First Indication Of People Naturally Protected Against Rabies Found In Remote Amazonian Communities

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Main Category: Tropical Diseases
Also Included In: Infectious Diseases / Bacteria / Viruses
Article Date: 03 Aug 2012 - 0:00 PDT Current ratings for:
First Indication Of People Naturally Protected Against Rabies Found In Remote Amazonian Communities

Challenging conventional wisdom that rabies infections are 100 percent fatal unless immediately treated, scientists studying remote populations in the Peruvian Amazon at risk of rabies from vampire bats found 11 percent of those tested showed protection against the disease, with only one person reporting a prior rabies vaccination. Ten percent appear to have survived exposure to the virus without any medical intervention. The findings from investigators at the U.S. Centers for Disease Control and Prevention (CDC) were published in the August 2012 issue of the American Journal of Tropical Medicine and Hygiene.

"The overwhelming majority of rabies exposures that proceed to infections are fatal. However, our results open the door to the idea that there may be some type of natural resistance or enhanced immune response in certain communities regularly exposed to the disease," said Amy Gilbert with the CDC's National Center for Emerging and Zoonotic Infectious Diseases, who is the paper's lead author. "This means there may be ways to develop effective treatments that can save lives in areas where rabies remains a persistent cause of death."

Rabies experts estimate the disease kills 55,000 people each year in Africa and Asia alone, and appears to be on the rise in China, the former Soviet Republics, southern Africa, and Central and South America. According to the CDC, in the United States, human deaths from rabies have declined over the past century from 100 annually to an average of two per year thanks to an aggressive campaign to vaccinate domestic animals against the disease.

In general, people who believe they may have been exposed to rabies are advised to immediately seek treatment which involves post-exposure prophylaxis (PEP) - a series of injections - to prevent the exposure from causing an active infection. These preventive treatments, when administered promptly, are 100 percent successful at preventing disease. Scientists have documented only a small number of individual cases, including one last year in California, in which an exposure to rabies proceeded to infection and the victim survived. Most of those survivors still required intensive medical attention, including one case in Wisconsin in which doctors induced a coma, though this approach has not been successful in most subsequent cases.

This CDC study was conducted in collaboration with the Peruvian Ministry of Health as part of a larger project to understand better bat-human interactions and its relation to rabies and emerging diseases that may be transmitted by bats. For their research, scientists traveled to two communities (Truenococha and Santa Marta) in a remote section of the Peruvian Amazon where outbreaks of fatal infections with rabies caused by bites from vampire bats - the most common "natural reservoir" for the disease in Latin America - have occurred regularly over the last two decades. They interviewed 92 people, 50 of whom reported previous bat bites. Blood samples were taken from 63 individuals and seven (11 percent) were found to have "rabies virus neutralizing antibodies."

One out of the seven individuals reported receiving a rabies vaccination - which generates antibodies to the rabies virus?"but there was no evidence that the other six had received anti-rabies vaccine prior to the blood sampling or had sought out any medical attention for a bat bite, evidence that they had harbored the virus itself.

The researchers acknowledged that they could not conclusively determine whether the antibodies were caused by an exposure to the virus that was somehow insufficient to produce disease. But they believe their evidence "suggests that (rabies virus) exposure is not invariably fatal to humans."

Gilbert said non-fatal exposures may happen more often than some think because "unless people have clinical symptoms of the disease they may not go to the hospital or clinic, particularly where access is limited."

"We all still agree that nearly everyone who is found to be experiencing clinical symptoms of rabies dies," Gilbert said. "But we may be missing cases from isolated high-risk areas where people are exposed to rabies virus and, for whatever reason, they don't develop disease."

In the Amazon region where the study was conducted - the Province Datem del Maranon in the Loreto Department of northern Peru - vampire bats, which live off of mammalian blood, regularly come out at night and prefer to feed on livestock. But in the absence of those food sources, they are known to seek out a meal from humans. They can use their extremely sharp teeth and the anticoagulant that naturally occurs in their saliva (appropriately referred to as "draculin") to feed on a sleeping person without awakening them. The rabies virus circulates extensively among vampire bat colonies in the region, and when an infected bat feeds, it passes along the virus to its host.

