Posts tagged science
Articles and news from the latest research reports.
In the Human Brain, Size Really Isn’t Everything
There are many things that make humans a unique species, but a couple stand out. One is our mind, the other our brain.
The human mind can carry out cognitive tasks that other animals cannot, like using language, envisioning the distant future and inferring what other people are thinking.
The human brain is exceptional, too. At three pounds, it is gigantic relative to our body size. Our closest living relatives, chimpanzees, have brains that are only a third as big.
Scientists have long suspected that our big brain and powerful mind are intimately connected. Starting about three million years ago, fossils of our ancient relatives record a huge increase in brain size. Once that cranial growth was underway, our forerunners started leaving behind signs of increasingly sophisticated minds, like stone tools and cave paintings.
But scientists have long struggled to understand how a simple increase in size could lead to the evolution of those faculties. Now, two Harvard neuroscientists, Randy L. Buckner and Fenna M. Krienen, have offered a powerful yet simple explanation.
In our smaller-brained ancestors, the researchers argue, neurons were tightly tethered in a relatively simple pattern of connections. When our ancestors’ brains expanded, those tethers ripped apart, enabling our neurons to form new circuits.
Dr. Buckner and Dr. Krienen call their idea the tether hypothesis, and present it in a paper in the December issue of the journal Trends in Cognitive Sciences.
“I think it presents some pretty exciting ideas,” said Chet C. Sherwood, an expert on human brain evolution at George Washington University who was not involved in the research.
This is how your brain tells time
Did you make it to work on time this morning? Go ahead and thank the traffic gods, but also take a moment to thank your brain. The brain’s impressively accurate internal clock allows us to detect the passage of time, a skill essential for many critical daily functions. Without the ability to track elapsed time, our morning shower could continue indefinitely. Without that nagging feeling to remind us we’ve been driving too long, we might easily miss our exit.
But how does the brain generate this finely tuned mental clock? Neuroscientists believe that we have distinct neural systems for processing different types of time, for example, to maintain a circadian rhythm, to control the timing of fine body movements, and for conscious awareness of time passage. Until recently, most neuroscientists believed that this latter type of temporal processing – the kind that alerts you when you’ve lingered over breakfast for too long – is supported by a single brain system. However, emerging research indicates that the model of a single neural clock might be too simplistic. A new study, recently published in the Journal of Neuroscience by neuroscientists at the University of California, Irvine, reveals that the brain may in fact have a second method for sensing elapsed time. What’s more, the authors propose that this second internal clock not only works in parallel with our primary neural clock, but may even compete with it.
Among Parkinson’s disease (PD) patients, female, black, and Asian patients are substantially less likely to receive proven deep brain stimulation (DBS) surgery to improve tremors and motor symptoms, according to a new report by a Perelman School of Medicine at the University of Pennsylvania researcher who identified considerable disparities among Medicare recipients receiving DBS for Parkinson’s disease. The study, published in Neurology, found that patients from neighborhoods of lower socioeconomic status were less likely to receive DBS, regardless of race or sex. And patients of minority-serving physician practices were also less likely to receive DBS, irrespective of race. The study demonstrates a need to adjust policy and incentives to provide state of the art care for all Parkinson’s patients.
Parkinson’s disease, a progressive neurodegenerative disease, affects more than 2 million Americans and cannot be prevented or halted. DBS is often prescribed for PD patients when pharmacologic treatments are unable to control involuntary movements or decrease effectiveness over time. While DBS is effective, it requires extensive pre-operative testing, is contraindicated for PD patients who have evidence of cognitive impairment or dementia, and includes out-of-pocket costs that may not be covered by Medicare. DBS out-of-pocket costs average around $2,200 (2007 dollars) per year — 41 percent more than annual non-DBS costs —and would consume approximately 7 percent of the average income in the lowest socioeconomic quartile, potentially limiting the willingness of low-income seniors to consider DBS.
