PRESS-NEWS.org - Press Release Distribution
FREE PRESS RELEASES DISTRIBUTION

Cedars-Sinai study of Lou Gehrig's disease shifts 'origin' focus to brain's motor neurons

Most research aims at spinal motor neurons and nerve-muscle connections, but new study shows that blocking ALS mutation in the brain slowed disease initiation and progression

2014-11-19
(Press-News.org) LOS ANGELES (STRICTLY EMBARGOED UNTIL 5 P.M. EST on NOV. 11, 2014) - Lou Gehrig's disease, also known as amyotrophic lateral sclerosis, or ALS, might damage muscle-controlling nerve cells in the brain earlier in the disease process than previously known, according to research from the Cedars-Sinai Board of Governors Regenerative Medicine Institute. The findings, published in the Nov. 12 Journal of Neuroscience, could shift researchers' attention from the spinal cord to the brain's motor cortex as the disease's initial point of dysfunction.

"In this study, we show the exact progression of ALS in animals that have an inherited form of the disease, and we expose the brain's significant role in initiating the disease process thought previously to originate in the muscle or spinal cord," said Clive Svendsen, PhD, professor and director of the Board of Governors Regenerative Medicine Institute. "We did this by selectively removing the disease-causing mutation just from the brains of ALS animals, and found that this alone had a big impact on disease initiation and progression."

ALS causes weakness and gradual paralysis of muscles throughout the body, and although the timing and sequence of progression is unpredictable, it often begins in the arms or legs and eventually affects the breathing muscles in the chest. Patients generally live only three to five years after onset.

The disease is known to affect motor neurons - nerve cells that control muscles - in the brain, brainstem and spinal cord. It also inflicts damage in the nerve pathways extending from the spinal cord out to the muscles of the body. Breakdown of communication at the neuromuscular junctions - the points where nerve fibers connect to muscle fibers - is what ultimately leads to muscle weakness and failure.

In previous research using laboratory mice with the disease, the earliest, most obvious anatomical damage has been seen in the neuromuscular junctions and in the spinal motor neurons, called the lower motor neurons. Most ALS research has focused on these areas. But recent studies in both humans and lab mice have suggested that motor neurons in the brain - the upper motor neurons - may be involved in disease progression, although the extent and significance of this involvement has remained unknown. This study was designed to better define the process by which ALS progresses and to explore the role of brain motor neurons in disease development and progression.

Most animal studies of the disease are conducted with laboratory mice that have been genetically engineered and bred to model ALS, but for this research, investigators used rats with ALS because they more accurately portray the disease's variable course in humans.

"We found that spinal motor neurons die before symptoms begin and before nerve damage occurs between the spinal cord and the muscles. In fact, motor neuron death starts in the spinal cord and radiates out to the muscle and the brain over time. Motor neurons in the brain are not lost until the final stages of the disease, but starting very early in the process they appear to exist in a dysfunctional form. When we suppressed the ALS mutation in the brains of animals, onset of the disease was delayed, the animals lived longer, spinal motor neurons survived longer, and the neuromuscular junctions stayed healthy longer," said Svendsen, the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine.

"These results suggest that an early dysfunction of motor neurons in the brain may be a significant contributor to later disease development and progression, opening the possibility that experimental therapies targeting this 'upstream' dysfunction could have a beneficial impact on the disease's catastrophic 'downstream' effects," said Svendsen, the article's senior author.

Gretchen Thomsen, PhD, a scientist in Svendsen's laboratory and first author of the paper, said, "It is likely that dysfunction at a cellular level, without cell death, goes undetected for years prior to symptom onset and clinical diagnosis. It is imperative that we identify patients at high risk of developing ALS and devise and initiate treatments that can intervene before an irreversible cascade of motor neuron circuitry failure sets in."

INFORMATION:

This work was supported by the Board of Governors Regenerative Medicine Institute at Cedars-Sinai and the ALS Association. Other collaborators included Brian Kaspar, PhD, from the Research Institute at Nationwide Children's Hospital in Columbus, Ohio, supported by National Institutes of Health grant R01 NS644912.

