Two Dopamine Receptors Are Key to Ritalin Activity
Research reported by scientists from the University of California-San Francisco (UCSF) has shown that, in a rat model, Ritalin (methylphenidate) boosts both the ability to focus on tasks and the speed of learning by increasing the activity of the neurotransmitter dopamine through mechanisms involving two distinct dopamine receptors in the amygdala region of the brain. "We found that a dopamine receptor, known as the D2 receptor, controls the ability to stay focused on a task--the well-known benefit of Ritalin," said Dr. Patricia Janak, co-senior author of the paper. "But we also discovered that another dopamine receptor, D1, underlies learning efficiency." "Since we now know that Ritalin improves behavior through two specific types of neurotransmitter receptors, the finding could help in the development of better targeted drugs, with fewer side effects, to increase focus and learning," said Dr. Antonello Bonci, the other co-senior author of the article. The research assessed the ability of rats to learn that they could get a sugar water reward when they received a signal--a flash of light and a sound. The scientists compared the behavior of animals receiving Ritalin with those that did not receive it, and found those receiving Ritalin learned much better. However, they also found that if they blocked the dopamine D1 receptors with drugs, Ritalin was unable to enhance learning. And if they blocked D2 receptors, Ritalin failed to improve focus. The experiments established the distinct role of each of the dopamine receptors in enabling Ritalin to enhance cognitive performance.
In addition, animals that performed better after Ritalin treatment showed enhanced synaptic plasticity in the amygdala. Enhanced synaptic plasticity is essentially increased efficiency of neural transmission due to strengthening of the communication between neurons where they meet at the synapse. The researchers confirmed this increased plasticity by measuring electrical activity in neurons in the amygdala after Ritalin treatment.
The research also confirmed that learning and focus were enhanced when Ritalin was administered to animals in doses comparable to those used therapeutically in children.
"By identifying the brain mechanisms underlying Ritalin's behavioral enhancements, we can better understand the action of Ritalin, as well as the properties governing brain plasticity," said the paperís lead author, Dr. Kay Tye.
The new research was published online on March 7, 2010 in Nature Neuroscience.
New Form of Prion Disease Described
NIH scientists investigating how prion diseases destroy the brain have observed a new form of the disease in mice that does not cause the hole-filled, sponge-like brain deterioration typically seen in prion diseases. Instead, the disease resembles a form of human Alzheimer's disease, cerebral amyloid angiopathy, that damages brain arteries. The study results, reported by NIH scientists at the National Institute of Allergy and Infectious Diseases (NIAID), are similar to findings from two newly reported human cases of the prion disease Gerstmann-Straussler-Scheinker syndrome (GSS). The mouse findings represent a new mechanism of prion disease brain damage, according to study lead author Dr. Bruce Chesebro, chief of the Laboratory of Persistent Viral Diseases at the NIAIDís Rocky Mountain Laboratories in Montana. The role of a specific cell anchor for prion protein is at the crux of the NIAID study. Normal prion protein uses a specific molecule, glycophosphoinositol (GPI), to fasten to host cells in the brain and other organs. In their study, the NIAID scientists genetically removed the GPI anchor from study mice, preventing the prion protein from fastening to cells and thereby enabling it to diffuse freely in the fluid outside the cells. The scientists then exposed those mice to infectious scrapie and observed the mice for up to 500 days to see if they became sick. The researchers documented signs typical of prion disease including weight loss, lack of grooming, gait abnormalities, and inactivity. But when they examined the brain tissue, they did not observe the sponge-like holes in and around nerve cells typical of prion disease. Instead, the brains contained large accumulations of prion protein plaques trapped outside blood vessels in a disease process known as cerebral amyloid angiopathy, which damages arteries, veins, and capillaries in the brain. In addition, the normal pathway by which fluid drains from the brain appeared to be blocked.
Their study, Dr. Chesebro said, indicates that prion diseases can be divided into two groups--those with plaques that destroy brain blood vessels and those without plaques that lead to the sponge-like damage to nerve cells. Dr. Chesebro said the presence or absence of the prion protein anchor appears to determine which form of disease develops.
The new mouse model used in the study and the two new human GSS cases, which also lack the usual prion protein cell anchor, are the first to show that, in prion diseases, the plaque-associated damage to blood vessels can occur without the sponge-like damage to the brain.
If scientists can find an inhibitor for the new form of prion disease, they might be able to use the same inhibitor to treat similar types of damage in Alzheimer's disease, Dr. Chesebro said.
This new research was published on March 5, 2010 in PLoS Pathogens.