"There are widespread disparities among Parkinson’s patients that are restricting equal utilization of evidence-based care, limiting patients’ quality of life, and increasing societal and health care costs," said lead study author Allison Willis, MD, Assistant Professor of Neurology and of Epidemiology at Penn Medicine. Dr. Willis collaborated on the study with colleagues from Washington University School of Medicine in St. Louis. "Efforts to overcome these disparities, through policy or reimbursement changes, can benefit elders and socioeconomically disadvantaged patients with Parkinson’s disease, as well as other vulnerable groups," said Willis.
Analyzing more than 665,000 Medicare beneficiaries with a Parkinson’s diagnosis between 2007 and 2009 - a decade after DBS was approved for Parkinson’s disease patients - the team identified 8,420 patients treated with DBS (approximately 1 percent). Nearly 95 percent of DBS recipients were white, and 59 percent were male. Hispanic PD patients were nearly equally represented among DBS (2.2 percent of all cases) and non-DBS cases (1.7 percent), whereas black and Asian populations were significantly underrepresented among DBS cases. Black PD patients accounted for 1 percent of DBS cases, and 5.5 percent of non-DBS cases, while less than 1 percent of Asian PD patients received DBS, compared to 1.5 who did not. Women of all races accounted for 41 percent of DBS cases, but 50 percent of non-DBS cases.
Patients with PD of all races who were treated by physicians with the highest concentrations of minority (Asian, Hispanic or black) patients had at least a 15 percent lower likelihood of receiving DBS, compared to providers caring for a small percentage of minority patients. While the data may not account for those who were offered DBS and refused or who were evaluated and did not qualify for DBS, the study suggests that minority-serving providers may be unlikely to perform or refer any of their Medicare beneficiaries with PD for DBS.
In addition, early data suggest that socioeconomic challenges to patients with fixed incomes may also contribute to the treatment disparities. Further research is needed to compare DBS out-of-pocket costs with standard medical and surgical procedures for other conditions.
Penn researchers will continue to study clinical characteristics and progression of disease in minorities and women, to see if they may account for any of the DBS utilization differences. In addition, they hope to look further into physician and practice characteristics along with local medical resources to determine how care differences contribute to disparities in individual DBS use.
Obesity ballooning in developing world: report
The number of obese and overweight people in the developing world nearly quadrupled to almost a billion between 1980 and 2008, a think-tank report said on Friday.
There are now far more obese or overweight adults in the developing world than in richer countries, the Overseas Development Institute (ODI) said.
The London-based institute said more than a third of all adults around the world — 1.46 billion people — were obese or overweight.
Between 1980 and 2008, the numbers of people affected in the developing world rose from 250 million to 904 million. In the developed world, the figure rose from 321 million to 557 million.
This represented a rise from 23 percent to 34 percent of the world population.
"The growing rates of overweight and obesity in developing countries are alarming," said ODI research fellow Steve Wiggins, who co-authored the Future Diets report.
"On current trends, globally, we will see a huge increase in the number of people suffering certain types of cancer, diabetes, strokes and heart attacks, putting an enormous burden on public healthcare systems."
The report said overweight and obesity rates have almost doubled in China and Mexico since 1980, and risen by a third in South Africa.
The study said the rise in obesity was down to diets changing in developing countries where incomes were rising, with people shifting away from cereals and tubers to eating more meat, fats and sugar.
The over-consumption of food, coupled with increasingly sedentary lives, was also to blame.
The report found that North Africa, the Middle East and South America saw overweight and obesity rates increase to a level similar to Europe, around 58 percent.
At 70 percent, North America still has the highest percentage of overweight adults.
The report said there seemed to be little will among the public and leaders to take action on influencing diet in the future.
"Governments have focused on public awareness campaigns, but evidence shows this is not enough," said Wiggins.
"The lack of action stands in stark contrast to the concerted public actions taken to limit smoking in developed countries.
"Politicians need to be less shy about trying to influence what food ends up on our plates. The challenge is to make healthy diets viable whilst reducing the appeal of foods which carry a less certain nutritional value."
The report gave the example of South Korea as having made efforts to preserve healthy elements of the country’s traditional diet, via public campaigns and education, providing large-scale training for women in preparing healthy, traditional food.
The report said it was “only a matter of time” before people would begin to accept and even demand stronger and more effective measures to influence diets.