Citation: The Journal of Neuroscience: "Delayed disease onset and extended survival in the SOD1G93A rat model of ALS following suppression of mutant SOD1 in the motor cortex," publishing Nov. 12, 2104



ELSE PRESS RELEASES FROM THIS DATE:

Home exercise can ease hopelessness in coronary heart disease patients

2014-11-18
Home exercise can ease feelings of hopelessness in people with coronary heart disease, according to a small study presented at the American Heart Association's Scientific Sessions 2014. Feeling hopeless can be dangerous because it can discourage people from taking healthful steps such as exercising or quitting smoking, said Susan L. Dunn, Ph.D., R.N., lead author of the study and a professor of nursing at Hope College in Holland, Michigan. People with hopelessness may also suffer from depression, which is marked by a loss of interest in activities they normally enjoy. "For ...

New wireless ECG saves treatment time for people with severe heart attacks

2014-11-18
A new trans-satellite wireless 12-lead ECG can identify the most severe type of heart attack swiftly and save significant time from ambulance to angioplasty, according to research presented at the American Heart Association's Scientific Sessions 2014. An ECG measures the electrical activity of the heart and helps medical personnel determine if a person had an ST-elevation myocardial infarction (STEMI). Angioplasty, also known as percutaneous coronary intervention (PCI), is a procedure in which an inflatable balloon opens a blocked artery to restore blood flow to the heart. During ...

People who gained weight after quitting smoking still had lower death risk

2014-11-18
In a small study in Japan, people who stopped smoking didn't face increased death risk if they gained weight, according to research presented at the American Heart Association's Scientific Sessions 2014. "Quitters had a significantly lower risk of death compared to smokers regardless of their weight change after they stopped smoking," said Hisako Tsuji, M.D., lead author of the study. Researchers compared deaths from all causes in 1,305 Japanese adults who quit smoking to deaths among 2,803 Japanese smokers. Participants in both groups were 65 percent men, average age ...

Education and feedback may help improve heart health among high-risk groups

2014-11-18
Using a smart phone app for education and feedback about heart-healthy behavior may decrease the risk for heart and blood vessel disease among young black women, researchers said in a pilot feasibility study presented at the American Heart Association's Scientific Sessions 2014. "We need to raise awareness among women and their healthcare providers of gender and racial differences in cardiovascular disease," said Jo-Ann Eastwood, Ph.D., study lead author and associate professor at the University of California, Los Angeles School of Nursing. "Women are social by nature, ...

Patients counseled on genetic heart disease risk feel they have more control over fate

2014-11-18
Adults counseled on their genetic risk of coronary heart disease believe they have more control over their fate, according to research presented at the American Heart Association's Scientific Sessions 2014. Researchers examined the impact of disclosing risk of 10-year heart disease with or without genetic risk information to 207 patients (48 percent male, average age 58) participating in Myocardial Infarction GENES (MI-GENES), a randomized controlled study. The study's key elements included a risk score based on established risk factors and a genetic risk score based ...

Healthy diet linked to decreased blood-pressure measurements

2014-11-18
A heart-healthy diet is related to decreased blood pressure measurements, researchers said in a study presented at the American Heart Association's Scientific Sessions 2014. Elevated blood pressure is a major risk factor for the development of heart and blood vessel disease. It is known that following U.S. dietary guidelines can decrease the risk for heart and blood vessel disease, their effects on specific blood pressure measurements were unclear. In this study, researchers found that blood pressure measurements were higher among study participants who did not follow ...

Social media strategy may increase public awareness about donor heart needs

2014-11-18
Using social media to deliver both emotional and concise medical content as well as the need for heart transplants and organs resulted in a higher engagement with members, according to research presented at the American Heart Association's Scientific Sessions 2014." "Social media has not been used extensively in the healthcare industry, and if we can effectively bridge the gap between health education and medicine using social networks and peer influence, we can potentially have many beneficial applications to the healthcare system," said Mohammad Soroya, lead author ...