"This type of thorough and persistent scientific rabies investigation lends continued support to the belief that even the most dangerous of infectious diseases may be amenable to treatment," said James W. Kazura, MD noted infectious disease expert and president of the American Society of Tropical Medicine and Hygiene (ASTMH). "Continued investment of resources is essential for us to protect the health and well-being of innocent people whose lives and livelihoods are needlessly threatened by infectious diseases like rabies."

Gilbert and her colleagues hope their findings will prompt further studies in remote, at-risk communities to see if the results are replicated. In an editorial accompanying the study, Rodney E. Willoughby, a pediatric disease specialist at Children's Hospital of Wisconsin, said if it turns out there are distinct populations of people with "complete or relative resistance to rabies," there could be the potential to use whole genome sequencing to help develop new, life-saving treatments for rabies infections.

"Careful, respectful genetic study of these genetically unique populations may provide information on which pathways in human biochemistry and physiology promote resistance to human rabies," he wrote. "Equally important, knowing that there is a continuum of disease, even for infectious diseases like rabies, should push us harder to try for cures when confronted by so-called untreatable infectious diseases...."

Gilbert noted that the study was done as part of a larger public health effort to address a series of rabies outbreaks in the Amazon, where some health officials are now considering conducting pre-emptive vaccination campaigns in areas where risk of rabies is high and availability of medical care low. She said that while her study highlights people who appear to have survived an exposure to the virus, the fact remains that rabies outbreaks in small communities in the region have left tragic results.

"These are very small villages and, when they witness ten people dying from what is a horrible disease, it is incredibly traumatic," Gilbert said. "We want to help raise awareness of the problem and try to develop a more proactive response."

Article adapted by Medical News Today from original press release. Source: Burness Communications
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Shift Workers And Older People Experience Social Exclusion

Main Category: Psychology / Psychiatry
Also Included In: Seniors / Aging;  Public Health
Article Date: 15 Dec 2011 - 0:00 PST

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Older people and those who work non-standard hours are less likely to feel integrated into society, according to a study funded by the Economic and Social Research Council (ESRC).

"Feeling part of society usually involves participating in certain activities such as sports, the arts, volunteering or social networking," says Dr Matt Barnes who led the research. "Our research shows that older people and those who work unusual hours face particular barriers to participating in such activities."

The study points out that the Government promotes work as the best route to personal well-being, with worklessness going hand in hand with low income and social exclusion. Yet, Dr Barnes' research shows that working uncommon hours can also have implications for people's opportunities to engage and feel integrated in society.

Two-thirds of workers work at unusual times. Although shops and other facilities are beginning to adapt, such workers still find their leisure time constrained by the limited availability of services, as well as other people with whom to spend their free time.

Compared with people who work a standard week (Monday to Friday, between 8am and 7pm), these workers spend less time on face-to-face social and relational activities, particularly if they work in the evening or at the weekend. On average, evening workers spend six hours 43 minutes on participatory activities per week and Sunday workers just over five hours, compared with over eight hours for those who work normal hours.

"By getting people to keep a diary and analysing the way they spend their time over a 24 hour period," says Dr Barnes, "we have been able to understand how they 'participate' and what might be done to create greater social inclusion."

The study also found that older people face barriers to participatory activities. Over one million older people experience poor social relations and social exclusion.

Spending time with friends is an important way of building social networks and support. They can be crucial for older people dealing with life-changing events such as retirement, bereavement or illness - each of which can pose an increased risk of social isolation. Spending time with people outside the household can also provide the elderly with a sense of independence.

The study found that older people who live alone spend a lot of time with friends and acquaintances, but on average, they can also spend eleven hours alone on a week day and ten and a half hours alone at weekends (excluding sleep).

Over a third of the time that older people spend with their friends is devoted to participatory activities - most often social networking such as visiting or receiving visitors, celebrating birthdays and catching up over the phone. Religious activity and doing acts of kindness involving friends are also important participatory activities.

