Posts tagged science

May 16, 2012

(Medical Xpress) — When an animal is born, its early experiences help map out the still-forming connections in its brain. As neurons in sensory areas of the brain fire in response to sights, smells, and sounds, synapses begin to form, laying the neuronal groundwork for activity later in life. Not all parts of the brain receive input directly from the external world, however, and researchers have wondered how these regions build their wiring early in development.

The output of this indirect-pathway neuron in the striatum of a mouse brain has been genetically silenced. The neuron has been filled through the attached electrode with a red fluorophore to measure its spine density and the number of active synapses. In the background, other indirect pathway neurons are seen in green and red. Credit: Bernardo Sabatini

New research from Howard Hughes Medical Institute investigator Bernardo Sabatini and colleagues on the basal ganglia, a region of the brain that controls motor planning, indicates that development here follows a different strategy. The new findings suggest that wiring of the basal ganglia during early development is driven not only by experience, but also by a self-reinforcing loop of neuronal signaling. As the loop strengthens, more synapses form.

“What we found is that silencing these neurons doesn’t really change their output patterns — of course they are silenced, but they still find their targets and survive — but instead drastically influences their inputs,” said Bernardo L. Sabatini.

The basal ganglia help an animal select its actions based on sensory and social context, as well as past experience. The new clues about how the basal ganglia gets wired shortly after birth, described in the May 13, 2012, issue of the journal Nature, may help scientists understand what happens when the area goes awry, such as in Parkinson’s disease, when degradation of neurons in the basal ganglia interferes with patients’ ability to initiate appropriate movements, or drug addiction, where overstimulation of the basal ganglia spurs inappropriate actions. Sabatini says his team’s findings also suggest that the process can be easily perturbed during development, and may contribute to human disorders such as cerebral palsy and attention deficit hyperactivity disorder.

Although the basal ganglia do not receive direct messages from the external world, this region of the brain is by no means anatomically isolated: it receives signals from all over the cortex, and its output eventually returns to the cortex. Sabatini, who is at Harvard Medical School, explains that to select a motor action, the brain likely signals through that whole loop. “The question is, how do you lay down the circuits for those patterns?”

The basal ganglia are complex, containing many clusters of cells, some of which send excitatory signals and others inhibitory. Sabatini’s group focused on the basal ganglia’s main input station, the striatum. The striatum uses the information it receives to help direct movement in two ways: a ‘direct’ pathway stimulates motor actions and an ‘indirect’ pathway inhibits them. To learn how striatal activity affects circuit development, Sabatini’s team studied mutant mice whose indirect or direct pathways were turned off (because they were unable to release the inhibitory chemical messenger, GABA).

The group expected that silencing these neurons would prevent them from forming connections with the neurons that should have been receiving their signals. To their surprise, the silenced neurons survived and wired themselves to their targets normally. Unexpectedly, however, silencing the striatum’s direct pathway seemed to prevent formation of the connections sending input to the striatum. Silencing the indirect pathway upped the number of inputs. “We went into this study thinking completely differently,” says Sabatini. “What we found is that silencing these neurons doesn’t really change their output patterns — of course they are silenced, but they still find their targets and survive — but instead drastically influences their inputs.”

To see whether individual cells help set up the basal ganglia circuit, Sabatini’s group turned off a select few striatal neurons, rather than whole pathways, in the mice. They found that silencing these neurons did not affect excitatory connections to the area, suggesting that circuit-level activity patterns set up the basal ganglia’s wiring, rather than individual genes or molecules within cells. “It’s hard to believe that there are molecular cues that specify these structures, because it would be way too complicated,” Sabatini says.

When the group dampened activity in neurons that project from the brain’s cortex to the striatum during development, then examined the brain when the mouse had reached early adulthood (25 days after birth) they saw fewer neuronal connections in the striatum compared to mice that had developed normally suggesting that early perturbations in development can have lasting effects. “That experiments is what told us that it’s the ongoing activity of cortical neurons that is driving this process in the striatum,” Sabatini says. The axons — the slender processes of the neuron that carry electrical impulses — stimulate striatal cells by releasing the excitatory neurotransmitter glutamate, telling them to make more synapses and stabilize them, he adds.

Sabatini believes that the basal ganglia tests random connection patterns after an animal is born and reinforces the correct ones. This type of plasticity of the basal ganglia probably lasts into adulthood, because animals are constantly learning to take new actions. Using genetically engineered mice that allow researchers to control exactly which neurons to inactivate and when, Sabatini’s group is now studying how perturbations affect the wiring later in life.

