(Press-News.org) CHAMPAIGN, Ill. -- Childhood trauma could affect the trajectory of multiple sclerosis development and response to treatment in adulthood, a new study in mice found.
Mice that had experienced stress when young were more likely to develop the autoimmune disorder and less likely to respond to a common treatment, researchers at the University of Illinois Urbana-Champaign found. However, treatment that activated an immune-cell receptor mitigated the effects of childhood stress in the mice.
Multiple sclerosis is a progressive autoimmune disease in which the body attacks and strips away the protective coating around neurons, resulting in a wide range of neurological symptoms. Both genetic and environmental factors play a role in MS development.
Previous work has shown that early-life trauma increases susceptibility to developing more severe MS, but researchers have not been able to determine how, said Makoto Inoue, a professor of comparative biosciences at Illinois. In the new study, published in Nature Communications, Inoue's group studied a mouse model of MS. The mice were genetically susceptible to experimental autoimmune encephalomyelitis, the model most widely used for studying MS.
The researchers watched the development and progression of EAE in mice that had been briefly separated from their mother and given a salene injection while young and compared it with mice that had not experienced the same stress.
"Mice that had early-life trauma were more susceptible to EAE disease development and suffered prolonged motor paralysis with severe neuronal damage in the central nervous system, which we found was caused by a heightened immune response," said graduate student Yee Ming Khaw, the first author of the study.
The researchers traced the EAE triggers to the immune system - in particular, a receptor on immune cells that binds to the stress hormone norepinephrine. The researchers found that childhood stress in the mice triggered a prolonged release of norepinephrine. The receptor was activated for long periods of time, which led the cells to decrease its expression - leaving the immune system less equipped to respond to the stress and inflammation of EAE.
Importantly, mice that developed EAE after stress in their childhoods did not respond to treatment with interferon beta, one of the initial therapies most widely prescribed to individuals with MS. Meanwhile, the drug effectively prevented EAE progression in mice without childhood stress, Khaw said.
Next, the researchers treated the mice with a compound that boosts the receptor's response. The treatment prevented paralysis and slowed damage to the spinal cord. In addition, mice that received the treatment responded to interferon beta treatment, though they had not responded before.
"This work suggests that individuals with experience of childhood trauma develop autoimmune disease with symptoms and mechanisms that greatly differ from their peers with no history of childhood trauma, and may need different medical treatment," Inoue said. "This receptor activator may be a therapeutic drug for MS patients with a history of childhood trauma."
Next, the researchers plan to verify the mechanisms of the receptor, and to perform translational studies to verify whether boosting the receptor in human patients with MS gives the same benefits as it did for the mice with EAE.
"We believe that the best approach to addressing autoimmune diseases in individuals with a history of childhood trauma or other risk factors is a comprehensive and personalized medicine approach that addresses the whole person," Inoue said.
INFORMATION:
The University of Illinois and the Sumitomo Foundation supported this work.
Editor's notes: To reach Makoto Inoue, call (217) 300-4085; email makotoi@illinois.edu.
The paper "Early-life-trauma triggers interferon-β resistance and neurodegeneration in a multiple sclerosis model via downregulated β1-adrenergic signaling" is available online (https://www.nature.com/articles/s41467-020-20302-0).
DOI: 10.1038/s41467-020-20302-0
It all sounds similar to a dance event - but are singles or couples dancing here? This was the question Ali Isbilir and Dr. Paolo Annibale at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) were trying to answer. However, their investigation did not involve a ballroom, but the cell membrane. The question behind their investigation: does a particular protein receptor on the surface of cancer and immune cells appear alone or connect in pairs?
The receptor is called "CXCR4" - the subject of heated debate among experts in recent years due to its mysterious relationship ...
(Boston)--There is a growing awareness of systematic inequality and structural racism in American society. Science and medicine are no exception, as evidenced by historical instances of discrimination and overt racism.
In a perspective piece in the Journal of the American Society of Nephrology, researchers from Boston University School of Medicine (BUSM), take an honest look at how the current practice of nephrology (kidney medicine) may have elements rooted in racist ideologies.
For twenty years, kidney function has been estimated based on lab tests and equations that consider ...
