2 replies to this topic

[Strangelove]

English is not my native language, but I am going to put this the best way so it seems understanable that maybe a different way to use novel substances to boost brain power, than trying to supplement and "push" the brain for increased energy or neural growth. I am not sure if something similar has been discussed before, but I would appreciate any input even speculative on the nature of regular short-term mental exsaustion and how this may affect maximum brain development in the long-term.

This is my first post, I cannot add links, so I would copy/paste two articles and a part from wikipedia for the quite interesting for me Myostatin.

1. Does Thinking Really Hard Burn More Calories? An online article from scientific American. It gives current research that glucose depletion does not seem to be a major issue with mental exsaustion. Especially telling (at least for my thinking) is the last paragraph in the end of the article.

"My general hypothesis is that the brain is a lazy bum," he says. "The brain has a hard time staying focused on just one thing for too long. It's possible that sustained concentration creates some changes in the brain that promote avoidance of that state. It could be like a timer that says, 'Okay you're done now.' Maybe the brain just doesn't like to work so hard for so long."

Myostatin, and why everyone could possibly have the body of a bodybuilding champion.

I have read a bit about myostatin and its effects on body composition and is interesting from an evolutionary point of view, I was wondering if something similar applies on "brain composition", that is a natural brake in brain's possibly maximum development.

A paragraph from wikipedia follows

Clinical research
Further research into myostatin and the myostatin gene may lead to therapies for muscular dystrophy.^[21][22] The idea is to introduce substances that block myostatin. A monoclonal antibody specific to myostatin increases muscle mass in mice.^[23] Similar results in monkeys were obtained.^[5]
A two-week treatment of normal mice with soluble activin type IIB receptor, a molecule that is normally attached to cells and binds to myostatin, leads to a significantly increased muscle mass (up to 60%).^[24] It is thought that binding of myostatin to the soluble activin receptor prevents it from interacting with the cell-bound receptors.
It remains unclear as to whether long-term treatment of muscular dystrophy with myostatin inhibitors is beneficial, as the depletion of muscle stem cells could worsen the disease later on. As of 2012^[update], no myostatin-inhibiting drugs for humans are on the market, but an antibody genetically engineered to neutralize myostatin was developed by New Jersey pharmaceutical company Wyeth.^[25] The inhibitor is called MYO-029, but, after an initial clinical trial, Wyeth says they will not be developing the drug.^[26] Some athletes, eager to get their hands on such drugs, turn to the internet, where fake "myostatin blockers" are being sold.^[5]
Myostatin levels are effectively decreased by creatine supplementation.^{[27][not in citation given]}
A technique for detecting mutations in myostatin variants has been developed.

Myostatin seems to be an "evolutionary brake", in developing too much mass for the organism to sustain through food intake. I was wondering if there is a similar mechanism that put "brakes" on short-term brain endurance and most importantly for the long term maximum possible brain development. Searching online I found the article below that is close to the logic here.

Boston, MA-Scientists at Schepens Eye Research Institute have identified specific molecules in the brain that are responsible for awakening and putting to sleep brain stem cells, which, when activated, can transform into neurons (nerve cells) and repair damaged brain tissue. Their findings are published online this week in the Proceedings of the National Academy of Science (PNAS).

A previous paper by the same group found stem cells in many more parts of the brain than stem cells were previously know to exist. This suggests more parts of the brain are repairable via mechanisms already there if we can only find ways to get control of those mechanisms.

An earlier paper (published in the May issue of Stem Cells) by the same scientists laid the foundation for the PNAS study findings by demonstrating that neural stem cells exist in every part of the brain, but are mostly kept silent by chemical signals from support cells known as astrocytes.
"The findings from both papers should have a far-reaching impact," says principal investigator, Dr. Dong Feng Chen, who is an associate scientist at Schepens Eye Research Institute and an assistant professor of ophthalmology at Harvard Medical School. Chen believes that tapping the brain¹s dormant, but intrinsic, ability to regenerate itself is the best hope for people suffering from brain-ravaging diseases such as Parkinson¹s or Alzheimer¹s disease or traumatic brain or spinal cord injuries.
Until these studies, which were conducted in the adult brains of mice, scientists assumed that only two parts of the brain contained neural stem cells and could turn them on to regenerate brain tissue-- the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). The hippocampus is responsible for learning and memory, while the SVZ is a brain structure situated throughout the walls of lateral ventricles (part of the ventricular system in the brain) and is responsible for generating neurons reponsible for smell. So scientists believed that when neurons died in other areas of the brain, they were lost forever along with their functions.