The research also showed that women are more likely than men to spend time with friends on social networking activities. Their ability to participate, however, is limited by housework, caring for others and personal care.

"It is clear that social participation is important for an improved quality of life, both in older age and among those still working," says Dr Barnes. "Improving the accessibility of public transport and other facilities and services would go a long way towards increasing social inclusion in Britain."

These results suggest that local government and charities need to recognise that social participation is important to improve people's quality of life. "Local governments can encourage public leisure complexes and public transport services to operate wider hours or 24/7. Charities could be more aware of these groups when arranging social clubs targeting shift workers and elderly people", Dr Barnes concludes.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our psychology / psychiatry section for the latest news on this subject. The study 'Making time use explicit in an investigation of social exclusion in the UK' was carried out by Dr Matt Barnes, Lizzie Becker, John d'Souza and Andreas Cebulla of the National Centre for Social Research.
The project focused on peoples' participation in a wide range of social and civic activities to explore various aspects of exclusion. The project used the 2000 UK Time Use Survey (UKTUS) to explore the time that people spent on these activities. The UKTUS also collects a wide range of socio-demographic and economic information on individuals and their households via standard questionnaires. This information was used to identify different subgroups of the UK population.
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Study To See If Walking And/Or Memory Training May Prevent Memory Problems In People With Parkinson's Disease

Main Category: Parkinson's Disease
Also Included In: Stroke;  Rehabilitation / Physical Therapy;  Clinical Trials / Drug Trials
Article Date: 15 Dec 2011 - 0:00 PST

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Researchers from the University of Maryland School of Medicine and the Baltimore VA Medical Center have launched a study of exercise and computerized memory training to see if those activities may help people with Parkinson's disease prevent memory changes. The type of memory that will be examined is known as "executive function;" it allows people to take in information and use it in a new way. Many Parkinson's patients develop problems with executive function, which can prevent them from working and may eventually require a caregiver to take over more of the complex cognitive tasks of daily living.

"Studies of normal aging show that memory and executive function can be improved with exercise, such as walking several days a week," explains Karen Anderson, M.D., principal investigator and an assistant professor of neurology and psychiatry at the University of Maryland School of Medicine. Dr. Anderson is also a neuro-psychiatrist at the Maryland Parkinson's Disease and Movement Disorders Center at the University of Maryland Medical Center and a clinician in mental health at the Baltimore VA Medical Center.

She adds, "We want to see if exercise can slow or reverse some of these memory changes in Parkinson's patients. We will also investigate whether a computer game designed to improve executive function may make a difference as well. The other question is, what happens when you put the two interventions together - if there is memory improvement, will it be even better than with one of the interventions? Or is it more efficient to do just one or the other? We really do not know."

The researchers, who received funding through a VA Merit Award, plan to enroll about 90 patients who will be divided randomly into three groups: exercisers walking on a treadmill, memory game players and those doing both exercise and memory games. Participants in each group will receive a memory assessment at the beginning of the study. They will come in three times a week for their training for three months and will be then be tested again. Three months after that, the researchers will test the participants again to see if there may be longer term benefits to the training.

With both the treadmill walking and the memory game, the exercise or video game will become more challenging as the participant improves. The memory training works like a video game with players advancing to a higher level of difficulty. For the exercisers, trainers may increase the speed or slope of the treadmill to make it more aerobically challenging.

"This new study builds on our experience from a previous study of exercise for gait and mobility in Parkinson's disease. Since both motor function and cognitive function are important for mobility and performance of daily activities, this new study will investigate the individual and combined effects of treadmill training and cognitive training," explains Lisa Shulman, M.D., co-investigator and professor of neurology at the University of Maryland School of Medicine.

"Parkinson's patients are eager to know if there is anything they can do to give them greater control over their condition. Mobility and memory are the two key components to preserve independence. If these treatment strategies are found to be effective, we will learn important new approaches to delaying disability," says Dr. Shulman who is co-director of the Maryland Parkinson's Disease and Movement Disorders Center.

