New clues about how amyotrophic lateral sclerosis (ALS) develops

Role of cells other than motor neurons much larger than anticipated

Johns Hopkins scientists say they have evidence from animal studies that a type of central nervous system cell other than motor neurons plays a fundamental role in the development of amyotrophic lateral sclerosis (ALS), a fatal degenerative disease. The discovery holds promise, they say, for identifying new targets for interrupting the disease’s progress.

In a study described online in Nature Neuroscience, the researchers found that, in mice bred with a gene mutation that causes human ALS, dramatic changes occurred in oligodendrocytes—cells that create insulation for the nerves of the central nervous system—long before the first physical symptoms of the disease appeared. Oligodendrocytes located near motor neurons—cells that govern movement—died off at very high rates, and new ones regenerated in their place were inferior and unhealthy.

The researchers also found, to their surprise, that suppressing an ALS-causing gene in oligodendrocytes of mice bred with the disease—while still allowing the gene to remain in the motor neurons—profoundly delayed the onset of ALS. It also prolonged survival of these mice by more than three months, a long time in the life span of a mouse. These observations suggest that oligodendrocytes play a very significant role in the early stage of the disease.

“The abnormalities in oligodendrocytes appear to be having a negative impact on the survival of motor neurons,” says Dwight E. Bergles, Ph.D., a co-author and a professor of neuroscience at the Johns Hopkins University School of Medicine. “The motor neurons seem to be dependent on healthy oligodendrocytes for survival, something we didn’t appreciate before.”

“These findings teach us that cells we never thought had a role in ALS not only are involved but also clearly contribute to the onset of the disease,” says co-author Jeffrey D. Rothstein, M.D., Ph.D., a professor of neurology at Johns Hopkins and director of the Johns Hopkins Medicine Brain Science Institute.

Scientists have long believed that oligodendrocytes functioned only as structural elements of the central nervous system. They wrap around nerves, making up the myelin sheath that provides the “insulation” that allows nerve signals to be transmitted rapidly and efficiently. However, Rothstein and others recently discovered that oligodendrocytes also deliver essential nutrients to neurons, and that most neurons need this support to survive.

The Johns Hopkins team of Bergles and Rothstein published a paper in 2010 that described in mice with ALS an unexpected massive proliferation of oligodendrocyte progenitor cells in the spinal cord’s motor neurons, and that these progenitors were being mobilized to make new oligodendrocytes. The researchers believed that these cells were multiplying because of an injury to oligodendrocytes, but they weren’t sure what was happening. Using a genetic method of tracking the fate of oligodendrocytes, in the new study, the researchers found that cells present in young mice with ALS were dying off at an increasing rate in concert with advancing disease. Moreover, the development of the newly formed oligodendrocytes was stalled and they were not able to provide motor neurons with a needed source of cell nutrients.

To determine whether the changes to the oligodendrocytes were just a side effect of the death of motor neurons, the scientists used a poison to kill motor neurons in the ALS mice and found no response from the progenitors, suggesting, says Rothstein, that it is the mutant ALS gene that is damaging oligodendrocytes directly.

Meanwhile, in separate experiments, the researchers found similar changes in samples of tissues from the brains of 35 people who died of ALS. Rothstein says it may be possible to see those changes early on in the disease and use MRI technology to follow progression.

“If our research is confirmed, perhaps we can start looking at ALS patients in a different way, looking for damage to oligodendrocytes as a marker for disease progression,” Rothstein says. “This could not only lead to new treatment targets but also help us to monitor whether the treatments we offer are actually working.”

ALS, also known as Lou Gehrig’s disease, named for the Yankee baseball great who died from it, affects nerve cells in the brain and spinal cord that control voluntary muscle movement. The nerve cells waste away or die, and can no longer send messages to muscles, eventually leading to muscle weakening, twitching and an inability to move the arms, legs and body. Onset is typically around age 50 and death often occurs within three to five years of diagnosis. Some 10 percent of cases are hereditary.

There is no cure for ALS and there is only one FDA-approved drug treatment, which has just a small effect in slowing disease progression and increasing survival. 

Even though myelin loss has not previously been thought to occur in the gray matter, a region in the brain where neurons process information, the researchers in the new study found in ALS patients a significant loss of myelin in one of every three samples of human tissue taken from the brain’s gray matter, suggesting that the oligodendrocytes were abnormal. It isn’t clear if the oligodendrocytes that form this myelin in the gray matter play a different role than in white matter—the region in the brain where signals are relayed.

The findings further suggest that clues to the treatment of other diseases long believed to be focused in the brain’s gray matter—such as Alzheimer’s disease, Huntington’s disease and Parkinson’s disease—may be informed by studies of diseases of the white matter, such as multiple sclerosis (MS). Bergles says ALS and MS researchers never really thought their diseases had much in common before.

Oligodendrocytes have been under intense scrutiny in MS, Bergles says. In MS, the disease over time can transform from a remitting-relapsing form—in which myelin is attacked but then is regenerated when existing progenitors create new oligodendrocytes to re-form myelin—to a more chronic stage in which oligodendrocytes are no longer regenerated. MS researchers are working to identify new ways to induce the creation of new oligodendrocytes and improve their survival. “It’s possible that we may be able to dovetail with some of the same therapeutics to slow the progression of ALS,” Bergles says.

Renowned scientist Stephen Hawking suffers from amyotrophic lateral sclerosis (ALS). 

(Source: neuromorphogenesis)

Arthur C. Clarke, Stephen Hawking and Carl Sagan.