Loss of function of a single gene linked to diabetes in mice
Researchers from the University of Illinois at Chicago College of Medicine have found that dysfunction in a single gene in mice causes fasting hyperglycemia, one of the major symptoms of type 2 diabetes. Their findings were reported online in the journal Diabetes.
If a gene called MADD is not functioning properly, insulin is not released into the bloodstream to regulate blood sugar levels, says Bellur S. Prabhakar, professor and head of microbiology and immunology at UIC and lead author of the paper.
Type 2 diabetes affects roughly 8 percent of Americans and more than 366 million people worldwide. It can cause serious complications, including cardiovascular disease, kidney failure, loss of limbs and blindness.
In a healthy person, beta cells in the pancreas secrete the hormone insulin in response to increases in blood glucose after eating. Insulin allows glucose to enter cells where it can be used as energy, keeping glucose levels in the blood within a narrow range. People with type 2 diabetes don’t produce enough insulin or are resistant to its effects. They must closely monitor their blood glucose throughout the day and, when medication fails, inject insulin.
In previous work, Prabhakar isolated several genes from human beta cells, including MADD, which is also involved in certain cancers. Small genetic variations found among thousands of human subjects revealed that a mutation in MADD was strongly associated with type 2 diabetes in Europeans and Han Chinese.
People with this mutation had high blood glucose and problems of insulin secretion – the “hallmarks of type 2 diabetes,” Prabhakar said. But it was unclear how the mutation was causing the symptoms, or whether it caused them on its own or in concert with other genes associated with type 2 diabetes.
To study the role of MADD in diabetes, Prabhakar and his colleagues developed a mouse model in which the MADD gene was deleted from the insulin-producing beta cells. All such mice had elevated blood glucose levels, which the researchers found was due to insufficient release of insulin.
“We didn’t see any insulin resistance in their cells, but it was clear that the beta cells were not functioning properly,” Prabhakar said. Examination of the beta cells revealed that they were packed with insulin. “The cells were producing plenty of insulin, they just weren’t secreting it,” he said.
The finding shows that type 2 diabetes can be directly caused by the loss of a properly functioning MADD gene alone, Prabhakar said. “Without the gene, insulin can’t leave the beta cells, and blood glucose levels are chronically high.”
Prabhakar now hopes to investigate the effect of a drug that allows for the secretion of insulin in MADD-deficient beta cells.
“If this drug works to reverse the deficits associated with a defective MADD gene in the beta cells of our model mice, it may have potential for treating people with this mutation who have an insulin-secretion defect and/or type 2 diabetes,” he said.
(Source: news.uic.edu)
Stimulating brain cells stops binge drinking, animal study finds
Researchers at the University at Buffalo have found a way to change alcohol drinking behavior in rodents, using the emerging technique of optogenetics, which uses light to stimulate neurons.
Their work could lead to powerful new ways to treat alcoholism, other addictions, and neurological and mental illnesses; it also helps explain the underlying neurochemical basis of drug addiction.
The findings, published in November in Frontiers in Neuroscience, are the first to demonstrate a causal relationship between the release of dopamine in the brain and drinking behaviors of animals. Research like this, which makes it possible to map the neuronal circuits responsible for specific behaviors, is a major focus of President Obama’s Brain Research for Advancing Innovative Neurotechnologies initiative, known as BRAIN.
In the experiments, rats were trained to drink alcohol in a way that mimics human binge-drinking behavior.
First author Caroline E. Bass, PhD, assistant professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences explains: “By stimulating certain dopamine neurons in a precise pattern, resulting in low but prolonged levels of dopamine release, we could prevent the rats from binging. The rats just flat out stopped drinking,” she says.
Bass’s co-authors are at Wake Forest University, where she worked previously.
Interestingly, the rodents continued to avoid alcohol even after the stimulation of neurons ended, she adds.
“For decades, we have observed that particular brain regions light up or become more active in an alcoholic when he or she drinks or looks at pictures of people drinking, for example, but we didn’t know if those changes in brain activity actually governed the alcoholic’s behavior,” says Bass.