Sabatini expects that these results will get us a step closer to understanding human disease. “Maybe we will show that there’s hope for therapy,” he adds. “If it is plastic, maybe we can recover.”

Provided by Howard Hughes Medical Institute

Source: medicalxpress.com

May 16, 2012

(Medical Xpress) — Scientists at the University of Bristol have shed new light on one of the great unanswered questions of neuroscience: how the brain initiates rhythmic movements like walking, running and swimming.

The Xenopus frog tadpole is a small, simple vertebrate

While experiments in the 1970s using electrical brain stimulation identified areas of the brain responsible for starting locomotion, the precise neuron-by-neuron pathway has not been described in any vertebrate – until now. 

To find this pathway, Dr. Edgar Buhl and colleagues in Bristol’s School of Biological Sciences studied a small, simple vertebrate: the Xenopus frog tadpole.

They found that the pathway to initiate swimming consists of just four types of neurons.  By touching skin on the head of the tadpole and applying cellular neurophysiology and anatomy techniques, the scientists identified nerve cells that detect the touch on the skin, two types of brain nerve cells which pass on the signal, and the motor nerve cells that control the swimming muscles. 

Dr. Buhl said: “These findings address the longstanding question of how locomotion is initiated following sensory stimulation and, for the first time in any vertebrate, define in detail a direct pathway responsible.  They could thus be of great evolutionary interest and could also open the path to understanding initiation of locomotion in other vertebrates.”

When mechanisms in the brain that initiate locomotion break down – for example, in people with Parkinson’s disease – starting to walk becomes a real problem.  Therefore, understanding the initiation of swimming in tadpoles could be a first step towards understanding the initiation of locomotion in more complex vertebrates, including people, and may eventually have implications for treating movement disorders such as Parkinson’s.

The research is published today in the Journal of Physiology.

Provided by University of Bristol

Source: medicalxpress.com

May 15th, 2012

Technique could help those with C6, C7 spinal cord injuries.

Surgeons at Washington University School of Medicine in St. Louis have restored some hand function in a quadriplegic patient with a spinal cord injury at the C7 vertebra, the lowest bone in the neck. Instead of operating on the spine itself, the surgeons rerouted working nerves in the upper arms. These nerves still “talk” to the brain because they attach to the spine above the injury.

Following the surgery, performed at Barnes-Jewish Hospital, and one year of intensive physical therapy, the patient regained some hand function, specifically the ability to bend the thumb and index finger. He can now feed himself bite-size pieces of food and write with assistance.

The case study, published online May 15 in the Journal of Neurosurgery, is, to the authors’ knowledge, the first reported case of using nerve transfer to restore the ability to flex the thumb and index finger after a spinal cord injury.

“This procedure is unusual for treating quadriplegia because we do not attempt to go back into the spinal cord where the injury is,” says surgeon Ida K. Fox, MD, assistant professor of plastic and reconstructive surgery at Washington University, who treats patients at Barnes-Jewish Hospital. “Instead, we go out to where we know things work — in this case the elbow — so that we can borrow nerves there and reroute them to give hand function.”

To detour around the block in this patient’s C7 spinal cord injury and return hand function, Mackinnon operated in the upper arms. There, the working nerves that connect above the injury (green) and the non-working nerves that connect below the injury (red) run parallel to each other, making it possible to tap into a functional nerve and direct those signals to a non-functional neighbor (yellow arrow). Image adapted from Eric Young image available in press release mentioned.

Although patients with spinal cord injuries at the C6 and C7 vertebra have no hand function, they do have shoulder, elbow and some wrist function because the associated nerves attach to the spinal cord above the injury and connect to the brain. Since the surgeon must tap into these working nerves, the technique will not benefit patients who have lost all arm function due to higher injuries — in vertebrae C1 through C5.

The surgery was developed and performed by the study’s senior author Susan E. Mackinnon, MD, chief of the Division of Plastic and Reconstructive Surgery at Washington University School of Medicine. Specializing in injuries to peripheral nerves, she has pioneered similar surgeries to return function to injured arms and legs.

Mackinnon originally developed this procedure for patients with arm injuries specifically damaging the nerves that provide the ability to flex the thumb and index finger. This is the first time she has applied this peripheral nerve technique to return limb function after a spinal cord injury.

