Neuroscience, Dopamine and Vern Den Herder

Coming to a late night infomercial near you….

Neurotransmitter got ya down?

At the law offices of Jose Garcia & Cy Rabinowitz, we’ll fight for your rights to recall your enemies….

I keep expecting the type of advances discussed in optimistic magazine articles about neuroscience to always be down the road. The wait is over. In this Sunday’s NYT, see the article about ongoing genetic testing. The testing described involves the ACTN3 gene, which is tied to athletic performance. I started this post with a joke about lawyers, but it’s not hard to see a few years down the road if the ACTN3 gene’s athletic connection turns out to have been incorrect, some parent suing for wasted swim lessons for Johnny. The liability / disclaimer forms associated with the testing must be a Georgia-Pacific wet dream.

Speaking of where all this is going. Another article that day dealt with Gay rights groups protesting the California amendment which passed and excludes homosexuals from obtaining a formal marriage designation. The gay gene. At this point it appears to be a when, not if, they identify it. The first and most obvious ramification will be parents who wish to ensure that their child does not have that gene. But how about if a gay couple hires a surrogate mom and attempts to ensure that the child–the term ‘fetus’ is only applicable when people wish to kill it–have the gay gene. Who complains in scenario A? Who complains in scenario B? Who will be consistent on the issue? I am against the idea of DNA manipulation, i.e. playing God. But what if the gene manipulation pertains to avoiding a disease?

Then in Tuesday’s WSJ, an article about ongoing testing to determine the origins of senior moments. It turns out that there is this biochemical called dopamine, which is associated with adrenaline, the absence of which allows us to relax [and forget things] as we age. However, if we lose too much, we are susceptible to Parkinson’s.

I note all this as I doggedly attempt–determined for now not to google it–to recall Vern Den Herder’s jersey number, since ‘vdenherder’ was one of my password clues for the online Comcast account which I apparently once setup.

Hey quit you’re smirking about Den Herder. He is a member of the College Football Hall of Fame and in 12 seasons for the Dolphins, he played in three Super Bowls and went to a Pro Bowl.

All articles referenced are copied in full at end of post.

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Biochemicals

Amino Acids — The fundamental building blocks of proteins and also an important class of biochemicals involved in intermediary metabolism.

Cholesterol — Can’t live with it, can’t live without it. This important steroid serves as the precursor to an entire lineup of essential steroids.

DNA — The hard drive of the human body. This complex biopolymer is the storage site for genetic information.

Fatty Acids — Long chained biochemicals that store food energy until it is needed. These molecules are also involved in a variety of biological functions.

Hormones — Probably our biggest problems derive from increased blood levels of certain hormones. Once again, can’t live with ‘em, but can’t live without ‘em either.

Minerals — A collection of bioessential salts that are used in a huge number of biochemical metabolic pathways.

Neurotransmitters — Small biochemicals that our body uses to shuttle messages from one part to another. Often these guys are the target of abusive chemicals and drugs.

Phytochemicals — The “vitamins” of the next millennium, these chemicals are mostly derived from plants. There is a growing body of evidence that many of these biochemicals can stop cancer.

Prostaglandins — Bioactive lipids that act in a manner similar to hormones, although on a more localized basis. These chemicals are synthesized and degraded very rapidly.

Proteins — Important biopolymers that play a critical role in the structure and function of the body. This class of biochemicals includes enzymes, collagen, and hemoglobin, to name a few.

Sugars — An important food source for the brain. These biochemicals are involved in a vast number of important pathways and are also commonly used as structural components of proteins, enzymes, and cell walls.

Vitamins — Derived from the term “vital amines”, these essential biochemicals must be obtained in the diet. They are responsible for catalyzing some of the most complex biosynthesis in the body.
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Surveying the Brain for Origins of the Senior Moment

DECEMBER 2, 2008

Aging Brings Mental Changes — Including a Slowdown of Mere Milliseconds — That Drive Us to Distraction

By ROBERT LEE HOTZ

SAN FRANCISCO — Nyla Puccinelli sat patiently at the crossroads of memory, attention and aging, while a lab technician threaded color-coded electrodes into the mesh cap on her head. A retired school teacher, she’d always had trouble recalling her students’ names but she worried more now about her memory and found it harder to shrug off distractions.

“If I am really concentrating on something now, I have to turn off the radio,” Ms. Puccinelli, 69 years old, said. “There is a lack of concentration. Because you’re getting older, you get more concerned about it.”

By recording the electrical activity of her mind at work, neurologist Adam Gazzaley at the University of California at San Francisco was using her healthy brain as a road map of mental changes that age brings to us all. In particular, Dr. Gazzaley and his colleagues were trying to understand why aging drives us all to distraction.

