Basics: Job Description Grows for Our Utility Hormone

Researchers lately have learned that serotonin plays an impressive number of critical roles throughout the body, both below the neck and above it, and from the earliest days of prenatal pre-sentience. One team has found that serotonin starts seeping into the embryonic forebrain during the first trimester of pregnancy, helping to shape the basic neural circuitry that later in life will be applied to learning, emoting and consulting a psychiatrist.

More surprising still, Pat Levitt of the Zilkha Neurogenetic Institute at the University of Southern California and his colleagues reported in the April 21 issue of the journal Nature, the creator of all that architectonic prenatal serotonin turns out to be an organ long dismissed as a passive sieve: the placenta. Other researchers have determined that serotonin in the gut helps orchestrate the remodeling of bone, the lifelong buildup and breakdown of osteoclasts and osteoblasts that make the human skeleton such an exciting organ system to own.

The latest findings may never lead to a satisfying pharmacologic fix for what the psychologist Kay Redfield Jamison has called “ordinary existential angst” and others “terminal you-ness,” but they may someday help stiffen the spine, and they remind us that it’s worth listening to serotonin no matter what it has to say.

“If I didn’t admit to being surprised by the scope of serotonin function, and how important it is to tissues like bone,” said Patricia Ducy, who studies the effect of serotonin on bone biology at Columbia University Medical Center, “I would be lying.”

Serotonin is a tiny molecule, a bibelot built of just 10 carbon atoms, a dozen hydrogens, two nitrogens and a single oxygen. The molecule was first detected in 1948, in blood serum, and it was shown be a vascular toning agent that causes blood vessels to constrict — hence its name, a conjoinment of “serum” and “tone.” Five years later, scientists found serotonin in brain extracts as well, and they soon learned that the recently invented hallucinogenic drug lysergic acid diethylamide worked by tapping into the brain’s serotonin system and that if you took too much LSD you might end up wearing hair garlands and overusing the word “wow.”

Serotonin and serotoninlike molecules have also been found throughout the animal, plant and fungal communities. As a vasoconstrictor, serotonin helps give a wasp sting its zing, and as a powerful hormone serotonin specifies the body plan of a sea urchin developing in its egg.

To synthesize their serotonin, humans and other species must start with tryptophan, an essential amino acid found in many dietary items, including turkey, cheese, tofu, nuts, seeds and bananas, a fruit that, despite its notorious comedic associations, always ends up on lists of “very wholesome foods with possible medicinal value.”

Much effort has been devoted to the study of how serotonin operates in the brain, where it serves as a neurotransmitter, a chemical that activates brain cells to fire messages at each other through their impulsive Morse code. In the adult brain, all serotonin is supplied by a handful of cells located in the hindbrain, atop the spinal cord, but those neurons share their bounty widely through filamentous projections.

Not surprisingly, the serotonin signaling system is wondrously complex. Scientists have identified at least 15 distinct serotonin receptors, proteins that clasp onto serotonin and react accordingly. In addition, there is the serotonin transporter, a janitorial protein that removes the serotonin from the little cleft between nerve cells once the molecule’s transmission task is through.

For all the intricacy, serotonin in the brain has a basic personality. “It’s a molecule involved in helping people cope with adversity, to not lose it, to keep going and try to sort everything out,” said Philip J. Cowen, a serotonin expert at Oxford University and the Medical Research Council. In the fine phrase of his Manchester University colleague Bill Deakin, “it’s the ‘Don’t panic yet’ neurotransmitter,” said Dr. Cowen. Given serotonin’s job description, disturbances in the system can contribute to depression, anxiety, panic attacks and mental calcification, an inability to see the world anew — at least in otherwise vulnerable people.

Dr. Cowen emphasizes that serotonin disruption alone does not directly cause depression. Experiments have shown that if you shut down serotonin production in normal people by subjecting them to an extreme tryptophan-free diet, they may not notice the difference; those with a history of depression, however, may well fall back into their gloom.

Prozac, Zoloft and other so-called serotonin-specific reuptake inhibitors seek to enhance serotonin trafficking by blocking the serotonin transporter, thus allowing the neurotransmitter to linger longer in neuronal vestibules and keep supplying its stimulus package to any shovel-ready receptor that will have it.

