thirds of Americans have hypertension, which is the leading cause of North America’s No. 1 killer: heart disease, according to the Centers for Disease Control and Prevention.

Davisson’s lab traced neurochemical signals back to endoplasmic reticulum (ER), the protein factory and stress-management control center in every cell. If something goes wrong in a cell, the ER activates processes to adapt to the stress. Long-term ER stress can cause chronic disease, and several stressors that ER responds to have been connected to hypertension. Davisson’s lab found that high levels of AngII put stress on the ER, which responds by triggering the cascade of neural and hormonal signals that start hypertension.

But not just any cell’s ER can conduct this complex orchestra. Those that can trigger the signal cascade are clustered near the bottom of the brain in a gatelike structure called the subfornical organ (SFO). Unlike most of the brain, the SFO hangs outside a protective barrier that keeps most circulating particles from entering the brain. The SFO can interact with particles like AngII that are too big to cross through and can also communicate with the brain’s inner chambers.

This is good news for developing therapies—because the SFO sits outside the barrier, it can be reached through such normal treatment routes as pills or injections rather than riskier brain procedures. Davisson’s lab showed that treatments that inhibit ER stress in the SFO can completely stop AngII-based hypertension and lower blood pressure to normal levels.

"Our work provides the first evidence that higher levels of AngII cause ER stress in the SFO, that this causes hypertension, and that we can do something about it," said Davisson. "This finding may also suggest a role for ER stress in hypertension types that don’t involve AngII, like some spontaneous or genetic forms."

Inspired by the paradigm shift that this study has sparked, the editors of the Journal of Clinical Investigation published a commentary concluding that this discovery “opens new avenues for investigation and may lead to new therapeutic approaches for this disease.”

Brain imaging identifies bipolar risk

Researchers from the Black Dog Institute and University of NSW have used brain imaging technology to show that young people with a known genetic risk of bipolar but no clinical signs of the condition have clear and quantifiable differences in brain activity when compared to controls.

“We found that the young people who had a parent or sibling with bipolar disorder had reduced brain responses to emotive faces, particularly a fearful face. This is an extremely promising breakthrough,” says study leader Professor Philip Mitchell.

Affecting around 1 in 75 Australians, bipolar disorder involves extreme and often unpredictable fluctuations in mood. The mood swings and associated behaviours such as disinhibited behaviour, aggression and severe depression, have a significant impact on day-to-day life, careers and relationships. Bipolar has the highest suicide rate of all psychiatric disorders.

“We know that bipolar is primarily a biological illness with a strong genetic influence but triggers are yet to be understood. Being able to identify young people at risk will enable implementation of early intervention programs, giving them the best chance for a long and happy life,” says Prof Mitchell.

Researchers used functional MRI to visualise brain activity when participants were shown pictures of happy, fearful or calm (neutral) human faces. Results showed that those with a genetic risk of bipolar displayed significantly reduced brain activity in a specific part of the brain known to regulate emotional responses.

“Our results show that bipolar disorder may be linked to a dysfunction in emotional regulation and this is something we will continue to explore,” Professor Mitchell said.

“And we now have an extremely promising method of identifying children and young people at risk of bipolar disorder.”

 “We expect that early identification will significantly improve outcomes for people that go on to develop bipolar disorder, and possibly even prevent onset in some people.”

Results are published this week in Biological Psychiatry and come from the NHMRC-funded ‘Kids and Sibs study’, the biggest research study in the world focusing on genetic and environmental aspects of bipolar disorder. Based at the Black Dog Institute, the trial is still recruiting.

Aerobic exercise boosts brain power in elderly

Evidence for the importance of physical activity in keeping and potentially improving cognitive function throughout life was found in a literature review in Psychonomic Bulletin & Review by Hayley Guiney and Liana Machado from the University of Otago, New Zealand.

• Cognitive functions such as task switching, selective attention, and working memory appear to benefit from aerobic exercise. Studies in older adults reviewed by the authors consistently found that fitter individuals scored better in mental tests than their unfit peers.
  
  
• Scores in mental tests improved in participants who were assigned to an aerobic exercise regimen compared to those assigned to stretch and tone classes.
  
  
• Exercise has been found to positively affect mental tasks relating to activities such as driving, an activity where age is often seen as a limiting factor.
  
  
• MRI studies of aging have shown that, as compared with unfit, highly fit older adults exhibit less age-related atrophy in the prefrontal and temporal cortices; preserved neural tracts connecting the prefrontal cortex to other regions of the brain; superior white matter integrity in the corpus callosum; greater gray matter density in the frontal, temporal, and parietal cortices; and greater hippocampal volumes.
  
  
• Physically active older adults have both higher circulating neurotrophin levels and gray matter volumes in the prefrontal and cingulate cortex.
  
  
• These results were not replicated in children or young adults, except for memory tasks. Both the updating of working memory and the volume of information which could be held was also better in young fitter individuals or those put on an aerobic exercise regime. “Although the evidence to date supports a wider range of executive functions benefiting from regular exercise in older adults, the relative lack of supportive evidence in young adults and children may, in part, reflect a poverty of studies, especially controlled trials, in these age groups,” the authors suggest.

Rice opens new window on Parkinson’s disease

Rice University scientists have discovered a new way to look inside living cells and see the insoluble fibrillar deposits associated with Parkinson’s disease.

The combined talents of two Rice laboratories – one that studies the misfolded proteins that cause neurodegenerative diseases and another that specializes in photoluminescent probes – led to the spectroscopic technique that could become a valuable tool for scientists and pharmaceutical companies.

The research by the Rice labs of Angel Martí and Laura Segatori appeared online today in the Journal of the American Chemical Society.

The researchers designed a molecular probe based on the metallic element ruthenium. Testing inside live neuroglioma cells, they found the probe binds with the misfolded alpha-synuclein proteins that clump together and form fibrils and disrupt the cell’s functions. The ruthenium complex lit up when triggered by a laser – but only when attached to the fibril, which allowed aggregation to be tracked using photoluminescence spectroscopy.