At the slightest interruption — an irritating ring tone, an insistent email alert or the hushed conversation in the adjacent office cubicle — our thoughts can plunge into the mental underbrush like hounds snuffling after the wrong scent. As scientists document the normal brain changes at fault, they are highlighting a growing conflict between the push-me-pull-you demands of modern multitasking and our waning powers of concentration. By one estimate, the average office worker is interrupted every three minutes. Indeed, our inability to ignore irrelevant intrusions as we grow older may arise from a basic breakdown of internal brain communications involving memory, attention span and mental focus starting in middle age, researchers have discovered.

These days, we look for any insight into how aging alters the brain. “My patients are most worried about having something go wrong with their brain as they age, more than they worry about cancer,” says clinical neuropsychologist Karen Berman at the National Institute of Mental Health.

America’s 78 million baby boomers are turning 60 at the rate of about 8,000 a day. By 2050, the world’s population of those over 60 years old is expected to exceed the number of young people for the first time in history, according to the United Nations population division, with more than 2 billion people potentially prone to absent-minded moments of memory lapse and befuddlement.

“It is a public health issue — the aging mind — but more than that, it is an individual issue for so many people,” says Dr. Gazzaley. “People don’t want to retire. They want to compete in the workplace as well as they ever did, as well as the 20-year-old who was just hired in the room next to them. People want their brain to be the same their whole life.”

No matter what we do, though, our brains normally shrink as we age — a man’s faster than a woman’s — affecting regions associated with learning and memory. Many genes linked to brain function in the prefrontal cortex also become less active, affecting how deftly we can orchestrate thoughts and actions.

By combining different measures of brain activity — positron emission tomography, functional magnetic resonance imaging and electro-encephalography — scientists for the first time can see how aging brain regions, designed to work in unison like the interlocking innards of an expensive watch, fail to mesh swiftly and smoothly. Normal aging, for example, disrupts the electrical crosstalk between major brain regions, researchers at Harvard University reported last December in the journal Neuron.

“With these new physiological techniques, we can look at what is going on the brain when you are supposed to be ignoring something,” Dr. Gazzaley says.

Among the brain circuits that focus attention and memory, his research suggests, aging is a matter of milliseconds. In experiments testing how well people of different ages could recall faces and landscapes, Dr. Gazzaley and scientists at UC Berkeley found that among older people, the brain was slightly slower — 200 milliseconds or so — to ignore irrelevant test information. That instant of interference was enough to disrupt a memory in the making, they found.

“This is the distractibility,” he says. In fact, it significantly affected how well older people did on memory tests compared to younger adults. “In that first fraction of a second, younger adults are much better at blocking things out,” Dr. Gazzaley said.

During that momentary lapse, we can forget a new name, misplace our keys or lose our train of thought.
Brain Teaser

Test your ability to tune out distractions on the interactive “Remembering Faces” quiz, at National Public Radio, developed by neurologist Adam Gazzaley at the University of California at San Francisco to test memory and attention.
Recommended Reading

Dr. Gazzaley reported on recent experiments revealing how normal aging affects memory and attention in The Proceedings of the National Academy of Sciences and in Nature Neuroscience.

Psychologist Cindy Lustig at the University of Michigan’s cognition and aging laboratory and her colleagues surveyed current research on aging and cognition in “Brain aging: Reorganizing discoveries about the aging mind” published in the journal Current Opinion in Neurobiology.

Dr. Karen Berman at the National Institute of Mental Health and her colleagues reported on how a healthy brain mellows with age in “Age-related changes in midbrain dopaminergic regulation of the human reward system.”

Harvard University neuroscientist Daniel L. Schacter writes broadly on the foibles of memory in two books: The Seven Sins of Memory: How the Mind Forgets and Remembers, which received a New York Times Notable Book of the Year Award, and Searching for Memory, which won the American Psychological Association’s William James Book Award.

Moreover, our brains start changing long before we can see the pattern in such shortcomings. Last month, researchers at UCLA reported that, beginning in middle age, we start to lose the myelin insulation that sheathes the nerve fibers running through our frontal lobes. In essence, the electrical wires of our neural circuits begin to fray and that could imperceptibly hamper our thought process. In 2006, scientists at the University of Toronto and the Rotman Research Institute in Canada reported that, among people in their 40s, they already could detect the neural mismatches that make many of us more vulnerable to distractions.

By the time we reach age 65 or more, one fourth of us may be wrestling with a failing memory and other mild cognitive problems, researchers at the Indiana School of Medicine reported in the journal Neurology. An 88-year-old widow described the feeling. “My brain argues with itself,”‘ she says. “Spontaneous thoughts can be a struggle because they keep dancing off. They don’t all march along at the same speed. It’s very annoying.”

Not all the indignities of age are inevitable, research suggests. “Yes, there are biological brain changes; yes, things get harder; but we seem to be able to compensate for that,” says University of Michigan psychologist Cindy Lustig, who studies how mental abilities change with age.