The treadmill training will take place at the Baltimore VA Medical Center in the Maryland Exercise and Robotics Center of Excellence, a gym facility with specialized equipment for people with physical limitations or balance issues. For safety, participants will wear a safety harness while walking on the treadmill. Experienced exercise physiologists will supervise each training session.

The computerized memory training game will take place both at the VA and University of Maryland School of Medicine.

"This study shows the commitment of our University of Maryland faculty to exploring new approaches, such as exercise and memory training, to help patients with illnesses such as Parkinson's disease around the world," says E. Albert Reece, M.D., Ph.D., M.B.A, vice president for medical affairs, University of Maryland, and dean, University of Maryland School of Medicine.

The Maryland researchers expanded the exercise studies to Parkinson's patients after first finding success with treadmill training for stroke patients. This research, also conducted at the University of Maryland School of Medicine and the VA Maryland Health Care System, found that regular exercise on a treadmill can improve stroke patients' walking ability even years after they've had a stroke.

Co-investigator Richard Macko, M.D., says, "With stroke patients, we have seen that the consistent, repetitive motion of walking may help the brain to develop new connections to compensate for the damaged ones. This new Parkinson's study takes the concept of exercise training for neurology patients in a new direction. We will be interested to see if this consistent training will produce benefits to memory." Dr. Macko is director of the Maryland Exercise and Robotics Center of Excellence at the VA Maryland Health Care System and professor of neurology at the University of Maryland School of Medicine.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our parkinson's disease section for the latest news on this subject. Parkinson's disease affects about one million people in the United States and Canada. Most people begin to develop symptoms in their late 50s or early 60s, although it can occur in younger people.
Parkinson's disease affects the brain's ability to produce dopamine, the neurotransmitter involved in the communication between the brain cells for motor control. Physical symptoms include tremor, muscle rigidity and slowness of movement. There are also non-motor symptoms such as changes in memory ability, sleep disturbances and depressed mood.
Parkinson's patients interested in enrolling in the exercise and memory study should call 443-827-0677.
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People With DFNA2 Hearing Loss Show Increased Touch Sensitivity

Main Category: Hearing / Deafness
Article Date: 12 Dec 2011 - 1:00 PST

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People with a certain form of inherited hearing loss have increased sensitivity to low frequency vibration, according to a study by Professor Thomas Jentsch of the Leibniz-Institut für Molekulare Pharmakologie (FMP)/Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Professor Gary Lewin (MDC), conducted in cooperation with clinicians from Madrid, Spain and Nijmegen, the Netherlands. The research findings, which were published in Nature Neuroscience *, reveal previously unknown relationships between hearing loss and touch sensitivity: In order to be able to 'feel', specialized cells in the skin must be tuned like instruments in an orchestra.

The members of the Spanish and Dutch families who participated in the study were quite amazed when the researchers from Berlin unpacked their testing equipment. Many of the family members suffer from hereditary DFNA2 hearing loss, but the researchers were less interested in their hearing ability than in their sense of touch. The hearing impairment is caused by a mutation which disrupts the function of many hair cells in the inner ear. This mutation, the researchers suspected, might also affect the sense of touch.

Tiny, delicate hairs in our inner ear vibrate to the pressure of the sound waves. The vibrations cause an influx of positively charged potassium ions into the hair cells. This electric current produces a nerve signal that is transmitted to the brain - we hear. The potassium ions flow through a channel in the cell membrane and again out of the hair cells. This potassium channel, a protein molecule called KCNQ4, is destroyed by the mutation in hearing-impaired people. The sensory cells gradually die off due to overload. "But we have found that KCNQ4 is present not only in the ear, but also in some sensory cells of the skin," Thomas Jentsch explained. "This gave us the idea that the mutation might also affect the sense of touch. And this is exactly what we were able to show in our research, which we conducted in a close collaboration with the lab of Gary Lewin, a colleague from the MDC who is specialized in touch sensation."