This article has been revised to reflect the following correction:

Correction: May 5, 2011

The Basics column on Tuesday, about the many functions of the hormone serotonin, misstated the academic credentials of Kay Redfield Jamison. Though she is a professor of psychiatry at the Johns Hopkins School of Medicine, Dr. Jamison is a psychologist, not a psychiatrist.

 

Basics: Job Description Grows for Our Utility Hormone

Researchers lately have learned that serotonin plays an impressive number of critical roles throughout the body, both below the neck and above it, and from the earliest days of prenatal pre-sentience. One team has found that serotonin starts seeping into the embryonic forebrain during the first trimester of pregnancy, helping to shape the basic neural circuitry that later in life will be applied to learning, emoting and consulting a psychiatrist.

More surprising still, Pat Levitt of the Zilkha Neurogenetic Institute at the University of Southern California and his colleagues reported in the April 21 issue of the journal Nature, the creator of all that architectonic prenatal serotonin turns out to be an organ long dismissed as a passive sieve: the placenta. Other researchers have determined that serotonin in the gut helps orchestrate the remodeling of bone, the lifelong buildup and breakdown of osteoclasts and osteoblasts that make the human skeleton such an exciting organ system to own.

The latest findings may never lead to a satisfying pharmacologic fix for what the psychologist Kay Redfield Jamison has called “ordinary existential angst” and others “terminal you-ness,” but they may someday help stiffen the spine, and they remind us that it’s worth listening to serotonin no matter what it has to say.

“If I didn’t admit to being surprised by the scope of serotonin function, and how important it is to tissues like bone,” said Patricia Ducy, who studies the effect of serotonin on bone biology at Columbia University Medical Center, “I would be lying.”

Serotonin is a tiny molecule, a bibelot built of just 10 carbon atoms, a dozen hydrogens, two nitrogens and a single oxygen. The molecule was first detected in 1948, in blood serum, and it was shown be a vascular toning agent that causes blood vessels to constrict — hence its name, a conjoinment of “serum” and “tone.” Five years later, scientists found serotonin in brain extracts as well, and they soon learned that the recently invented hallucinogenic drug lysergic acid diethylamide worked by tapping into the brain’s serotonin system and that if you took too much LSD you might end up wearing hair garlands and overusing the word “wow.”

Serotonin and serotoninlike molecules have also been found throughout the animal, plant and fungal communities. As a vasoconstrictor, serotonin helps give a wasp sting its zing, and as a powerful hormone serotonin specifies the body plan of a sea urchin developing in its egg.

To synthesize their serotonin, humans and other species must start with tryptophan, an essential amino acid found in many dietary items, including turkey, cheese, tofu, nuts, seeds and bananas, a fruit that, despite its notorious comedic associations, always ends up on lists of “very wholesome foods with possible medicinal value.”

Much effort has been devoted to the study of how serotonin operates in the brain, where it serves as a neurotransmitter, a chemical that activates brain cells to fire messages at each other through their impulsive Morse code. In the adult brain, all serotonin is supplied by a handful of cells located in the hindbrain, atop the spinal cord, but those neurons share their bounty widely through filamentous projections.

Not surprisingly, the serotonin signaling system is wondrously complex. Scientists have identified at least 15 distinct serotonin receptors, proteins that clasp onto serotonin and react accordingly. In addition, there is the serotonin transporter, a janitorial protein that removes the serotonin from the little cleft between nerve cells once the molecule’s transmission task is through.

For all the intricacy, serotonin in the brain has a basic personality. “It’s a molecule involved in helping people cope with adversity, to not lose it, to keep going and try to sort everything out,” said Philip J. Cowen, a serotonin expert at Oxford University and the Medical Research Council. In the fine phrase of his Manchester University colleague Bill Deakin, “it’s the ‘Don’t panic yet’ neurotransmitter,” said Dr. Cowen. Given serotonin’s job description, disturbances in the system can contribute to depression, anxiety, panic attacks and mental calcification, an inability to see the world anew — at least in otherwise vulnerable people.

Dr. Cowen emphasizes that serotonin disruption alone does not directly cause depression. Experiments have shown that if you shut down serotonin production in normal people by subjecting them to an extreme tryptophan-free diet, they may not notice the difference; those with a history of depression, however, may well fall back into their gloom.