Drugs Psychedelics & Cannabis

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skeptv:

Hawking: We Need to Leave Earth

Renowned scientist Stephen Hawking says we have 1000 years left on Earth before all the planet’s resources will be used up. Laci looks at the problems we’ll face and Hawking’s solution to saving humanity.

via DNews Channel.

Big Bang Didn’t Need God, Stephen Hawking Says

Our universe didn’t need any divine help to burst into being, famed cosmologist Stephen Hawking told a packed house here at the California Institute of Technology Tuesday night (April 16).

Many people had begun queuing up for free tickets to Hawking’s 8:00 p.m lecture, titled “The Origin of the Universe,” 12 hours earlier. By 6:00 p.m. local time, the line was about a quarter-mile long.

A second auditorium and a Jumbotron-equipped lawn, which itself was jammed with an estimated 1,000 viewers, were needed to handle the overflow crowd. At least one person was observed offering $1,000 for a ticket, with no success.

Stephen Hawking began the event by reciting an African creation myth, and rapidly moved on to big questions such as, Why are we here?

He noted that many people still seek a divine solution to counter the theories of curious physicists, and at one point, he quipped, “What was God doing before the divine creation? Was he preparing hell for people who asked such questions?”

After outlining the historical theological debate about how the universe was created, Hawking gave a quick review of more scientific cosmological explanations, including Fred Hoyle and Thomas Gold’s steady-state theory. This idea hypothesizes that there is no beginning and no end and that galaxies continue to form from spontaneously created matter.

Hawking said this theory and several other ideas don’t hold up, citing recent observations by space telescopes and other instruments.

After giving a brief historical background on relativistic physics and cosmology, Hawking discussed the idea of a repeating Big Bang. He noted that in the 1980s, he and physicist Roger Penrose proved the universe could not “bounce” when it contracted, as had been theorized.

Therefore, time began at the moment of singularity, and this has likely occurred only once, Hawking said. The age of the universe — now believed to be about 13.8 billion years — fits that model, as the number and maturity of observed galaxies seem to fit in the general scheme.

In another observation of modern religion, Hawking noted that in the 1980s, around the time he released a paper discussing the moment the universe was born, Pope John Paul II admonished the scientific establishment against studying the moment of creation, as it was holy.

“I was glad not to be thrown into an inquisition,” Hawking joked.

He closed by outlining “M-theory,” which is based partly on ideas put forward years ago by another famed physicist, Caltech’s Richard Feynman. Hawking sees that theory as the only big idea that really explains what he has observed.

M-theory posits that multiple universes are created out of nothing, Hawking explained, with many possible histories and many possible states of existence. In only a few of these states would life be possible, and in fewer still could something like humanity exist. Hawking mentioned that he felt fortunate to be living in this state of existence.

Hawking closed the event with a familiar plea for continued exploration of the cosmos: “We must continue to go into space for the future of humanity,” he said, adding, “I don’t think we will survive another thousand years without escaping our fragile planet.”

Hawking has been battling the debilitating neurological disorder amyotrophic lateral sclerosis, also known as Lou Gehrig’s disase, for 50 years.

The physicist has been spending a month or so at Caltech, as he does each year, sequestered with colleagues, such as fellow theoretical physicist Kip Thorne, to discuss many great mysteries of the cosmos.

Stay Curious! View The History & Structure of the Universe (Infographic)

This…..this is a quite a treat. Sit back and lose yourself in the version of Symphony of Science’s “A Glorious Dawn” as a planetarium production. Light & burn ‘em if you got ‘em. Ad astra*

via Ott Planetarium

godlessmen:

Stephen Hawking

“Hawking” is the extraordinary story of the planet’s most famous living scientist, told for the first time in his own words and by those closest to him. Made with unique access to Hawking’s private life, this is an intimate and moving journey into Stephen’s world, both past and present. An inspirational portrait of an iconic figure, Hawking relates his incredible personal journey from boyhood under-achiever, to PhD genius, to being diagnosed with Motor Neuron Disease and given just two years to live. Despite the constant threat of death, Hawking manages to make many remarkable scientific discoveries and rises to fame and super-stardom. “Hawking” - a remarkable man, and a remarkable movie.

Everyone please stay on top of this and update this post on the release date and any links you find available in order to share this with everyone. It’s about time they do Mr. Hawking a great service by publicizing this biopic of his life and achievements for the world to see.

electricspacekoolaid:

Hawking: A Stephen Hawking Biopic

Hawking will tell the dramatic story of the planet’s most famous living scientist, told for the first time in his own words and by those closest to him. Made with unique access to Hawking’s private life, this is an intimate and moving look into Stephen Hawking’s world, both past and present. The biopic charts his his incredible personal journey from boyhood underachiever, to scientific genius and multi-million selling author & how he overcame being diagnosed with Motor Neurone disease – and being given just two years to live – to make amazing scientific discoveries and become an icon of triumph over adversity. Stephen Hawking’s sister Mary, his ex-wife Jane, Roger Penrose, Buzz Aldrin, Benedict Cumberbatch, Jim Carey and Sir Richard Branson will all be interviewed for the production.

nappyhappy:

‘Allegiance to Science’ Brooches have arrived at Daisy’s Creations! 

electricspacekoolaid:

“Intelligence is the ability to adapt” - Stephen Hawking

atomstargazer:

Stephen Hawking at a glance

He’s made some of the most notable scientific contributions of our time and dedicated his life to discovering how the universe works, and he’s been confined to a wheelchair for over 40 years. But before Stephen Hawking made himself into a legend, he came from humble beginnings.

Stephen Hawking (via ikenbot)

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