Molecules named ephrin-A2 and ephrin-A3 inhibit neural stem cell growth. So inhibitors of those molecules might help to activate stem cells for brain repair. Sonic hedgehog (which the press release below misspells as sonic hedghoc) stimulates neural stem cell growth. Inhibit the ephrins and stimulate sonic hedgehog and the result would be much more neural stem cell growth.

In the second (PNAS) study, the team went on to discover the exact nature of those different chemical signals. They learned that in the areas where stem cells were sleeping, astrocytes were producing high levels of two related molecules--ephrin-A2 and ephrin-A3. They also found that removing these molecules (with a genetic tool) activated the sleeping stem cells.
The team also found that astrocytes in the hippocampus produce not only much lower levels of ephrin-A2 and ephrin-A3, but also release a protein named sonic hedghoc that, when added in culture or injected into the brain, stimulates neural stem cells to divide and become new neurons.

What I'd like to know: As the brain ages do the astrocyte support cells excrete more ephrin-A2 and ephrin-A3 and less sonic hedgehog? Maybe the aging brain becomes less able to do repair because evolutionary natural selection selected for stem cell inhibition as an anti-cancer strategy. Therapies to activate brain stem cells might increase risk of brain tumors. Of course, if you have Parkinson's Disease your trade-off might weigh to taking that risk as likely to deliver the best net benefit.
The eventual development of techniques to create youthful neural stem cells will provide stem cells that can be safely stimulate to grow without running a cancer risk. But How to replace the old stem cells with young ones? It is not enough to add the newer younger stem cells to the brain (and just getting the new stem cells into all the spots in the brain they need to go is a challenge). We need to get rid of the old stem cells so that a drug that boosts stem cell growth will only stimulate the new stem cells and not the old stem cells too.
I wrote a post back in November 2004 about the ability of sonic hedgehog to triple brain stem cell growth. The use of sonic hedgehog for this purpose is well known among the researchers in this area.



^{The point I am trying to make is that by inhibiting chemicals in the brain that make us "mentally lazy" and stop neural growth, and by taking the time to work even more intensely in our interests, we could train our brain much more efficiently, having long term advantages in brain boosting effects and better mastery in our fields or hobbies.}

[Strangelove]

I definitely need some of the substances mentioned in the article above, after hours of reading, definite brain fog and tired eyes, the title of this post should be "Myostatin inhibitors for the brain".

Here is the quite interesting full article from scientific American.

Does Thinking Really Hard Burn More Calories?
Unlike physical exercise, mental workouts probably do not demand significantly more energy than usual. Believing we have drained our brains, however, may be enough to induce weariness
By Ferris Jabr


Between October and June they shuffle out of auditoriums, gymnasiums and classrooms, their eyes adjusting to the sunlight as their fingers fumble to awaken cell phones that have been silent for four consecutive hours. Some raise a hand to their foreheads, as though trying to rub away a headache. Others linger in front of the parking lot, unsure of what to do next. They are absolutely exhausted, but not because of any strenuous physical activity. Rather, these high school students have just taken the SAT. "I was fast asleep as soon as I got home," Ikra Ahmad told The Local, a New York Times blog, when she was interviewed for a story on "SAT hangover."

Temporary mental exhaustion is a genuine and common phenomenon, which, it is important to note, differs from chronic mental fatigue associated with regular sleep deprivation and some medical disorders. Everyday mental weariness makes sense, intuitively. Surely complex thought and intense concentration require more energy than routine mental processes. Just as vigorous exercise tires our bodies, intellectual exertion should drain the brain. What the latest science reveals, however, is that the popular notion of mental exhaustion is too simplistic. The brain continuously slurps up huge amounts of energy for an organ of its size, regardless of whether we are tackling integral calculus or clicking through the week's top 10 LOLcats. Although firing neurons summon extra blood, oxygen and glucose, any local increases in energy consumption are tiny compared with the brain's gluttonous baseline intake. So, in most cases, short periods of additional mental effort require a little more brainpower than usual, but not much more. Most laboratory experiments, however, have not subjected volunteers to several hours' worth of challenging mental acrobatics. And something must explain the feeling of mental exhaustion, even if its physiology differs from physical fatigue. Simply believing that our brains have expended a lot of effort might be enough to make us lethargic.