Gut Bacteria Can Cause Obesity
According to a new study, if not regulated properly, the bacteria in our gut responsible for helping in food digestion, could also cause the body to put on weight if they are not properly regulated, a new study has found.
The study published in the journal Science said this occurs when the wrong types of bacteria take over causing low-level inflammation, leading to a pre-diabetic condition and an elevated appetite,
Senior author Andrew Gewirtz of Emory University School of Medicine said in the developed world, it is assumed an increasingly sedentary lifestyle and abundance of low cost, high calorie foods are responsible for the obesity epidemic.
But, the studyís finding suggest excess caloric consumption is not the result of undisciplined eating, rather it is intestinal bacteria contributing to changes in appetite and metabolism.
Gewirtz and fellow researchers studied genetically engineered mice deficient in a key immune system protein i. e. TLR5 that help cells sense bacterial presence, which protein serves in the capacity of the intestinal communityís neighbourhood cop. It knows exactly which bacteria needs keeping in check, and without applying too much force, it also ensures the good bacteria are not harmed.
While, even without TLR5 the immune system can continue bacteria regulation, the job is not done as thoroughly and properly as it should be done. The result is that bacterial composition changes and low level inflammation sets in, desentizing insulin receptors.
Mice deficient in the protein ate 10% more food, ending up 20% heavier than normal mice, including developing metabolic syndrome i.e. a cluster of disorders which in humans increases the risk of heart disease and diabetes.
While, the weight of mice could be regulated by restricting their food intake, they continued to show a decreased sensitivity to insulin.
Gewirtz says this suggests some portion of obesity could be the result of insulin resistance rather than type 2 diabetes and insulin resistance being a consequence of obesity.
The researchers also discovered, when these bacteria were transferred to the intestines of mice not deficient in the protein, but whose intestines had been cleared of all other bacteria, they also developed metabolic syndrome.
However, intestinal bacterial populations acquired at birth are fairly stable in humans, however, diet and anti-biotics can influence them, which other studies indicate is happening as a result of improvements in sanitation and widespread anti-biotic usage.
H1N1 Virus Prevalence Decreasing
Attending a Centre for Disease Control and Prevention meeting last week, William Schaffner, Vanderbilt University Medical Centreís Chair of Preventative Medicine asked virologist Nancy Cox, who is also the Chief of the Influenza Division regarding not seeing an upsurge of traditional influence virus in February and March.
To which, Nancy Cox replied that everyone was surprised, as the least predictable of respiratory illnesses, one cannot predict influenza at all, only keep up.
With an abundance of H1N1 vaccines that no one wants, there is a scarcity of seasonal flu vaccines, indicating the worst of H1N1 may have passed. With each passing day, Schaffner said he becomes more confident the virus is waning, with the worst clearly over.
Often the flu season lasts through March and April, which means getting vaccinated now offers protection for the rest of the season, including preventing the spread of influlenza.
And, with plenty of the H1N1 vaccine available, with many places offering it free of cost, it would also be a good idea to get oneself vaccinated against the H1N1 virus.
Like seasonal flu, H1N1 influenza can make one very sick, including hospitalisation, particularly for those with certain health conditions like asthma, diabetes and heart problems.
Better Diabetes Blood Test
According to a new study, there may be a better method for diabetes screening than the current one which necessitates patients going for hours without eating to take a fasting blood-sugar test.
It seems doctors have found a different kind of blood test, involving measuring long-term sugar control, which is a far superior screening tool for diabetes.
There are 24 million Americans who have diabetes, with a quarter unaware they have the condition.
It is vitally important for at-risk patients to undergo diabetes screening, as if left untreated, diabetes can cause heart disease, nerve damage, and premature death.
However, new research indicates the fasting glucose test, which is the gold standard screening test for diabetes, is not the best option.
Patients refrain from eating anything for a minimum of 8 hours before their blood sugar level are measured. It is less effective than the A1C test, which can be done at any time and which offers a long-term picture of patientsí blood-sugar levels.
Doctors studying 11,000 adult participants found their A1C test results to be related closely to their future odds of heart disease and diabetes, as the highest A1C readings indicated nearly double the risk for heart problems and 16 times the risk for diabetes, but the fasting glucose test had no relation to heart & diabetes risk.
There is convincing evidence researchers of the A1C test being far superior for diagnosing diabetes.
The A1C test measures the personsí blood sugar levels over the past two or three months i. e. it measures the percentage of haemoglobin that is glycated or glycosylated. The American Diabetes Association (ADA) has set the levels for pre-diabetes at 5.7 - 6.4% and 6.5% and higher for a diagnosis of diabetes.