Whether we caress our child, search in our bag for a certain object or hold a pen in our hand - each touch conveys a variety of precise and important information about our environment. We distinguish between a rough and smooth surface by the vibrations that occur in the skin when the surface is stroked. For the different touch stimuli there are sensory cells in the skin with different structures - through the deformation of the delicate structures, electric nerve signals are generated. Exactly how this happens is still a mystery - of the five senses of Aristoteles, the sense of touch is the least understood.

Clearly there are parallels to hearing, as the findings of Matthias Heidenreich and Stefan Lechner from the research groups of Thomas Jentsch and Gary Lewin show. As a first step, the researchers in the Jentsch lab created a mouse model for deafness by generating a mouse line that carries the same mutation in the potassium channel as a patient with this form of genetic hearing loss. The touch receptors in the skin where the KCNQ4 potassium channel is found did not die off due to the defective channel like they did in the ear, but instead showed an altered electric response to the mechanical stimuli in the mutated mouse. They reacted much more sensitively to vibration stimuli in the low frequency range. The outlet valve for potassium ions normally functions here as a filter to dampen the excitability of the cells preferentially at low frequencies. This normally tunes these mechanoreceptors to moderately high frequencies in normal people. In mice lacking functional KCNQ4 channels, these receptors can no longer distinguish between low and high frequencies.

The deaf patients with mutations in the potassium channel who were examined by Stefan Lechner and Matthias Heidenreich showed exactly the same effect. They could even perceive very slow vibrations that their healthy siblings could not perceive. Due to mutations in the KCNQ4 channel gene, the fine tuning of the mechanoreceptors for normal touch sensation was altered.

The sensation of touch varies greatly from person to person - some people are much more sensitive to touch than others. DFNA2 patients are extremely sensitive to vibrations, according to Gary Lewin and Thomas Jentsch. "The skin has several different types of mechanoreceptors, which respond to different qualities of stimuli, especially to different frequency ranges. The interaction of different receptor classes is important for the touch sensation. Although the receptors we studied became more sensitive due to the loss of the potassium channel, this may be outweighed by the disadvantage of the wrong 'tuning to other frequencies'. With KCNQ4 we have for the first time identified a human gene that changes the traits of the touch sensation."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our hearing / deafness section for the latest news on this subject. The research group led by Thomas Jentsch belongs both to the FMP and the MDC in Berlin and studies ion transport and its role in disease. The group led by Gary Lewin belongs to the MDC and is specialized in peripheral sensory perception.
*KCNQ4 K+ channels tune mechanoreceptors for normal touch sensation in mouse and man. http://dx.doi.org/10.1038/nn.2985
Matthias Heidenreich1,2,9, Stefan G Lechner2,9, Vitya Vardanyan1,2,8, Christiane Wetzel2, Cor W Cremers3, Els M De Leenheer4, Gracia Aránguez5, Miguel Ángel Moreno-Pelayo6, Thomas J Jentsch1,2,7 & Gary R Lewin2,7
1Leibniz-Institut für Molekulare Pharmakologie (FMP), Berlin, Germany. 2Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany. 3Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 4Department of Otorhinolaryngology, Head and Neck Surgery, Ghent University Hospital & Ghent University, Ghent, Belgium. 5Servicio de Otorrinolaringología, Hospital General Universitario Gregorio Marañón, Madrid, Spain. 6Unidad de Genética Molecular, Hospital Ramón y Cajal, IRYCIS, CIBERER, Madrid, Spain. 7Cluster of Excellence NeuroCure, Charité-Universitätsmedizin Berlin, Berlin, Germany. 8Present address: Institute of Molecular Biology, Yerevan, Armenia. 9These authors contributed equally to this work.
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Hormone Oxytocin Makes People More Sociable, Helps Them Feel More Extroverted

Main Category: Psychology / Psychiatry
Also Included In: Endocrinology
Article Date: 12 Dec 2011 - 1:00 PST

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First dates, job interviews or Christmas cocktail parties can be stressors for some people. Such social rites of passage have no doubt made shy or introverted individuals wish for a magic potion that could make them feel like socialites, yet the answer might actually come from a nasal spray.