The researchers activated the dopamine neurons through a type of deep brain stimulation, but unlike techniques now used to treat certain neurological disorders, such as severe tremors in Parkinson’s disease patients, this new technique, called optogenetics, uses light instead of electricity to stimulate neurons.
“Electrical stimulation doesn’t discriminate,” Bass explains. “It hits all the neurons, but the brain has many different kinds of neurons, with different neurotransmitters and different functions. Optogenetics allows you to stimulate only one type of neuron at a time.”
Bass specializes in using viral vectors to study the brain in substance abuse. In this study, she used a virus to introduce a gene encoding a light-responsive protein into the animals’ brains. That protein then activated a specific subpopulation of dopamine neurons in the brain’s reward system.
“I created a virus that will make this protein only in dopaminergic neurons,” Bass says.
The neuronal pathways affected in this research are involved in many neurological disorders, she says. For that reason, the results have application not only in understanding and treating alcohol-drinking behaviors in humans, but also in many devastating mental illnesses and neurological diseases that have a dopamine component.
Bass notes that this ability to target genes to dopamine neurons could potentially lead to the use of gene therapy in the brain to mitigate many of these disorders.
“We can target dopamine neurons in a part of the brain called the nigrostriatal pathway, which is what degenerates in Parkinson’s disease,” she says. “If we could infuse a viral vector into that part of the brain, we could target potentially therapeutic genes to the dopamine neurons involved in Parkinson’s. And by infusing the virus into other areas of the brain, we could potentially deliver therapeutic genes to treat other neurological diseases and mental illnesses, including schizophrenia and depression.”
Researchers report technique that enables patient with ‘word blindness’ to read again
In the journal Neurology, researchers report a novel technique that enables a patient with “word blindness” to read again.
Word blindness is a rare neurological condition. (The medical term is “alexia without agraphia.”) Although a patient can write and understand the spoken word, the patient is unable to read.
The article is written by Jason Cuomo, Murray Flaster, MD, PhD and Jose Biller, MD, of Loyola University Medical Center.
Here’s how the technique works: When shown a word, the patient looks at the first letter. Although she clearly sees it, she cannot recognize it. So beginning with the letter A, she traces each letter of the alphabet over the unknown letter until she gets a match. For example, when shown the word Mother, she will trace the letters of the alphabet, one at a time, until she comes to M and finds a match. Three letters later, she guesses correctly that the word is Mother.
"To see this curious adaption in practice is to witness the very unique and focal nature" of the deficit, the authors write.
The authors describe how word blindness came on suddenly to a 40-year-old kindergarten teacher and reading specialist. She couldn’t make sense of her lesson plan, and her attendance sheet was as incomprehensible as hieroglyphs. She also couldn’t tell time.
The condition was due to a stroke that probably was caused by an unusual type of blood vessel inflammation within the brain called primary central nervous system angiitis.
Once a passionate reader, she was determined to learn how to read again. But none of the techniques that she had taught her students – phonics, sight words, flash cards, writing exercises, etc. – worked. So she taught herself a remarkable new technique that employed tactile skills that she still possessed.
The woman can have an emotional reaction to a word, even if she can’t read it. Shown the word “dessert,” she says “Oooh, I like that.” But when shown “asparagus,” she says, “Something’s upsetting me about this word.”
Shown two personal letters that came in the mail, she correctly determined which was sent by a friend of her mother’s and which was sent by one of her own friends. “When asked who these friends were, she could not say, but their names nevertheless provoked an emotional response that served as a powerful contextual clue,” the authors write.
What she most misses is reading books to children. She teared up as she told the authors: “One day my mom was with the kids in the family, and they were all curled up next to each other, and they were reading. And I started to cry, because that was something I couldn’t do.”
(Source: eurekalert.org)
Brain training works, but just for the practiced task
Search for “brain training” on the Web. You’ll find online exercises, games, software, even apps, all designed to prepare your brain to do better on any number of tasks. Do they work? University of Oregon psychologists say, yes, but “there’s a catch.”
The catch, according to Elliot T. Berkman, a professor in the Department of Psychology and lead author on a study published in the Jan. 1 issue of the Journal of Neuroscience, is that training for a particular task does heighten performance, but that advantage doesn’t necessarily carry over to a new challenge.
