Scientists have given hope to millions of people worldwide with the discovery of a protein in the brain that can save neurons from dying following traumatic brain injuries. Led by Seong-Seng Tan, the team of scientists from Melbourne’s Howard Florey Institute, Australia found that the production of the protein B5 increases after injuries to the brain. This breakthrough, published in the Journal of Neuroscience, is a crucial step in the formulation of therapeutic strategies.
The increase in the production of B5, known as ‘overexpression’, reduces brain damage because it prevents the neuron from dying. Consequently, it allows neurons to survive in stressed environments, such as after falls, motor vehicle crashes and assaults, which are the leading causes of traumatic brain injuries. Protein B5 is found naturally in the brain and has been identified as a neuroprotective protein, as a result of this study.
The team have tested their hypothesis successfully on mice. Tan states that: “BP5 works by using the cell’s waste disposal system to flush away toxic and damaged proteins produced after injury, which appears to tip the balance towards nerve cell survival, instead of death”.
“Now our challenge is to understand how BP5 performs it neuron-saving function and develop drugs that can do the same thing. Ultimately, we want to deliver the drug to patients suffering brain injury from stroke or trauma to save as many neurons as possible”, Tan said. “Such a drug would limit damage to the brain after the injury, as well as the subsequent few days when injured nerves release ‘suicide factors’ that cause surrounding, healthy neurons to die en masse”.
Tan asserts that this prospective drug would have far reaching prospects including “car accident and assault victims, people undergoing radiotherapy for brain tumours, premature babies that need to be induced, and stroke patients”.
According to the CDC there are almost 1.5 million traumatic brain injuries in the USA alone every year, of which 50,000 people die and a further 235,000 are hospitalized. The long-term outcomes of traumatic brain injuries affect approximately 2% of the US population and not only change people’s thinking and emotions but can also cause epilepsy and increases the risk for brain disorders, such as Alzheimer’s and Parkinson’s disease.
Link confirmed between cocaine abuse and dopamine receptor levels
A team of researchers from the Wake Forest University School of Medicine (NC, USA) have used positron emission tomography (PET) to confirm a link between an individual’s susceptibility to cocaine abuse and dopamine receptor levels in their brain. The team, led by Michael A. Nader, found that the lower the initial number of receptors for the neurotransmitter dopamine, the higher the rate of cocaine use.
Their study, published in Nature Neuroscience, revealed a significant correlation between the number of dopamine receptors, measured before the use of cocaine and the rate at which the drug was later self-administered. The research was conducted using rhesus monkeys, which are regarded as a good substitute model of human drug users. It is hoped that these findings will lead to potential treatment options for cocaine abusers.
The data from the studies present evidence for a predisposition to self-administed cocaine based on the availability of a specific dopamine receptor D2, and demonstrate that the brain dopamine system responds rapidly, following cocaine exposure. The research also showed that starting to use cocaine caused D2 levels to drop significantly and that continuing use of the drug kept D2 levels very low.
This was the first ever study to assess the D2 levels of animals that had never used cocaine and compared them to changes in D2 receptors after the animals had started using the drug. Previous studies have revealed that cocaine abusers had lower levels of D2 in both human and animal subjects compared with nonusers. But it was unclear whether that was a result of cocaine use or if it was a pre-existing trait that predisposed individuals to cocaine abuse.
“The present findings in monkeys suggest that both factors are likely to be true”, Nader commented. “The present findings also suggest that more vulnerable individuals are even more likely to continue using cocaine because of the cocaine-induced reductions in D2 receptor levels”.
Potential treatment options could include increasing D2 receptors ‘pharmacologically’ or improving environmental factors, such as reducing stress.
“Overall, these findings provide unequivocal evidence for a role of D2 receptors in cocaine abuse and suggest that treatments aimed at increasing levels of D2 receptors may have promise for alleviating drug addition”, concluded Nader.
Diabetes drug to help treat Alzheimer’s disease
A drug used to treat patients with diabetes could one day be used to help Alzheimer’s sufferers. David Geldmacher, an associate professor of neurology at the University of Virginia (VA, USA) hopes that the US FDA approved medication for Type 2 diabetes, pioglitazone, will help to reduce Alzheimer’s progression. Research was presented at the 10th International Conference on Alzheimer’s Disease and Related Disorders in Madrid, Spain.
“We believe that the drug may reduce the body’s inflammatory reaction to one of the toxic components that builds up in Alzheimer’s, called amyloid plaque”, said Geldmacher. Preliminary studies have been carried out at the University of Virginia Health System (VA, USA) and Case Western Reserve University (OH, USA).
“We don’t know exactly how pioglitazone works in Alzheimer’s, but there are two possibilities. It could be that the drug reduces the body’s response to the amyloid protein found in Alzheimer’s. Or, it could be that this drug helps brain cells function. The real advantage is that it’s a completely novel approach to treating the disease”.
The team of researchers conducted a study using 25 people with mild-to-moderate Alzheimer’s to establish the safety of long-term use of the drug and found no serious side effects. They also looked at whether pioglitazone treatment might slow progression of the disease.
The study was too small to give conclusive results, but according to Geldmacher: “These preliminary results are promising enough to carry out further studies of pioglitazone in larger groups of patients with Alzheimer’s disease”.
The next step for Geldmacher and his colleagues is to study the effectiveness of pioglitazone in a group of 200–300 Alzheimer’s patients in the USA. “If it works, this treatment might allow people to better hold on to memory and brain function over a period of time, despite having Alzheimer’s”, Geldmacher stated. “It could also complement other treatments and become part of a multi-pronged approach to Alzheimer’s treatment”.
Sleep patterns determine neurodegenerative disease development
A study carried out at the Sleep Unit of Hospital Clínic of Barcelona, Spain has revealed a connection between rapid eye movement (REM) sleep behavior disorders (RBD) and neurodegenerative diseases. The research, led by Alex Iranzo, found that 45% of the assessed patients, who all suffer from RBD, developed neurodegenerative disorders, such as Parkinson’s disease and Lewy body dementia.
These findings have implications for monitoring people with RBD and will allow for the early treatment with neuroprotective drugs to people who are at risk from degenerative diseases. These findings will also be of great interest in the future, when early effective treatment strategies and neuroprotective drugs become available.
Characteristics of RBD, a parasomnia, include unpleasant dreams and uneasiness by screaming, crying, kicking and punching, as well as loss of muscle atonia during REM sleep. To date, it is unclear whether RBD is idiopathic or associated with neurological disease.
The descriptive study, recently published in The Lancet Neurology, assessed 44 patients since 1991. All the patients, most of whom were over 60 years old, had been diagnosed with RBD. It sought to establish the frequency and nature of neurological disorders developing in these patients.
The study suggests that RBD often precedes the development of a neurodegenerative disorder. It revealed that 20 of these patients (45%), after being correctly diagnosed in the center and followed-up during 5 years, developed a neurodegenerative disease. This incidence is much higher than what is expected in the general population of the same age and gender and so scientists concluded that RBD permits the early detection of neurodegenerative diseases, such as Parkinson’s disease, Lewy body dementia, multiple-system atrophy or mild cognitive impairment.
In addition, the 20 patients who developed a neurodegenerative disease were those who had suffered from RBD for the greatest time. This implies that this incidence could be greater in the future.