Study offers insights into role of muscle weakness in Down syndrome
It is well known that people with Down syndrome (DS) suffer from marked muscle weakness. Even the simple tasks of independent living, such as getting out of a chair or climbing a flight of stairs, can become major obstacles. This can reduce the quality of life for those with DS and lead to a loss of independence. Now, a new study sheds light on some of the suspected causes of muscle weakness.
Led by scientists from Syracuse University, a research team has investigated muscle weakness in a mouse model of DS. "If we understand the cause of this muscle weakness, we can begin to look at potential therapies for treating it," said Patrick M. Cowley, lead researcher.
The investigators analyzed the soleus muscle—a muscle in the lower leg—and looked into whether the weakness was due to a deficiency of the muscle itself, independent of its activation by the nervous system.
"Surprisingly, we found that the strength of the muscle itself was the same between the DS and control mice—suggesting that factors in the nervous system may play a more dominant role in explaining muscle weakness in DS," said Cowley.
The article is entitled "Functional and Biochemical Characterization of the Soleus Muscle in Down Syndrome Mice: Insight into the Muscle Dysfunction Seen in the Human Condition," (http://bit.ly/TXsmby) It appears in the online edition of the American Journal of Physiology – Regulatory, Integrative and Comparative Physiology published by the American Physiological Society (APS).
The researchers removed soleus muscles from 14 DS mice and 16 controls. They tested the muscles for strength, fatigue and recovery. They also assessed the distribution of fiber types in muscles from both groups.
Because there are three copies instead of two of chromosome 21 in persons with DS, the researchers looked at whether the additional genes caused over-expression of proteins that could then lead to oxidative stress. They also looked for well-known markers of oxidative injury.
A cell-level deficiency in processing of oxygen might also explain the muscle weakness. To determine if this was the case, the researchers tested for the level of two markers for oxidative capacity in the mitochondria, where oxygen metabolism takes place in cells.
Finally, the researchers used microarray analysis to investigate the gene expression and molecular pathways in the muscles of DS mice.
There were no significant differences in the force production of the muscles between the two groups. This finding means that muscle weakness in DS was not due to inherent differences in muscle force generating capacity. Fatigability of the muscle from DS mice was not different from the controls. It did, however, show impaired recovery. There were no significant differences in muscle fiber types between the groups.
While one marker of the cells' ability to process oxygen was lower in DS mice, the other was similar in both groups, meaning that there was not a clear indication of mitochondrial limitation that could explain muscle weakness in DS.
Finally, the researchers found that SOD1, an important antioxidant, was overexpressed in DS mice. This was not a surprise because the gene for SOD1 is tripled in DS. However, there was no increase in markers of oxidative injury, suggesting that this over-expression did not led to oxidative stress in DS muscle.
There were numerous altered pathways in DS muscle revealed by microarray analysis including the breakdown of proteins, metabolism of glucose and fat, and neuromuscular transmission.
Importance of the Findings
This study shows the importance of better understanding muscle weakness in DS. Interestingly, the study found that the weakness was not due to a deficiency in the muscle itself. This may indicate that neural activation of the muscle plays a greater role in explaining weakness in persons with DS. "We now know that the muscle is not the major issue responsible for muscle weakness in DS mice," explained Cowley. "We need to look at the neural factors involved—from the motor systems in the brain to the neuromuscular junction—to determine the cause of muscular weakness in people with Down syndrome."
Provided by American Physiological Society
- Multifactorial mechanisms underlie leg weakness in hip OA Aug 09, 2012 | not rated yet | 0
- Muscle weakness: New mutation identified Jun 14, 2007 | not rated yet | 0
- Unraveling why children with Down syndrome have increased leukemia risk Feb 22, 2012 | not rated yet | 0
- At the right place at the right time—new insights into muscle stem cells Sep 17, 2012 | not rated yet | 0
- Weakness in aging tied to leaky muscles Aug 02, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
Ernie Pyle – an iconic war correspondent in World War II – reportedly said "There are no atheists in foxholes." A new joint study between two brothers at Cornell and Virginia Wesleyan found that only ...
Psychology & Psychiatry 2 hours ago | 2.5 / 5 (2) | 0
(Medical Xpress)—Research by Stanford scholar Emma Seppala at the Center for Compassion and Altruism Research and Education found that post-traumatic stress disorder decreased in veterans who participated ...
Psychology & Psychiatry 2 hours ago | not rated yet | 0
(Medical Xpress)—Patients with diabetes who are depressed are much more likely to develop episodes of dangerously low blood sugars, or hypoglycemia, than are those who are not depressed, a new study has ...
Psychology & Psychiatry 3 hours ago | not rated yet | 0 |
A brief visual task can predict IQ, according to a new study. This surprisingly simple exercise measures the brain's unconscious ability to filter out visual movement. The study shows that individuals whose ...
Psychology & Psychiatry 23 hours ago | 4.5 / 5 (11) | 2 |
Nervous about that upcoming job interview? You might want to take steps to reduce your jitters, especially if you are a man.
Psychology & Psychiatry May 23, 2013 | 5 / 5 (1) | 0
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
55 seconds ago | not rated yet | 0 |
Young children who missed more than half of recommended well-child visits had up to twice the risk of hospitalization compared to children who attended most of their visits, according to a study published today in the American Jo ...
16 seconds ago | not rated yet | 0
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
2 hours ago | 5 / 5 (3) | 0 |
(Medical Xpress)—Regulating the distribution of power in neurons is done by a system that makes the national electric grid look simple by comparison. Each neuron has several thousand mitochondria confined ...
18 hours ago | 4.9 / 5 (8) | 0 |
New research presented today shows that formation of new neurons in the hippocampus - a brain region known for its importance in learning and remembering - could cause forgetting of old memories by causing a reorganization ...
2 hours ago | 5 / 5 (1) | 0