Brainpower
Although the average adult human brain weighs about 1.4 kilograms, only 2 percent of total body weight, it demands 20 percent of our resting metabolic rate (RMR)—the total amount of energy our bodies expend in one very lazy day of no activity. RMR varies from person to person depending on age, gender, size and health. If we assume an average resting metabolic rate of 1,300 calories, then the brain consumes 260 of those calories just to keep things in order. That's 10.8 calories every hour or 0.18 calories each minute. (For comparison's sake, see Harvard's table of calories burned during different activities). With a little math, we can convert that number into a measure of power:

—Resting metabolic rate: 1300 kilocalories, or kcal, the kind used in nutrition
—1,300 kcal over 24 hours = 54.16 kcal per hour = 15.04 gram calories per second
—15.04 gram calories/sec = 62.93 joules/sec = about 63 watts
—20 percent of 63 watts = 12.6 watts

So a typical adult human brain runs on around 12 watts—a fifth of the power required by a standard 60 watt lightbulb. Compared with most other organs, the brain is greedy; pitted against man-made electronics, it is astoundingly efficient. IBM's Watson, the supercomputer that defeated Jeopardy! champions, depends on ninety IBM Power 750 servers, each of which requires around one thousand watts.

Energy travels to the brain via blood vessels in the form of glucose, which is transported across the blood-brain barrier and used to produce adenosine triphosphate (ATP), the main currency of chemical energy within cells. Experiments with both animals and people have confirmed that when neurons in a particular brain region fire, local capillaries dilate to deliver more blood than usual, along with extra glucose and oxygen. This consistent response makes neuroimaging studies possible: functional magnetic resonance imaging (fMRI) depends on the unique magnetic properties of blood flowing to and from firing neurons. Research has also confirmed that once dilated blood vessels deliver extra glucose, brain cells lap it up.

Extending the logic of such findings, some scientists have proposed the following: if firing neurons require extra glucose, then especially challenging mental tasks should decrease glucose levels in the blood and, likewise, eating foods rich in sugars should improve performance on such tasks. Although quite a few studies have confirmed these predictions, the evidence as a whole is mixed and most of the changes in glucose levels range from the miniscule to the small. In a study at Northumbria University, for example, volunteers that completed a series of verbal and numerical tasks showed a larger drop in blood glucose than people who just pressed a key repeatedly. In the same study, a sugary drink improved performance on one of the tasks, but not the others. At Liverpool John Moores University volunteers performed two versions of the Stroop task, in which they had to identify the color of ink in which a word was printed, rather than reading the word itself: In one version, the words and colors matched—BLUE appeared in blue ink; in the tricky version, the word BLUE appeared in green or red ink. Volunteers who performed the more challenging task showed bigger dips in blood glucose, which the researchers interpreted as a direct cause of greater mental effort. Some studies have found that when people are not very good at a particular task, they exert more mental effort and use more glucose and that, likewise, the more skilled you are, the more efficient your brain is and the less glucose you need. Complicating matters, at least one study suggests the opposite—that more skillful brains recruit more energy.*

Not so simple sugars
Unsatisfying and contradictory findings from glucose studies underscore that energy consumption in the brain is not a simple matter of greater mental effort sapping more of the body's available energy. Claude Messier of the University of Ottawa has reviewed many such studies. He remains unconvinced that any one cognitive task measurably changes glucose levels in the brain or blood. "In theory, yes, a more difficult mental task requires more energy because there is more neural activity," he says, "but when people do one mental task you won't see a large increase of glucose consumption as a significant percentage of the overall rate. The base level is quite a lot of energy—even in slow-wave sleep with very little activity there is still a high baseline consumption of glucose." Most organs do not require so much energy for basic housekeeping. But the brain must actively maintain appropriate concentrations of charged particles across the membranes of billions of neurons, even when those cells are not firing. Because of this expensive and continuous maintenance, the brain usually has the energy it needs for a little extra work.