To keep mentally fit, a generation of aging gym rats has embraced the cognitive calisthenics of computerized brain exercises. Not all mental gymnastics or herbal supplements work as advertised, but proper diet, cardiovascular exercise and formal education do stave off mental decline, according to new research. “With the right kind of training, we can take an older mind and make it younger,” Dr. Gazzaley says. “The potential exists.”

Something seems to be working. Earlier this year, researchers at the University of Michigan reported that, in a study of 11,000 retired people, memory loss and other cognitive problems were becoming less common among older Americans. That could be due to better care of high blood pressure, cholesterol and other medical risk factors. No one is sure. An active social life also appears to slow the rate at which memory fails, researchers at the Harvard School of Public Health reported this past July in the American Journal of Public Health.

Despite its distractions, a healthy brain may also mellow with age. The roller-coaster rush of dopamine, a biochemical associated with heady feelings of reward, doesn’t affect older people as strongly as it does the young, Dr. Berman reported this fall in the Proceedings of the National Academy of Sciences.

Is this evidence that, among older neurons and synapses, life can lose its savor? “I would suggest it shows that older people are appreciating life in a different way,” says Dr. Berman.

In other words, the dopamine drop may be a biochemical marker of something else: the wisdom to accept with grace what we cannot change.
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Born to Run? Little Ones Get Test for Sports Gene

November 30, 2008

By JULIET MACUR

BOULDER, Colo. — When Donna Campiglia learned recently that a genetic test might be able to determine which sports suit the talents of her 2 ½-year-old son, Noah, she instantly said, Where can I get it and how much does it cost?

“I could see how some people might think the test would pigeonhole your child into doing fewer sports or being exposed to fewer things, but I still think it’s good to match them with the right activity,” Ms. Campiglia, 36, said as she watched a toddler class at Boulder Indoor Soccer in which Noah struggled to take direction from the coach between juice and potty breaks.

“I think it would prevent a lot of parental frustration,” she said.

In health-conscious, sports-oriented Boulder, Atlas Sports Genetics is playing into the obsessions of parents by offering a $149 test that aims to predict a child’s natural athletic strengths. The process is simple. Swab inside the child’s cheek and along the gums to collect DNA and return it to a lab for analysis of ACTN3, one gene among more than 20,000 in the human genome.

The test’s goal is to determine whether a person would be best at speed and power sports like sprinting or football, or endurance sports like distance running, or a combination of the two. A 2003 study discovered the link between ACTN3 and those athletic abilities.

In this era of genetic testing, DNA is being analyzed to determine predispositions to disease, but experts raise serious questions about marketing it as a first step in finding a child’s sports niche, which some parents consider the road to a college scholarship or a career as a professional athlete.

Atlas executives acknowledge that their test has limitations but say that it could provide guidelines for placing youngsters in sports. The company is focused on testing children from infancy to about 8 years old because physical tests to gauge future sports performance at that age are, at best, unreliable.

Some experts say ACTN3 testing is in its infancy and virtually useless. Dr. Theodore Friedmann, the director of the University of California-San Diego Medical Center’s interdepartmental gene therapy program, called it “an opportunity to sell new versions of snake oil.”

“This may or may not be quite that venal, but I would like to see a lot more research done before it is offered to the general public,” he said. “I don’t deny that these genes have a role in athletic success, but it’s not that black and white.”

Dr. Stephen M. Roth, director of the functional genomics laboratory at the University of Maryland’s School of Public Health who has studied ACTN3, said he thought the test would become popular. But he had reservations.

“The idea that it will be one or two genes that are contributing to the Michael Phelpses or the Usain Bolts of the world I think is shortsighted because it’s much more complex than that,” he said, adding that athletic performance has been found to be affected by at least 200 genes.

Dr. Roth called ACTN3 “one of the most exciting and eyebrow-raising genes out there in the sports-performance arena,” but he said that any test for the gene would be best used only on top athletes looking to tailor workouts to their body types.

“It seems to be important at very elite levels of competition,” Dr. Roth said. “But is it going to affect little Johnny when he participates in soccer, or Suzy’s ability to perform sixth grade track and field? There’s very little evidence to suggest that.”

The study that identified the connection between ACTN3 and elite athletic performance was published in 2003 by researchers primarily based in Australia.

Those scientists looked at the gene’s combinations, one copy provided by each parent. The R variant of ACTN3 instructs the body to produce a protein, alpha-actinin-3, found specifically in fast-twitch muscles. Those muscles are capable of the forceful, quick contractions necessary in speed and power sports. The X variant prevents production of the protein.