[Video: Surgeons restore some hand function to quadriplegic patient]
Surgeons at Washington University School of Medicine in St. Louis have restored some hand function in a quadriplegic patient with a spinal cord injury at the C7 vertebra, the lowest bone in the neck. Instead of operating on the spine itself, the surgeons rerouted working nerves in the upper arms. These nerves still “talk” to the brain because they attach to the spine above the injury. Following the surgery, performed at Barnes-Jewish Hospital, and one year of intensive physical therapy, the patient regained the ability to pinch and can now feed himself bite-size pieces of food and write with assistance.

“Many times these patients say they would like to be able to do very simple things,” Fox says. “They say they would like to be able to feed themselves or write without assistance. If we can restore the ability to pinch, between thumb and index finger, it can return some very basic independence.”

Mackinnon cautions that the hand function restored to the patient was not instantaneous and required intensive physical therapy. It takes time to retrain the brain to understand that nerves that used to bend the elbow now provide pinch, she says.

Though this study reports only one case, Mackinnon and her colleagues do not anticipate a limited window of time during which a patient with a similar spinal cord injury must be treated with this nerve transfer technique. This patient underwent the surgery almost two years after his injury. As long as the nerve remains connected to the support and nourishment of the spinal cord, even though it no longer “talks” to the brain, the nerve and its associated muscle remain healthy, even years after the injury.

“The spinal cord is the control center for the nerves, which run like spaghetti all the way out to the tips of the fingers and the tips of the toes,” says Mackinnon, the Sydney M. Shoenberg Jr. and Robert H. Shoenberg Professor and director of the School of Medicine’s Center for Nerve Injury and Paralysis. “Even nerves below the injury remain healthy because they are still connected to the spinal cord. The problem is that these nerves no longer ‘talk’ to the brain because the spinal cord injury blocks the signals.”

To detour around the block in this patient’s C7 spinal cord injury and return hand function below the level of the injury, Mackinnon operated in the upper arms. There, the working nerves that connect above the injury and the non-working nerves that connect below the injury run parallel to each other, making it possible to tap into a functional nerve and direct those signals to a non-functional neighbor.

In this case, Mackinnon took a non-working nerve that controls the ability to pinch and plugged it into a working nerve that drives one of two muscles that flex the elbow. After the surgery, the bicep still flexes the elbow, but a second muscle, called the brachialis, that used to also provide elbow flexion, now bends the thumb and index finger.

“This is not a particularly expensive or overly complex surgery,” Mackinnon says. “It’s not a hand or a face transplant, for example. It’s something we would like other surgeons around the country to do.”

By Julia Evangelou Strait

Source: Neuroscience News

ScienceDaily (May 15, 2012) — Attention, college students cramming between midterms and finals: Binging on soda and sweets for as little as six weeks may make you stupid.

New research suggests that binging on soda and sweets for as little as six weeks may make you stupid. (Credit: © RTimages / Fotolia)

A new UCLA rat study is the first to show how a diet steadily high in fructose slows the brain, hampering memory and learning — and how omega-3 fatty acids can counteract the disruption. The peer-reviewed Journal of Physiology publishes the findings in its May 15 edition.

"Our findings illustrate that what you eat affects how you think," said Fernando Gomez-Pinilla, a professor of neurosurgery at the David Geffen School of Medicine at UCLA and a professor of integrative biology and physiology in the UCLA College of Letters and Science. "Eating a high-fructose diet over the long term alters your brain’s ability to learn and remember information. But adding omega-3 fatty acids to your meals can help minimize the damage."

While earlier research has revealed how fructose harms the body through its role in diabetes, obesity and fatty liver, this study is the first to uncover how the sweetener influences the brain.

The UCLA team zeroed in on high-fructose corn syrup, an inexpensive liquid six times sweeter than cane sugar, that is commonly added to processed foods, including soft drinks, condiments, applesauce and baby food. The average American consumes more than 40 pounds of high-fructose corn syrup per year, according to the U.S. Department of Agriculture. “We’re not talking about naturally occurring fructose in fruits, which also contain important antioxidants,” explained Gomez-Pinilla, who is also a member of UCLA’s Brain Research Institute and Brain Injury Research Center. “We’re concerned about high-fructose corn syrup that is added to manufactured food products as a sweetener and preservative.”

