Rett protein MeCP2 needed for proper adult neuron function
June 2, 2011 in NeuroscienceThe protein MeCP2 is porridge to the finicky neuron. Like Goldilocks, the neuron or brain cell needs the protein in just the right amount. Girls born with dysfunctional MeCP2 (methyl-CpG-binding protein 2) develop Rett syndrome, a neurological disorder. Too much MeCP2 can cause spasticity or developmental delay with autism-like symptoms in boys.
Now, researchers at Baylor College of Medicine and Texas Children's Hospital have found that the neuron needs a steady supply of this protein for its entire existence. A report on this research appears online in Science Express.
MeCP2 was found in 1999 in the laboratory of Dr. Huda Zoghbi, director of the Jan and Dan Duncan Neurological Research Institute at TCH and professor of neurology, neuroscience, pediatrics and molecular and human genetics at BCM and a Howard Hughes Medical Institute Investigator. A mutation in MeCP2 results in Rett syndrome, a neurological disorder that strikes mainly girls. Male fetuses born with the mutation (which results in dysfunctional protein) die before birth, but girls appear normal until they are between 6 and 18 months. Then they begin to regress and their growth slows. They develop abnormal hand motions such as wringing. Their crawling and walking regresses and they eventually lose the ability to speak or communicate. They exhibit some symptoms of autism.
Clearly, MeCP2 is critical to normal mental functioning, but a question remained. Do neurons need MeCP2 throughout life or would they be protected and work properly if MeCP2 is provided only early in life and then discontinued during adulthood?
To the surprise of Zoghbi and M.D./Ph.D. student Christopher McGraw, the paper's first author, the neurons need the protein throughout life.
"To continue the porridge analogy, taking it away puts you in the same position as someone who never had it," said McGraw.
To demonstrate this, they developed a mouse from which they could eliminate MeCP2 in adulthood.
"We found that they appeared just like the mice born without the protein," said McGraw. The mice developed the Rett-like behaviors, including the limb "clasping" behavior and impaired learning and memory. The mice also died prematurely, 13 weeks after the protein was deleted. Mice born lacking the protein die at about 13 weeks of age as well.
"What this suggests is that the function of this protein is always needed," said McGraw. "Having this protein up to adulthood does not result in the construction of a nervous system that is any more resilient to the loss of MeCP2 than one born without it."
"That was the most surprising to us," said Zoghbi. "The upside of this is if you can add the protein back, you can rescue the neurons, which is indeed what happened when the lab of Dr. Adrian Bird, researcher with the Wellcome Trust Center for Cell Biology, added the gene back in adults in past research," she said. "The new study shows there are no developmental abnormalities. It is all about needing the protein right there to tell the neurons what to do."
MeCP2 affects the epigenetic program of the cell, changing the expression levels of certain genes without changing the sequence of the DNA itself. Scientists are still trying to determine exactly what it does in the cell, and that may enable physicians to develop a treatment that patients would take throughout their lives.
"If we can figure a way to provide the functions of this protein we have a chance to treat these patients successfully and maintain their health," she said.
Just giving patients MeCP2 would not work because of the need to fine-tune the amount of protein in the cell.
She and colleagues are looking instead for drugs that can serve the same function as MeCP2 or that can alter the pathways through which this gene works.
Dr. Rodney C. Samaco of BCM also participated in this research.