The ACTN3 study looked at 429 elite white athletes, including 50 Olympians, and found that 50 percent of the 107 sprint athletes had two copies of the R variant. Even more telling, no female elite sprinter had two copies of the X variant. All male Olympians in power sports had at least one copy of the R variant.

Conversely, nearly 25 percent of the elite endurance athletes had two copies of the X variant — only slightly higher than the control group at 18 percent. That means people with two X copies are more likely to be suited for endurance sports.

Still, some athletes prove science, and seemingly their genetics, wrong. Research on an Olympic long jumper from Spain showed that he had no copies of the R variant, indicating that athletic success is probably affected by a combination of genes as well as factors like environment, training, nutrition and luck.

“Just think if that Spanish kid’s parents had done the test and said, ‘No, your genes show that you are going to be a bad long jumper, so we are going to make you a golfer,’ ” said Carl Foster, a co-author of the study, who is the director of the human performance laboratory at the University of Wisconsin-La Crosse. “Now look at him. He’s the springiest guy in Spain. He’s Tigger. We don’t yet understand what combination of genes creates that kind of explosiveness.”

Dr. Foster suggested another way to determine if a child will be good at sprint and power sports. “Just line them up with their classmates for a race and see which ones are the fastest,” he said.

Kevin Reilly, the president of Atlas Sports Genetics and a former weight-lifting coach, expected the test to be controversial. He said some people were concerned that it would cause “a rebirth of eugenics, similar to what Hitler did in trying to create this race of perfect athletes.”

Mr. Reilly said he feared what he called misuse by parents who go overboard with the results and specialize their children too quickly and fervently.

“I’m nervous about people who get back results that don’t match their expectations,” he said. “What will they do if their son would not be good at football? How will they mentally and emotionally deal with that?”

Mr. Reilly insisted that the test is one tool of many that can help children realize their athletic potential. It may even keep an overzealous father from pushing his son to be a quarterback if his genes indicate otherwise, Mr. Reilly said.

If ACTN3 suggests a child may be a great athlete, he said, parents should take a step back and nurture that potential Olympian or N.F.L. star with careful nutrition, coaching and planning. He also said they should hold off on placing a child in a competitive environment until about the age of 8 to avoid burnout.

“Based on the test of a 5-year-old or a newborn, you are not going to see if you have the next Michael Johnson; that’s just not going to happen,” Mr. Reilly said. “But if you wait until high school or college to find out if you have a good athlete on your hands, by then it will be too late. We need to identify these kids from 1 and up, so we can give the parents some guidelines on where to go from there.”

Boyd Epley, a former strength and conditioning coach at the University of Nebraska, said the next step would be a physical test he devised. Atlas plans to direct children to Epic Athletic Performance, a talent identification company that uses Mr. Epley’s index. He founded the company; Mr. Reilly is its president.

China and Russia, Mr. Epley said, identify talent in the very young and whittle the pool of athletes until only the best remain for the national teams.

“This is how we could stay competitive with the rest of the world,” Mr. Epley said of genetic and physical testing. “It could, at the very least, provide you with realistic goals for you and your children.”

The ACTN3 test has been available through the Australian company Genetic Technologies since 2004. The company has marketed the test in Australia, Europe and Japan, but is now entering the United States through Atlas. The testing kit was scheduled to be available starting Monday through the Web site atlasgene.com.

The analysis takes two to three weeks, and the results arrive in the form of a certificate announcing Your Genetic Advantage, whether it is in sprint, power and strength sports; endurance sports; or activity sports (for those with one copy of each variant, and perhaps a combination of strengths). A packet of educational information suggests sports that are most appropriate and what paths to follow so the child reaches his or her potential.

“I find it worrisome because I don’t think parents will be very clear-minded about this,” said William Morgan, an expert on the philosophy of ethics and sport and author of “Why Sports Morally Matter.” “This just contributes to the madness about sports because there are some parents who will just go nuts over the results.

“The problem here is that the kids are not old enough to make rational autonomous decisions about their own life,” he said.

Some parents will steer clear of the test for that reason.

Dr. Ray Howe, a general practitioner in Denver, said he would rather see his 2-year-old, Joseph, find his own way in life and discover what sports he likes the best. Dr. Howe, a former professional cyclist, likened ACTN3 testing to gene testing for breast cancer or other diseases.

“You might be able to find those things out, but do you really want to know?” he said.

Others, like Lori Lacy, 36, said genetic testing would be inevitable. Ms. Lacy, who lives in Broomfield, Colo., has three children ranging in age from 2 months to 5 years.

“Parents will start to say, ‘I know one mom who’s doing the test on her son, so maybe we should do the test too,’ ” she said.

“Peer pressure and curiosity would send people over the edge. What if my son could be a pro football player and I don’t know it?”
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About Jorge Costales

- Cuban Exile [veni] - Raised in Miami [vidi] - American Citizen [vici]
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