A combination of reduced-dose radiotherapy using intensity-modulated radiotherapy (IMRT) combined with concurrent cisplatin met the threshold for disease control and quality of life compared to the standard of care for good-risk patients with HPV-associated oropharyngeal squamous cell carcinoma on the NRG Oncology clinical trial NRG-HN002. The outcomes from this data justify the advancement of the reduced radiotherapy dose with cisplatin to a Phase III clinical trial setting in this population. These results were recently published in the Journal of Clinical Oncology.
"Currently, patients with HPV-associated ...
WHAT:
The earliest eye damage from prion disease takes place in the cone photoreceptor cells, specifically in the cilia and the ribbon synapses, according to a new study of prion protein accumulation in the eye by National Institutes of Health scientists. Prion diseases originate when normally harmless prion protein molecules become abnormal and gather in clusters and filaments in the human body and brain.
Understanding how prion diseases develop, particularly in the eye because of its diagnostic accessibility to clinicians, can help scientists identify ways to slow the spread of prion diseases. The scientists say their findings, published in the journal Acta Neuropathologica Communications, ...
Colorectal cancer is the third most common form of cancer. While 90% of cases are in people older than 50, there is an as-yet unexplained rising incidence in younger people.
Family history ranks high among risk factors for developing colorectal cancer, and people with such a history are often advised to get more frequent screening tests or start screening sooner than the recommended age of 45 years old. Those with a family history of cancer often seek out genetic tests to look for mutations linked to cancer risk. However, those tests don't always provide helpful information.
In a new paper in the American Journal of Human Genetics, Jacob Kitzman, Ph.D., of the ...
Scientists at Tokyo Institute of Technology (Tokyo Tech) produced and extensively characterized novel organic molecules with a long helical structure. Unlike previous helical molecules, these longer compounds exhibit special interactions between coils that could give rise to interesting optical and chemical properties with applications in light polarization, catalysis, and molecular springs.
More often than not, organic molecules with unique 3D structures bear physicochemical properties that cannot be found in other types of compounds. Helicenes, chains of simple benzene rings that adopt a helical structure, are a good ...
For species to survive in the wild, maintaining connectivity between populations is critical. Without 'wildlife corridors', groups of animals are isolated, unable to breed and may die out. In assessing wildlife connectivity, many aspects of the landscape are measured, but the impact of human behaviour has largely been overlooked. Now, an international team led by the University of Göttingen and Humboldt University Berlin, introduce the concept of 'anthropogenic resistance', which should be studied to ensure sustainable landscapes for wildlife and people ...
In northern Canada, the forest floor is carpeted with reindeer lichens. They look like a moss made of tiny gray branches, but they're stranger than that: they're composite organisms, a fungus and algae living together as one. They're a major part of reindeer diets, hence the name, and the forest depends on them to move nutrients through the ecosystem. They also, at least in parts of Quebec, are having a lot more sex than scientists expected. In a new study in the American Journal of Botany, researchers found that the reindeer lichens they examined have unexpected levels of genetic diversity, indicating that the lichens have been doing more gene-mixing with each other than the scientists would have guessed.
"We were surprised because this species of reindeer lichen had ...
(Singapore--January 29, 2021 11:00 p.m. SPT/10:00 a.m. EST)--On February 27, 2020, the flagship journal of the International Association for the Study of Lung Cancer, the Journal of Thoracic Oncology, published a case study that described two patients from Wuhan, China who recently underwent lung lobectomies for adenocarcinoma and were retrospectively found to have had COVID-19 at the time of surgery.
Eleven months later, the lung cancer research community gathered virtually at the IASLC 2020 World Conference on Lung Cancer Singapore to share a number of research ...
CHICAGO (January 29, 2021): Trauma patients and patients who need emergency surgery have little to no opportunity to get acquainted with the surgeon and team that will perform their operation. However, a large study has found that effective and meaningful physician communication is a more important contributor to the overall satisfaction of trauma patients and those having emergency surgery than it is for patients admitted to the hospital for medical reasons or for elective procedures.
The study was selected for the 2020 Southern Surgical Association Program and published as an "article in press" on the website of the Journal of the American College of Surgeons in advance of print.
The researchers found an unexpectedly significant effect of physician communication ...