The training provided in the study caused a proactive shift in inhibitory control. However, it is not clear if the improvement attained extends to other kinds of executive function such as working memory, because the team’s sole focus was on inhibitory control, said Berkman, who directs the psychology department’s Social and Affective Neuroscience Lab.
"With training, the brain activity became linked to specific cues that predicted when inhibitory control might be needed," he said. "This result is important because it explains how brain training improves performance on a given task — and also why the performance boost doesn’t generalize beyond that task."
Sixty participants (27 male, 33 females and ranging from 18 to 30 years old) took part in a three-phase study. Change in their brain activity was monitored with functional magnetic resonance imaging (fMRI).
Half of the subjects were in the experimental group that was trained with a task that models inhibitory control — one kind of self-control — as a race between a “go” process and a “stop” process. A faster stop process indicates more efficient inhibitory control.
In each of a series of trials, participants were given a “go” signal — an arrow pointing left or right. Subjects pressed a key corresponding to the direction of the arrow as quickly as possible, launching the go process. However, on 25 percent of the trials, a beep sounded after the arrow appeared, signaling participants to withhold their button press, launching the stop process.
Participants practiced either the stop-signal task or a control task that didn’t affect inhibitory control every other day for three weeks. Performance improved more in the training group than in the control group.
Neural activity was monitored using functional magnetic resonance imaging (fMRI), which captures changes in blood oxygen levels, during a stop-signal task. MRI work was done in the UO’s Robert and Beverly Lewis Center for Neuroimaging. Activity in the inferior frontal gyrus and anterior cingulate cortex — brain regions that regulate inhibitory control — decreased during inhibitory control but increased immediately before it in the training group more than in the control group.
The fMRI results identified three regions of the brain of the trained subjects that showed changes during the task, prompting the researchers to theorize that emotional regulation may have been improved by reducing distress and frustration during the trials. Overall, the size of the training effect is small. A challenge for future research, they concluded, will be to identify protocols that might generate greater positive and lasting effects.”Researchers at the University of Oregon are using tools and technologies to shed new light on important mechanisms of cognitive functioning such as executive control,” said Kimberly Andrews Espy, vice president for research and innovation and dean of the UO Graduate School. “This revealing study on brain training by Dr. Berkman and his team furthers our understanding of inhibitory control and may lead to the design of better prevention tools to promote mental health.”
Molecule discovered that protects the brain from cannabis intoxication
Two INSERM research teams led by Pier Vincenzo Piazza and Giovanni Marsicano (INSERM Unit 862 “Neurocentre Magendie” in Bordeaux) recently discovered that pregnenolone, a molecule produced by the brain, acts as a natural defence mechanism against the harmful effects of cannabis in animals. Pregnenolone prevents THC, the main active principle in cannabis, from fully activating its brain receptor, the CB1 receptor, that when overstimulated by THC causes the intoxicating effects of cannabis. By identifying this mechanism, the INSERM teams are already developing new approaches for the treatment of cannabis addiction.
These results are to be published in Science on 3 January.
Over 20 million people around the world are addicted to cannabis, including a little more than a half million people in France. In the last few years, cannabis addiction has become one of the main reasons for seeking treatment in addiction clinics. Cannabis consumption is particularly high (30%) in individuals between 16 to 24 years old, a population that is especially susceptible to the harmful effects of the drug.
While cannabis consumers are seeking a state of relaxation, well-being and altered perception, there are many dangers associated to a regular consumption of cannabis. Two major behavioural problems are associated with regular cannabis use in humans: cognitive deficits and a general loss of motivation. Thus, in addition to being extremely dependent on the drug, regular users of cannabis show signs of memory loss and a lack of motivation that make quite hard their social insertion.
The main active ingredient in cannabis, THC, acts on the brain through CB1 cannabinoid receptors located in the neurons. THC binds to these receptors diverting them from their physiological roles, such as regulating food intake, metabolism, cognitive processes and pleasure. When THC overstimulates CB1 receptors, it triggers a reduction in memory abilities, motivation and gradually leads to dependence.
Increase of dopamine release
Developing an efficient treatment for cannabis addiction is becoming a priority of research in the fiend of drug addiction.
