Childhood trauma may affect the developmental pathway of multiple sclerosis and response to treatment as an adult, a new study in found mice.
Mice that had gained weight when they were young were more likely to develop the autoimmune disorder and less likely to respond to common treatment, researchers at the University of Illinois Urbana-Champaign found. However, immunosuppressive receptor-activated treatment reduced the effect of childhood stress in the mice. The study was published in the journal Nature Communications.
Multiple sclerosis is a progressive autoimmune disease in which the body invades and removes the protective covering around neurons, leading to a wide range of neurological symptoms. Both genetic and environmental factors play a role in the development of MS.
Previous work has shown that early life trauma increases vulnerability to developing more severe MS, but researchers have not been able to figure out how, said Makoto Inoue, professor of bio- comparative experience in Illinois. In the new study, the Inoue group studied a mouse model of MS. The mice were genetically predisposed to experimental autoimmune encephalomyelitis, the most widespread model for the study of MS.
The researchers monitored the development and progression of EAE in mice recently separated from their mother and given a salene injection while young and compared it to mice not received the same weight.
“Mice with early life trauma were more prone to developing EAE disease and suffered prolonged motor paralysis with severe neuronal damage in the central nervous system, which we found to be caused by a higher immune response,” said a student graduate Yee Ming Khaw, first author of the study.
The researchers monitored EAE stimuli to the immune system – specifically, a receptor on immune cells that binds to the stress hormone norepinephrine. The researchers found that childhood weight gain in the mice induced prolonged release of norepinephrine. The receptor was activated for a long time, which caused the cells to reduce the expression – leaving the immune system less equipped to deal with stress and inflammation of EAE.
Importantly, mice that developed EAE after childhood weight did not respond to treatment with interferon beta, one of the most commonly prescribed original treatments for individuals with MS. At the same time, the drug inhibited the progression of EAE in mice without childhood weight loss, Khaw said.
Next, the researchers treated the mice with a fertilizer that stimulates the receptor response. The treatment prevented paralysis and delayed spinal damage. In addition, mice that received the treatment responded to beta interferon treatment, although they had not responded before.
“This work suggests that individuals who experience childhood trauma develop the autoimmune disease with symptoms and mechanisms that are significantly different from their peers who do not have a history of pregnancy. childhood, and may need different medical treatment, “said Inoue.
“This receptor activator may be a therapeutic drug for MS patients with a history of childhood trauma.”
Next, the researchers plan to test the receptor mechanisms, and conduct translational studies to determine whether elevator uptake in human patients with MS provides the same benefits as made for the mice with EAE.
“We believe that the best way to treat autoimmune diseases in individuals with a history of childhood trauma or other risk factors is a holistic and personalized treatment approach that treats the whole person,” said Inoue.
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