New research from Concordia University, published in the journal Psychopharmacology, has found that an intranasal form of oxytocin can improve self-perception in social situations. Oxytocin, a hormone naturally released following childbirth or during social bonding periods, has recently been investigated for its impact on social behaviors.

"Our study shows oxytocin can change how people see themselves, which could in turn make people more sociable," says senior author Mark Ellenbogen, Canada Research Chair in Developmental Psychopathology at Concordia University and a member of the Centre for Research in Human Development. "Under the effects of oxytocin, a person can perceive themselves as more extroverted, more open to new ideas and more trusting."

Some 100 men and women, between the ages of 18 and 35, were recruited for the study. To be eligible, participants couldn't take medication, suffer from a current or past mental disorder, use recreational drugs or smoke cigarettes.

Participants inhaled oxytocin from a nasal spray and completed questionnaires on how they felt 90 minutes later. Participants were evaluated for neuroticism, extraversion, openness to new experiences, agreeableness and conscientiousness.

"Participants who self-administered intranasal oxytocin reported higher ratings of extraversion and openness to experiences than those who received a placebo," says first author Christopher Cardoso, a graduate student in the Concordia Department of Psychology and a member of the Centre for Research in Human Development. "Specifically, oxytocin administration amplified personality traits such as warmth, trust, altruism and openness."

The study builds on previous experimental research at Concordia that has shown intranasal oxytocin can influence how people perceive their ability to cope with difficult circumstances.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our psychology / psychiatry section for the latest news on this subject. This research was funded by the Social Sciences and Humanities Research Council of Canada.
Cited study: http://www.springerlink.com/content/d48r3h445q2731t1
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Blood Pressure Medicines Reduce Stroke Risk In People With Prehypertension

Main Category: Hypertension
Also Included In: Stroke
Article Date: 12 Dec 2011 - 0:00 PST

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People with prehypertension had a lower risk of stroke when they took blood pressure-lowering medicines, according to research reported in Stroke: Journal of the American Heart Association.

Prehypertension, which affects more than 50 million adults in the United States, is blood pressure ranging between 120/80 mm Hg and 139/89 mm Hg. Hypertension is 140/90 mm Hg or higher.

"Our study pertains to people with pre-hypertensive blood pressure levels and shows that the excess risk of stroke associated with these high-normal readings (top number 120-140) can be altered by taking blood pressure pills," said Ilke Sipahi, M.D., lead author of the study and associate director of Heart Failure and Transplantation at the Harrington-McLaughlin Heart and Vascular Institute in Cleveland, Ohio.

In a meta-analysis of 16 studies, researchers examined data that compared anti-hypertensive drugs against placebo in 70,664 people with average baseline blood pressure levels within the pre-hypertensive range. The researchers found: Patients taking blood pressure-lowering medicines had a 22 percent lower risk of stroke compared to those taking a placebo. This effect was observed across all classes of anti-hypertensive drugs studied. No significant reduction in the risk of heart attack occurred, but there was a trend toward lower cardiovascular death in patients taking blood pressure medications compared to those on placebo. To prevent one stroke in the study population, 169 people had to be treated with a blood pressure-lowering medication for an average 4.3 years. American Heart Association treatment guidelines call for lifestyle changes, not medications, to reduce blood pressure in people with prehypertension. Those lifestyle changes include weight loss, physical activity, a diet rich in fruit and vegetables and low in salt and fat, and keeping alcohol consumption moderate (no more than two drinks per day for men and no more than one drink per day for women).

"We do not think that giving blood pressure medicine instead of implementing the lifestyle changes is the way to go," Sipahi said. "However, the clear-cut reduction in the risk of stroke with blood pressure pills is important and may be complementary to lifestyle changes."

The cost of long-term therapy and the risks associated with blood pressure medicines need to be discussed extensively within the medical community before undertaking guideline changes, Sipahi said.