Gomez-Pinilla and study co-author Rahul Agrawal, a UCLA visiting postdoctoral fellow from India, studied two groups of rats that each consumed a fructose solution as drinking water for six weeks. The second group also received omega-3 fatty acids in the form of flaxseed oil and docosahexaenoic acid (DHA), which protects against damage to the synapses — the chemical connections between brain cells that enable memory and learning.

"DHA is essential for synaptic function — brain cells’ ability to transmit signals to one another," Gomez-Pinilla said. "This is the mechanism that makes learning and memory possible. Our bodies can’t produce enough DHA, so it must be supplemented through our diet."

The animals were fed standard rat chow and trained on a maze twice daily for five days before starting the experimental diet. The UCLA team tested how well the rats were able to navigate the maze, which contained numerous holes but only one exit. The scientists placed visual landmarks in the maze to help the rats learn and remember the way.

Six weeks later, the researchers tested the rats’ ability to recall the route and escape the maze. What they saw surprised them.

"The second group of rats navigated the maze much faster than the rats that did not receive omega-3 fatty acids," Gomez-Pinilla said. "The DHA-deprived animals were slower, and their brains showed a decline in synaptic activity. Their brain cells had trouble signaling each other, disrupting the rats’ ability to think clearly and recall the route they’d learned six weeks earlier."

The DHA-deprived rats also developed signs of resistance to insulin, a hormone that controls blood sugar and regulates synaptic function in the brain. A closer look at the rats’ brain tissue suggested that insulin had lost much of its power to influence the brain cells.

"Because insulin can penetrate the blood-brain barrier, the hormone may signal neurons to trigger reactions that disrupt learning and cause memory loss," Gomez-Pinilla said.

He suspects that fructose is the culprit behind the DHA-deficient rats’ brain dysfunction. Eating too much fructose could block insulin’s ability to regulate how cells use and store sugar for the energy required for processing thoughts and emotions.

"Insulin is important in the body for controlling blood sugar, but it may play a different role in the brain, where insulin appears to disturb memory and learning," he said. "Our study shows that a high-fructose diet harms the brain as well as the body. This is something new."

Gomez-Pinilla, a native of Chile and an exercise enthusiast who practices what he preaches, advises people to keep fructose intake to a minimum and swap sugary desserts for fresh berries and Greek yogurt, which he keeps within arm’s reach in a small refrigerator in his office. An occasional bar of dark chocolate that hasn’t been processed with a lot of extra sweetener is fine too, he said.

Still planning to throw caution to the wind and indulge in a hot-fudge sundae? Then also eat foods rich in omega-3 fatty acids, like salmon, walnuts and flaxseeds, or take a daily DHA capsule. Gomez-Pinilla recommends one gram of DHA per day.

"Our findings suggest that consuming DHA regularly protects the brain against fructose’s harmful effects," said Gomez-Pinilla. "It’s like saving money in the bank. You want to build a reserve for your brain to tap when it requires extra fuel to fight off future diseases."

Source: Science Daily

ScienceDaily (May 15, 2012) — Child abuse or neglect are strong predictors of major health and emotional problems, but little is known about how the chronicity of the maltreatment may increase future harm apart from other risk factors in a child’s life.

This chart illustrates the individual childhood and adult outcomes according to the number of reports that occurred before the event of interest. Because it was possible for some children to enter the study period with a pre-existing condition, these are indicated as gray or black bars with the legend indicating the outcome occurred “before the study.” Chronicity is associated with increasing risk for all but child maltreatment perpetration, violent delinquency, and head or brain injury. In these cases, there is a slight decline in prevalence for the highest category compared with middle categories, but in all cases having reports was associated with higher rates of outcomes. (Credit: Image courtesy of Washington University in St. Louis)

In a new study published in the current issue of the journal Pediatrics, Melissa Jonson-Reid, PhD, child welfare expert and a professor at the Brown School at Washington University in St. Louis, looked at how chronic maltreatment impacted the future health and behavior of children and adults.

The study tracked children by number of child maltreatment reports (zero to four or more) and followed the children into early adulthood, by which time some of the children had become parents.

The study sought to determine how well the number of child maltreatment reports predicted poor outcomes in adolescence, such as delinquency, substance abuse in the teen years or getting a sexually transmitted disease.

"For every measure studied, a more chronic history of child maltreatment reports was powerfully predictive of worse outcomes," Jonson-Reid says.

"For most outcomes, having a single maltreatment report put children at a 20 percent to 50 percent higher risk than non-maltreated comparison children.