In this context, the INSERM teams led by Pier Vincenzo Piazza and Giovanni Marsicano have investigated the potential role of pregnenolone a brain produced steroid hormone. Up to now, pregnenolone was considered the inactive precursor used to synthesize all the other steroid hormones (progesterone, estrogens, testosterone, etc.). The INSERM researchers have now discovered that pregnenolone has quite an important functional role: it provide a natural defence mechanism that can protect the brain from the harmful effects of cannabis.
Essentially, when high doses of THC (well above those inhaled by regular users) activate the CB1 cannabinoid receptor they also trigger the synthesis of pregnenolone. Pregnenole then binds to a specific site on the same CB1 receptors (see figure) and reducing the effects of THC.
The administration of pregnenolone at doses that increase the brain’s level of this hormone even more, antagonize the behavioral effects of cannabis.
At the neurobiological level, pregnenolone greatly reduces the release of dopamine triggered by THC. This is an important effect, since the addictive effects of drugs involve an excessive release of dopamine.
This negative feedback mediated by pregnenolone (THC is what triggers the production of pregnenolone, which then inhibits the effects of THC) reveal a previously unknown endogenous mechanism that protects the brain from an over-activation of CB1 receptor.
A protective mechanism that opens the doors to a new therapeutic approach.
The role of pregnenolone was discovered when, rats were given equivalent doses of cocaine, morphine, nicotine, alcohol and cannabis and the levels of several brain steroids (pregnenolone, testosterone, allopregnenolone, DHEA etc..) were measured. It was then found that only one drug, THC, increased brain steroids and more specifically selectively one steroid, pregnenolone, that went up3000% for a period of two hours.
The effect of administering THC on the pregnenolone synthesis (PREG) and other brain steroids
This increase in pregnenolone is a built-in mechanism that moderates the effects of THC. Thus, the effects of THC increase when pregnenolone synthesis is blocked. Conversely, when pregnenolone is administered to rats or mice at doses (2-6 mg/kg) that induce even greater concentrations of the hormone in the brain, the negative behavioural effects of THC are blocked. For example, the animals that were given pregnenolone recover their normal memory abilities, are less sedated and less incline to self-administer cannabinoids.
Experiments conducted in cell cultures that express the human CB1 receptor confirm that pregnenolone can also counteract the molecular action of THC in humans.
Pier Vincenzo Piazza explains that pregnenolone itself cannot be used as a treatment “Pregnenolone cannot be used as a treatment because it is badly absorbed when administerd orally and once in the blood stream it is rapidly transformed in other steroids”.
However, the researcher says that there is strong hope of seeing a new addiction therapy emerge from this discovery. “We have now developed derivatives of pregnenolone that are well absorbed and stable. They then present the characteristics of compounds that can be used as new class of therapeutic drugs. We should be able to begin clinical trials soon and verify whether we have indeed discovered the first pharmacological treatment for cannabis dependence.”
Odor receptors discovered in lungs
Your nose is not the only organ in your body that can sense cigarette smoke wafting through the air. Scientists at Washington University in St. Louis and the University of Iowa have shown that your lungs have odor receptors as well.
Unlike the receptors in your nose, which are located in the membranes of nerve cells, the ones in your lungs are in the membranes of neuroendocrine cells. Instead of sending nerve impulses to your brain that allow it to “perceive” the acrid smell of a burning cigarette somewhere in the vicinity, they trigger the flask-shaped neuroendocrine cells to dump hormones that make your airways constrict.
The newly discovered class of cells expressing olfactory receptors in human airways, called pulmonary neuroendocrine cells, or PNECs, were found by a team led by Yehuda Ben-Shahar, PhD, assistant professor of biology, in Arts & Sciences, and of medicine at Washington University in St. Louis, and including colleagues Steven L. Brody, MD, and Michael J. Holtzman, MD, of the Washington University School of Medicine, and Michel J. Welsh, MD, of the University of Iowa Carver College of Medicine.