Authors of other review papers have reached similar conclusions. Robert Kurzban of the University of Pennsylvania points to studies showing that moderate exercise improves people's ability to focus. In one study, for example, children who walked for 20 minutes on a treadmill performed better on an academic achievement test than children who read quietly before the exam. If mental effort and ability were a simple matter of available glucose, then the children who exercised—and burnt up more energy—should have performed worse than their quiescent peers.

The influence of a mental task's difficulty on energy consumption "appears to be subtle and probably depends on individual variation in effort required, engagement and resources available, which might be related to variables such as age, personality and gluco-regulation," wrote Leigh Gibson of Roehampton University in a review on carbohydrates and mental function.

Both Gibson and Messier conclude that when someone has trouble regulating glucose properly—or has fasted for a long time—a sugary drink or food can improve their subsequent performance on certain kinds of memory tasks. But for most people, the body easily supplies what little extra glucose the brain needs for additional mental effort.

Body and mind
If challenging cognitive tasks consume only a little more fuel than usual, what explains the feeling of mental exhaustion following the SAT or a similarly grueling mental marathon? One answer is that maintaining unbroken focus or navigating demanding intellectual territory for several hours really does burn enough energy to leave one feeling drained, but that researchers have not confirmed this because they have simply not been tough enough on their volunteers. In most experiments, participants perform a single task of moderate difficulty, rarely for more than an hour or two. "Maybe if we push them harder, and get people to do things they are not good at, we would see clearer results," Messier suggests.

Equally important to the duration of mental exertion is one's attitude toward it. Watching a thrilling biopic with a complex narrative excites many different brain regions for a good two hours, yet people typically do not shamble out of the theater complaining of mental fatigue. Some people regularly curl up with densely written novels that others might throw across the room in frustration. Completing a complex crossword or sudoku puzzle on a Sunday morning does not usually ruin one's ability to focus for the rest of the day—in fact, some claim it sharpens their mental state. In short, people routinely enjoy intellectually invigorating activities without suffering mental exhaustion.

Such fatigue seems much more likely to follow sustained mental effort that we do not seek for pleasure—such as the obligatory SAT—especially when we expect that the ordeal will drain our brains. If we think an exam or puzzle will be difficult, it often will be. Studies have shown that something similar happens when people exercise and play sports: a large component of physical exhaustion is in our heads. In related research, volunteers that cycled on an exercise bike following a 90-minute computerized test of sustained attention quit pedaling from exhaustion sooner than participants that watched emotionally neutral documentaries before exercising. Even if the attention test did not consume significantly more energy than watching movies, the volunteers reported feeling less energetic. That feeling was powerful enough to limit their physical performance.

In the specific case of the SAT, something beyond pure mental effort likely contributes to post-exam stupor: stress. After all, the brain does not function in a vacuum. Other organs burn up energy, too. Taking an exam that partially determines where one will spend the next four years is nerve-racking enough to send stress hormones swimming through the blood stream, induce sweating, quicken heart rates and encourage fidgeting and contorted body postures. The SAT and similar trials are not just mentally taxing—they are physically exhausting, too.

A small but revealing study suggests that even mildly stressful intellectual challenges change our emotional states and behaviors, even if they do not profoundly alter brain metabolism. Fourteen female Canadian college students either sat around, summarized a passage of text or completed a series of computerized attention and memory tests for 45 minutes before feasting on a buffet lunch. Students who exercised their brains helped themselves to around 200 more calories than students who relaxed. Their blood glucose levels also fluctuated more than those of students who just sat there, but not in any consistent way. Levels of the stress hormone cortisol, however, were significantly higher in students whose brains were busy, as were their heart rates, blood pressure and self-reported anxiety. In all likelihood, these students did not eat more because their haggard brains desperately needed more fuel; rather, they were stress eating.

Messier has related explanation for everyday mental weariness: "My general hypothesis is that the brain is a lazy bum," he says. "The brain has a hard time staying focused on just one thing for too long. It's possible that sustained concentration creates some changes in the brain that promote avoidance of that state. It could be like a timer that says, 'Okay you're done now.' Maybe the brain just doesn't like to work so hard for so long."

[abelard lindsay]

Well inhibiting the right PDE4 enzyme subtype will cause significant increases in memory. PDE4D5 and PDE4D6 IIRC. There are some research chemicals out there that they've used to make some very intelligent mice.