In addition, a series of adult outcomes were tracked to see if the chronicity of maltreatment still mattered after controlling for the poor outcomes in adolescence. Adult outcomes included adult substance abuse or growing up and having children whom they then maltreated.

"In models of adult outcomes, children with four or more reports were about least twice as likely to later abuse their own children and have contact with the mental health system, even when controlling for the negative outcomes during adolescence." Jonson-Reid says that there appears to be good reason to put resources into preventing ongoing maltreatment.

"Successfully interrupting chronic child maltreatment may well reduce risk of a wide range of other costly child and adolescent health and behavioral problems," she says.

Jonson-Reid cites a recently published Centers for Disease Control and Prevention study estimating lifetime costs for a single year’s worth of children reported for maltreatment at $242 billion.

"What our study illustrates is that these costs are even more likely to accrue for children who continue to be re-reported," she says.

The study also found that maltreatment predicts a range of negative adolescent outcomes, and those adolescent outcomes then predict poor adult outcomes.

"If the poor outcomes in adolescence can be dealt with effectively, then later adult outcomes may also be forestalled," Jonson-Reid says.

"Our findings could therefore be interpreted as supporting many current evidence-based interventions that seek to improve behavioral and social functioning among children and adolescents who have experienced trauma like abuse or neglect."

Source: Science Daily

ScienceDaily (May 15, 2012) — A novel mechanism for anxiety behaviors, including a previously unrecognized inhibitory brain signal, may inspire new strategies for treating psychiatric disorders, University of Chicago researchers report.

By testing the controversial role of a gene called Glo1 in anxiety, scientists uncovered a new inhibitory factor in the brain: the metabolic by-product methylglyoxal. The system offers a tantalizing new target for drugs designed to treat conditions such as anxiety disorder, epilepsy, and sleep disorders.

The study, published in the Journal of Clinical Investigation, found that animals with multiple copies of the Glo1 gene were more likely to exhibit anxiety-like behavior in laboratory tests. Further experiments showed that Glo1 increased anxiety-like behavior by lowering levels of methylglyoxal (MG). Conversely, inhibiting Glo1 or raising MG levels reduced anxiety behaviors.

"Animals transgenic for Glo1 had different levels of anxiety-like behavior, and more copies made them more anxious," said Abraham Palmer, PhD, assistant professor of human genetics at the University of Chicago Medicine and senior author of the study. "We showed that Glo1 was causally related to anxiety-like behavior, rather than merely correlated."

In 2005, a comparison of different mouse strains found a link between anxiety-like behaviors and Glo1, the gene encoding the metabolic enzyme glyoxylase 1. However, subsequent studies questioned the link, and the lack of an obvious connection between glyoxylase 1 and brain function or behavior made some scientists skeptical.

Read more …

May 15, 2012

A drug made from the saliva of the Gila monster lizard is effective in reducing the craving for food. Researchers at the Sahlgrenska Academy, University of Gothenburg, have tested the drug on rats, who after treatment ceased their cravings for both food and chocolate.

In a study with rats published in the Journal of Neuroscience, Assistant Professor Karolina Skibicka and her colleagues show that exendin-4 effectively reduces the cravings for food. Credit: Photo: University of Gothenburg

An increasing number of patients suffering from type 2 diabetes are offered a pharmaceutical preparation called Exenatide, which helps them to control their blood sugar. The drug is a synthetic version of a natural substance called exendin-4, which is obtained from a rather unusual source – the saliva of the Gila monster lizard (Heloderma suspectum), North America’s largest lizard.

Researchers at the Sahlgrenska Academy at the University of Gothenburg, have now found an entirely new and unexpected effect of the lizard substance.

In a study with rats published in the Journal of Neuroscience, Assistant Professor Karolina Skibicka and her colleagues show that exendin-4 effectively reduces the cravings for food.

"This is both unknown and quite unexpected effect," comments an enthusiastic Karolina Skibicka:

" Our decision to eat is linked to the same mechanisms in the brain which control addictive behaviours. We have shown that exendin-4 affects the reward and motivation regions of the brain"

The implications of the findings are significant” states Suzanne Dickson, Professor of Physiology at the Sahlgrenska Academy: “Most dieting fails because we are obsessed with the desire to eat, especially tempting foods like sweets. As exendin-4 suppresses the cravings for food, it can help obese people to take control of their weight,” suggests Professor Dickson.

Research on exendin-4 also gives hope for new ways to treat diseases related to eating disorders, for example, compulsive overeating.