Co-authors are: Aparna Swaminathan, fourth-year medical student; Viswanath Natesan, M.D.; Sara M. Debanne, Ph.D.; Daniel I. Simon, M.D.; and James C. Fang, M.D. Author disclosures are on the manuscript.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Potential New Therapies For People With Declining Sense Of Smell

Main Category: Ear, Nose and Throat
Also Included In: Seniors / Aging;  Neurology / Neuroscience;  Genetics
Article Date: 09 Dec 2011 - 1:00 PST

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University of California, Berkeley, neuroscientists have discovered a genetic trigger that makes the nose renew its smell sensors, providing hope for new therapies for people who have lost their sense of smell due to trauma or old age.

The gene tells olfactory stem cells the adult tissue stem cells in the nose to mature into the sensory neurons that detect odors and relay that information to the brain.

"Anosmia the absence of smell is a vastly underappreciated public health problem in our aging population. Many people lose the will to eat, which can lead to malnutrition, because the ability to taste depends on our sense of smell, which often declines with age," said lead researcher and campus neuroscientist John Ngai.

"One reason may be that as a person ages, the olfactory stem cells age and are less able to replace mature cells, or maybe they are just depleted," he said. "So, if we had a way to promote active stem cell self-renewal, we might be better able to replace these lost cells and maintain sensory function."

Gary K. Beauchamp, director of the Monell Chemical Senses Center in Philadelphia, who was not a member of the research team, noted that the olfactory system stands out for its ability to regenerate following injury or certain diseases

"This new paper ... presents an elegant analysis of some of the underlying genetic mechanisms regulating this regeneration," Beauchamp said. "It also provides important insights that should eventually allow clinicians to enhance regeneration, induce it in cases where, for currently unknown reasons, olfactory loss appears permanent, or even prevent functional loss as a person ages."

The discovery may also help scientists harness olfactory stem cells and stem cells found in other sensory systems more generally, to recover sensory function following injury or degenerative disease, said Ngai, the Coates Family Professor of Neuroscience in UC Berkeley's Department of Molecular and Cell Biology and director of the Helen Wills Neuroscience Institute and the QB3 Functional Genomics Laboratory.

Ngai, post-doctoral fellow Russell B. Fletcher and their UC Berkeley colleagues report their findings in the journal Neuron.

Self-renewal or differentiation

In the nose, smell sensory neurons live only about 30 days, then are replaced by new cells. The new cells are generated by adult stem cells in the olfactory epithelium. A key question, Ngai said, is what tells the stem cells to divide into new ones a process called self-renewal or to mature, or differentiate, into fully functional sensory nerve cells and other cells critical to maintaining olfactory function.

"These stem cells are capable of reconstituting the entire sensory epithelium of the nose following injury," Ngai said, "so understanding how these stem cells work is important for understanding the regeneration process that goes on in the nose."

Fletcher and Ngai screened nose epithelial cells for regulatory genes and discovered one, called p63, that was a previously known transcription factor that acts by controlling the transcription of other regulatory genes in epithelial stem cells, such as those in the skin, the lining of the airways and the prostate. By knocking out the p63 gene in mice, they showed that nasal olfactory stem cells rapidly differentiated into sensory neurons at the expense of the stem cells themselves.

"This gene produces a molecule that is like a brake on the stem cell," Fletcher said. "When the brake is on, stem cells self-renew. If you remove the brake, the stem cells go into differentiation."

A drug that regulates p63, or modulates one of the genes that p63, in turn, regulates, might be able to boost the number of nasal stem cells as well as the number that mature into smell neurons.

Because p63 is found in many epithelial tissues, Ngai noted, these findings could be applied to other adult tissue stem cells including stem cells in the skin and possibly lead to future therapeutic "cell replacement" strategies to take the place of damaged or dead cells not only in the nervous system but in other epihelial tissues in the body.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our ear, nose and throat section for the latest news on this subject. Coauthors with Ngai and Russell are former graduate student Melanie S. Prasol, graduate student Jose Estrada, staff professionals Ariane Baudhuin and Yoon Gi Choi, and the late Karen Vranizan of UC Berkeley's Functional Genomics Laboratory.
The research is funded by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health, UC Berkeley's Siebel Stem Cell Institute, the California Institute of Regenerative Medicine and the National Science Foundation.
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