Prozac, Zoloft and other so-called serotonin-specific reuptake inhibitors seek to enhance serotonin trafficking by blocking the serotonin transporter, thus allowing the neurotransmitter to linger longer in neuronal vestibules and keep supplying its stimulus package to any shovel-ready receptor that will have it.

This article has been revised to reflect the following correction:

Correction: May 5, 2011

The Basics column on Tuesday, about the many functions of the hormone serotonin, misstated the academic credentials of Kay Redfield Jamison. Though she is a professor of psychiatry at the Johns Hopkins School of Medicine, Dr. Jamison is a psychologist, not a psychiatrist.

 

Tokyo Utility Lays Out Plan for Its Reactors

TOKYO — The Tokyo Electric Power Company laid out an ambitious plan on Sunday for bringing the reactors at its hobbled Fukushima Daiichi nuclear power plant into a stable state known as cold shutdown within the next nine months and for trying to reduce the levels of radioactive materials being released in the meantime.

The chairman of Tokyo Electric, Tsunehisa Katsumata, at a news conference on Sunday in Tokyo.

A robot measuring radiation levels at the Fukushima Daiichi plant.

The blueprint for action represents Tokyo Electric’s most concrete timetable yet for controlling the reactors and improving safety at the plant, which was damaged by a massive earthquake and tsunami nearly six weeks ago.

The first part of the plan, expected to take three months, would include building new cooling systems, critical to preventing catastrophic releases of radioactive materials. The company then hopes to cover three badly damaged reactor buildings and install filters to reduce contamination being released into the air.

By announcing the construction of new cooling systems, the company implicitly acknowledged what outside experts had been warning for weeks: that the company’s earlier plan to repair the existing system was unlikely to work because the equipment was too badly damaged. The change in approach means that the country must resign itself to several more months of radioactive emissions — into the air and possibly into the Pacific — even though the plant appears to be less volatile than it was.

For weeks, workers have been consumed with reacting to a cascade of problems created not only by the original disasters but also by makeshift fixes for bringing the plant under control. By making its announcement on Sunday, Tokyo Electric was trying to show that conditions had apparently improved enough in recent days that it was now able to turn some of its attention to planning for the future.

“The company has been doing its utmost to prevent a worsening of the situation,” Tokyo Electric’s chairman, Tsunehisa Katsumata, told a news conference.

“We have put together a road map,” he said, adding, “We will put our full efforts into achieving these goals.”

On Sunday, meanwhile, the government said that evacuees who were forced to leave their homes near the Daiichi plant will be able to start returning in six to nine months, after the land is decontaminated. The announcement seemed to suggest that few places would be put off limits, as they were after the more devastating 1986 Chernobyl disaster in Ukraine. But Japanese officials did not provide specifics about how contaminated the land was within several miles of the plant.

In any case, the statements were the clearest indication yet that the tens of thousands of people evacuated from the area and living in shelters will not soon be able to return to their homes, or to towns that were destroyed by the tsunami. It also means that the badly shaken government will have to continue to provide for the displaced people even as it struggles to rebuild from the quake and stabilize the economy.

One government official and a nuclear power expert said they thought Tokyo Electric’s plan could work, although one said the company should try for a cold shutdown sooner. A cold shutdown means that the temperature of the?water in a reactor?is below the boiling point. Although cooling must continue, the water will not boil away quickly, even at atmospheric pressure.? Boiling must be avoided because fuel rods have to be kept under water to avoid meltdown.

The Japanese government and the company, known as Tepco, have been overly optimistic in the past. Several weeks ago, for instance, the company said it hoped that its success in bringing live power lines back to the plant would enable workers to quickly restart the existing cooling systems even though the equipment would have had to survive not just the natural disasters, but the explosions that rocked the plant in the following days.

The announcement on Sunday that new cooling systems would be built was the first admission that efforts to restart the old system had failed.

Reporting was contributed by Keith Bradsher, Ken Ijichi, Yasuko Kamiizumi, Andrew Pollack, Kantaro Suzuki and Hiroko Tabuchi from Tokyo, and Matthew L. Wald from Washington.