Another hypothesis for the Gothenburg researchers’ continuing studies is that exendin-4 may be used to reduce the craving for alcohol.

"It is the same brain regions which are involved in food cravings and alcohol cravings, so it would be very interesting to test whether exendin-4 also reduces the cravings for alcohol,” suggests Assistant Professor Skibicka.

Provided by University of Gothenburg

Source: medicalxpress.com

May 15, 2012

(Medical Xpress) — New research from Uppsala University, Sweden, suggests that an active lifestyle in late life protects grey matter and cognitive functions in humans. The findings are now published in the scientific journal Neurobiology of Aging.

In a new study, a multidisciplinary research team from the Uppsala University has systematically studied 331 men and women at the age of 75 years. The researchers examined whether an active lifestyle is tied to brain health in seniors living in Uppsala, Sweden. The brain structure of each participant was measured using magnetic imaging technology, so-called MRT, and various memory tests were administered in order to monitor the seniors’ cognitive status.

“We found that those elderly who reported to be more active in daily routine had larger grey and white matter and showed better performances on various memory tests, compared to those who had a sedentary lifestyle. Interestingly, active elderly had also more grey matter in the precuneus, a brain region that typically shrinks at the beginning of Alzheimer’s disease. Our findings suggest that an active lifestyle is a promising strategy for counteracting cognitive aging late in life,” says Christian Benedict.

The data for the study were taken from the major epidemiological study Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). http://www.medsci.uu.se/pivus/

More information: Benedict C et al., Association between physical activity and brain health in older adults, Neurobiology of Aging, in press. http://www.sciencedirect.com/science/article/pii/S0197458012002618

Provided by Uppsala University

Source: medicalxpress.com

ScienceDaily (May 14, 2012) — A new study consisting of inducing cells to express telomerase, the enzyme which — metaphorically — slows down the biological clock — was successful. The research provides a “proof-of-principle” that this “feasible and safe” approach can effectively “improve health span.”

Pictured are Maria A. Blasco and Bruno M. Bernardes de Jesús (co-author) in the CNIO building in Madrid. (Credit: CNIO)

A number of studies have shown that it is possible to lengthen the average life of individuals of many species, including mammals, by acting on specific genes. To date, however, this has meant altering the animals’ genes permanently from the embryonic stage — an approach impracticable in humans. Researchers at the Spanish National Cancer Research Centre (CNIO), led by its director María Blasco, have demonstrated that the mouse lifespan can be extended by the application in adult life of a single treatment acting directly on the animal’s genes. And they have done so using gene therapy, a strategy never before employed to combat aging. The therapy has been found to be safe and effective in mice.

The results were recently published in the journal EMBO Molecular Medicine. The CNIO team, in collaboration with Eduard Ayuso and Fátima Bosch of the Centre of Animal Biotechnology and Gene Therapy at the Universitat Autònoma de Barcelona (UAB), treated adult (one-­‐year-­‐old) and aged (two-­‐year-­‐old) mice, with the gene therapy delivering a “rejuvenating” effect in both cases, according to the authors.

Mice treated at the age of one lived longer by 24% on average, and those treated at the age of two, by 13%. The therapy, furthermore, produced an appreciable improvement in the animals’ health, delaying the onset of age-­‐related diseases — like osteoporosis and insulin resistance — and achieving improved readings on aging indicators like neuromuscular coordination.

The gene therapy consisted of treating the animals with a DNA-­modified virus, the viral genes having been replaced by those of the telomerase enzyme, with a key role in aging. Telomerase repairs the extreme ends or tips of chromosomes, known as telomeres, and in doing so slows the cell’s and therefore the body’s biological clock. When the animal is infected, the virus acts as a vehicle depositing the telomerase gene in the cells.

This study “shows that it is possible to develop a telomerase-­based anti-­aging gene therapy without increasing the incidence of cancer,” the authors affirm. “Aged organisms accumulate damage in their DNA due to telomere shortening, [this study] finds that a gene therapy based on telomerase production can repair or delay this kind of damage,” they add.

'Resetting' the biological clock

Telomeres are the caps that protect the end of chromosomes, but they cannot do so indefinitely: each time the cell divides the telomeres get shorter, until they are so short that they lose all functionality. The cell, as a result, stops dividing and ages or dies. Telomerase gets around this by preventing telomeres from shortening or even rebuilding them. What it does, in essence, is stop or reset the cell’s biological clock.