More information: http://www.science … early/recent
Provided by
Baylor College of Medicine
-
Mapping the neuron-behavior link in Rett Syndrome
Sep 24, 2008 |
not rated yet |
0
-
Inhibitory neurons key to understanding neuropsychiatric disorders
Nov 10, 2010 |
not rated yet |
0
-
How Rett Syndrome mutation targets the brain
Oct 18, 2006 |
not rated yet |
0
-
Preclinical inquiry into 1 mutation sheds light on addiction and a birth defect
Aug 15, 2010 |
not rated yet |
0
-
Study suggests possible treatment for neurological disorder Rett syndrome
Feb 09, 2009 |
not rated yet |
0
-
Limits to growth: Scientists identify key metastasis-enabling enzyme
May 22, 2012 |
5 / 5 (3) |
0
-
Seeing is as seeing does: Spatially-structured retinal input in early development of cortical maps
Apr 26, 2012 |
5 / 5 (4) |
1
-
Dreamless nights: Brain activity during nonrapid eye movement sleep
Apr 09, 2012 |
4.4 / 5 (12) |
0
-
Take your time: Neurobiology sheds light on the superiority of spaced vs. massed learning
Mar 28, 2012 |
4.5 / 5 (21) |
3
-
Your brain on 'shrooms: fMRI elucidates neural correlates of psilocybin psychedelic state
Feb 29, 2012 |
4.9 / 5 (42) |
45
-
A question about drug tolerance
May 23, 2012
-
Poor nutrition leading to overeating?
May 23, 2012
-
Math and dyslexia?
May 21, 2012
-
portable metabolism meter?
May 21, 2012
-
Rare medical conditions on 20/20 tonight
May 18, 2012
-
"Good" Cholesterol in Doubt
May 17, 2012
- More from Physics Forums - Medical Sciences
More news stories
Persistent sensory experience is good for aging brain
Despite a long-held scientific belief that much of the wiring of the brain is fixed by the time of adolescence, a new study shows that changes in sensory experience can cause massive rewiring of the brain, even as one ages. ...
Neuroscience
16 hours ago |
not rated yet |
0
Boundary stops molecule right where it needs to be
A molecule responsible for the proper formation of a key portion of the nervous system finds its way to the proper place not because it is actively recruited, but instead because it can't go anywhere else.
Neuroscience
16 hours ago |
not rated yet |
0
|
Locating ground zero: How the brain's emergency workers find the disaster area
Like emergency workers rushing to a disaster scene, cells called microglia speed to places where the brain has been injured, to contain the damage by 'eating up' any cellular debris and dead or dying neurons. ...
Neuroscience
16 hours ago |
5 / 5 (2) |
0
|
Genetic 'reset switch' enables signaling pathway to induce multiple developmental outcomes for olfactory neurons
Within the nervous system, a handful of signaling pathways modulate development of a cornucopia of different neuronal subtypes. Even small alterations in neuron differentiation pathways can disrupt subsequent ...
Neuroscience
19 hours ago |
not rated yet |
0
The auditory cortex adapts agilely with concentration
The birth of sensory perception on the human cerebral cortex is yet to be fully explained. The different areas on the cortex function in cooperation, and no perception is the outcome of only one area working alone. In his ...
Neuroscience
20 hours ago |
not rated yet |
0
Amino acid consumption associated with how fast cancer cells divide
For almost a century, researchers have known that cancer cells have peculiar appetites, devouring glucose in ways that normal cells do not. But glucose uptake may tell only part of cancer's metabolic story. Researchers from ...
Like curry? New biological role identified for compound used in ancient medicine
Scientists have just identified a new reason why some curry dishes, made with spices humans have used for thousands of years, might be good for you.
Thioridazine kills cancer stem cells in human while avoiding toxic side-effects of conventional cancer treatments
A team of scientists at McMaster University has discovered a drug, thioridazine, successfully kills cancer stem cells in the human while avoiding the toxic side-effects of conventional cancer treatments.
'Personality genes' may help account for longevity
"It's in their genes" is a common refrain from scientists when asked about factors that allow centenarians to reach age 100 and beyond. Up until now, research has focused on genetic variations that offer a physiological advantage ...
Gene discovery points towards non-hormonal male contraceptive
A new type of male contraceptive could be created thanks to the discovery of a key gene essential for sperm development.
Cyber exercise partners help you go the distance: Motivation gains can double
A new study testing the benefits of a virtual exercise partner shows the presence of a moderately more capable cycling partner can significantly boost the motivation by as much as 100 percent ...