“We forget,” said Ben-Shahar, “that our body plan is a tube within a tube, so our lungs and our gut are open to the external environment. Although they’re inside us, they’re actually part of our external layer. So they constantly suffer environmental insults,” he said, “and it makes sense that we evolved mechanisms to protect ourselves.”
In other words, the PNECs, described in the March issue of the American Journal of Respiratory Cell and Molecular Biology, are sentinels, guards whose job it is to exclude irritating or toxic chemicals.
The cells might be responsible for the chemical hypersensitivity that characterizes respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Patients with these diseases are told to avoid traffic fumes, pungent odors, perfumes and similar irritants, which can trigger airway constriction and breathing difficulties.
The odor receptors on the cells might be a therapeutic target, Ben-Shahar suggests. By blocking them, it might be possible to prevent some attacks, allowing people to cut down on the use of steroids or bronchodilators.
Every breath you take
When a mammal inhales, volatile chemicals flow over two patches of specialized epithelial tissue high up in the nasal passages. These patches are rich in nerve cells with specialized odorant-binding molecules embedded in their membranes.
If a chemical docks on one of these receptors, the neuron fires, sending impulses along the olfactory nerve to the olfactory bulb in the brain, where the signal is integrated with those from hundreds of other similar cells to conjure the scent of old leather or dried lavender.
Aware that airway diseases are characterized by hypersensitivity to volatile stimuli, Ben-Shahar and his colleagues realized that the lungs, like the nose, must have some means of detecting inhaled chemicals.
Earlier, a team at the University of Iowa, where Ben-Shahar was a postdoctoral research associate, had searched for genes expressed by patches of tissue from lung transplant donors. They found a group of ciliated cells that express bitter taste receptors. When offending substances were detected, the cilia beat more strongly to sweep them out of the airway. This result was featured on the cover of the Aug. 28, 2009, issue of Science.
But since people are sensitive to many inhaled substances, not just bitter ones, Ben-Shahar decided to look again. This time he found that these tissues also express odor receptors, not on ciliated cells but instead on neuroendocrine cells, flask-shaped cells that dump serotonin and various neuropeptides when they are stimulated.
This made sense. “When people with airway disease have pathological responses to odors, they’re usually pretty fast and violent,” said Ben-Shahar. “Patients suddenly shut down and can’t breathe, and these cells may explain why.”
Ben-Shahar stresses the differences between chemosensation in the nose and in the lung. The cells in the nose are neurons, he points out, each with a narrowly tuned receptor, and their signals must be woven together in the brain to interpret our odor environment.
The cells in the airways are secretory, not neuronal, cells, and they may carry more than one receptor, so they are broadly tuned. Instead of sending nerve impulses to the brain, they flood local nerves and muscles with serotonin and neuropeptides. “They are possibly designed,” he said, “to elicit a rapid, physiological response if you inhale something that is bad for you.”
The different mechanisms explain why cognition plays a much stronger role in taste and smell than in coughing in response to an irritant. It is possible, for example, to develop a taste for beer. But nobody learns not to cough; the response is rapid and largely automatic.
The scientists suspect these pulmonary neuroscretory cells contribute to the hypersensitivity of patients with COPD to airborne irritants. COPD is a group of diseases, including emphysema, that is characterized by coughing, wheezing, shortness of breath and chest tightness.
When the scientists looked at the airway tissues from patients with COPD, they discovered that they had more of these neurosecretory cells than airway tissues from healthy donors.
Of mice and men
As a geneticist, Ben-Shahar would like to go farther, knocking out genes to make sure that the derangement of neurosecretory cells isn’t just correlated with airway diseases but instead suffices to produce it.
But there is a problem. “For example, a liver from a mouse and a liver from a human are pretty similar, they express the same types of cells. But the lungs from different mammalian species are often very different; you can see it at a glance,” Ben-Shahar said.
“Clearly, primates have evolved distinct cell lineages and signaling systems for respiratory-specific functions.”
This makes it challenging to unravel the biomolecular mechanisms of respiratory diseases.
Still, he is hopeful that the PNEC pathways will provide targets for drugs that would better control asthma, COPD and other respiratory diseases. They would be welcome. There has been a steep rise in these diseases in the past few decades, treatment options have been limited, and there are no cures.