But in most cells the telomerase gene is only active before birth; the cells of an adult organism, with few exceptions, have no telomerase. The exceptions in question are adult stem cells and cancer cells, which divide limitlessly and are therefore immortal — in fact several studies have shown that telomerase expression is the key to the immortality of tumour cells.

It is precisely this risk of promoting tumour development that has set back the investigation of telomerase-­‐based anti-­‐aging therapies.

In 2007, Blasco’s group demonstrated that it was feasible to prolong the lives of transgenic mice, whose genome had been permanently altered at the embryonic stage, by causing their cells to express telomerase and, also, extra copies of cancer-­‐resistant genes. These animals live 40% longer than is normal and do not develop cancer.

The mice subjected to the gene therapy now under test are likewise free of cancer. Researchers believe this is because the therapy begins when the animals are adult so do not have time to accumulate sufficient number of aberrant divisions for tumours to appear.

Also important is the kind of virus employed to carry the telomerase gene to the cells. The authors selected demonstrably safe viruses that have been successfully used in gene therapy treatment of hemophilia and eye disease. Specifically, they are non-­‐replicating viruses derived from others that are non-­‐pathogenic in humans.

This study is viewed primarily as “a proof-­‐of-­‐principle that telomerase gene therapy is a feasible and generally safe approach to improve healthspan and treat disorders associated with short telomeres,” state Virginia Boccardi (Second University of Naples) and Utz Herbig (New Jersey Medical School-­‐University Hospital Cancer Centre) in a commentary published in the same journal.

Although this therapy may not find application as an anti-­‐aging treatment in humans, in the short term at least, it could open up a new treatment option for ailments linked with the presence in tissue of abnormally short telomeres, as in some cases of human pulmonary fibrosis.

More healthy years

As Blasco says, “aging is not currently regarded as a disease, but researchers tend increasingly to view it as the common origin of conditions like insulin resistance or cardiovascular disease, whose incidence rises with age. In treating cell aging, we could prevent these diseases.”

With regard to the therapy under testing, Bosch explains: “Because the vector we use expresses the target gene (telomerase) over a long period, we were able to apply a single treatment. This might be the only practical solution for an anti-­‐aging therapy, since other strategies would require the drug to be administered over the patient’s lifetime, multiplying the risk of adverse effects.”

Source: Science Daily

May 14th, 2012

Controlled trial shows improved spasticity, reduced pain after smoking medical marijuana.

A clinical study of 30 adult patients with multiple sclerosis (MS) at the University of California, San Diego School of Medicine has shown that smoked cannabis may be an effective treatment for spasticity – a common and disabling symptom of this neurological disease.

The placebo-controlled trial also resulted in reduced perception of pain, although participants also reported short-term, adverse cognitive effects and increased fatigue. The study will be published in the Canadian Medical Association Journal on May 14.

Principal investigator Jody Corey-Bloom, MD, PhD, professor of neurosciences and director of the Multiple Sclerosis Center at UC San Diego, and colleagues randomly assigned participants to either the intervention group (which smoked cannabis once daily for three days) or the control group (which smoked identical placebo cigarettes, also once a day for three days). After an 11-day interval, the participants crossed over to the other group.

“We found that smoked cannabis was superior to placebo in reducing symptoms and pain in patients with treatment-resistant spasticity, or excessive muscle contractions,” said Corey-Bloom.

Earlier reports suggested that the active compounds of medical marijuana were potentially effective in treating neurologic conditions, but most studies focused on orally administered cannabinoids. There were also anecdotal reports of MS patients that endorsed smoking marijuana to relieve symptoms of spasticity.

However, this trial used a more objective measurement, a modified Ashford scale which graded the intensity of muscle tone by measuring such things as resistance in range of motion and rigidity. The secondary outcome, pain, was measured using a visual analogue scale. The researchers also looked at physical performance (using a timed walk) and cognitive function and – at the end of each visit – asked patients to assess their feeling of “highness.”

Although generally well tolerated, smoking cannabis did have mild effects on attention and concentration. The researchers noted that larger, long-terms studies are needed to confirm their findings and determine whether lower doses can result in beneficial effects with less cognitive impact.

The current study is the fifth clinical test of the possible efficacy of cannabis for clinical use reported by the University of California Center for Medicinal Cannabis Research (CMCR). Four other human studies on control of neuropathic pain also reported positive results.

Source: Neuroscience News