Youths with a family history of substance use disorders have less efficient forebrain

2014-11-18
Youths with a family history of alcohol and other drug use disorders have a greater risk of developing substance-use disorders (SUDs) themselves than their peers with no such family histories. A new study examines forebrain activity in youths with and without a family history of SUDs. Findings indicate that youths with a family history have forebrain regions that function less efficiently. Researchers and clinicians know that youths with a family history of alcohol and other drug use disorders (FH+) have a greater risk of developing substance-use disorders (SUDs) ...

Chronic alcohol intake can damage white matter pathways across the entire brain

2014-11-18
Chronic misuse of alcohol results in measurable damage to the brain. A new study uses high-resolution structural magnetic resonance (MR) scans to compare the brains of individuals with a history of alcoholism versus those of healthy light drinkers. The abstinent alcoholics showed pronounced reductions in frontal and superior white matter tracts. Chronic misuse of alcohol results in measurable damage to the brain. Chronic drinking may be particularly damaging to the integrity of frontal white matter tracts, which can interfere with cognitive and inhibitory control ...

Childhood adversity hinders genetic protection against problem drinking in white men

2014-11-18
An alcohol metabolizing gene called ADH1B is strongly linked to risk for alcohol use disorders (AUDs). The His allele (genetic variant) at ADHD1B-rs1229984 is considered protective against AUDs. Experiencing adverse events during childhood, such as physical or sexual abuse or witnessing violence, is a well-documented risk factor for alcohol problems. A study of the effects of both the ADH1B gene and childhood adversity has found that under conditions of childhood adversity, the ADH1B His allele does not exert its protective effects against problem drinking in European-American ...

LAST 30 PRESS RELEASES:

Scientists model 'true prevalence' of COVID-19 throughout pandemic

New breakthrough to help immune systems in the fight against cancer

Through the thin-film glass, researchers spot a new liquid phase

Administering opioids to pregnant mice alters behavior and gene expression in offspring

Brain's 'memory center' needed to recognize image sequences but not single sights

Safety of second dose of mRNA COVID-19 vaccines after first-dose allergic reactions

Changes in disparities in access to care, health after Medicare eligibility

Use of high-risk medications among lonely older adults

65+ and lonely? Don't talk to your doctor about another prescription

Exosome formulation developed to deliver antibodies for choroidal neovascularization therapy

Second COVID-19 mRNA vaccine dose found safe following allergic reactions to first dose

Plant root-associated bacteria preferentially colonize their native host-plant roots

Rare inherited variants in previously unsuspected genes may confer significant risk for autism

International experts call for a unified public health response to NAFLD and NASH epidemic

International collaboration of scientists rewrite the rulebook of flowering plant genetics

Improving air quality reduces dementia risk, multiple studies suggest

Misplaced trust: When trust in science fosters pseudoscience

Two types of blood pressure meds prevent heart events equally, but side effects differ

New statement provides path to include ethnicity, ancestry, race in genomic research

Among effective antihypertensive drugs, less popular choice is slightly safer

Juicy past of favorite Okinawan fruit revealed

Anticipate a resurgence of respiratory viruses in young children

Anxiety, depression, burnout rising as college students prepare to return to campus

Goal-setting and positive parent-child relationships reduce risk of youth vaping

New research identifies cancer types with little survival improvements in adolescents and young adul

Oncotarget: Replication-stress sensitivity in breast cancer cells

Oncotarget: TERT and its binding protein: overexpression of GABPA/B in gliomas

Development of a novel technology to check body temperature with smartphone camera

The mechanics of puncture finally explained

Extreme heat, dry summers main cause of tree death in Colorado's subalpine forests

[Press-News.org] Cedars-Sinai study of Lou Gehrig's disease shifts 'origin' focus to brain's motor neurons
Most research aims at spinal motor neurons and nerve-muscle connections, but new study shows that blocking ALS mutation in the brain slowed disease initiation and progression