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Stress For Newborns Could Weaken Immune System Later In Life

June 21, 2004 - Intense traumatic events, such as maternal separation, occurring early in the life of an infant may weaken its immune system, making it more susceptible to viral infections later in life that could trigger multiple sclerosis, reveals research at Texas A&M University.

The research, by a psychologist Mary Meagher from the College of Liberal Arts and an immunologist Jane Welsh from the College of Veterinary Medicine at Texas A&M, shows that exposure to prolonged maternal separation during the first two weeks of life altered immune, endocrine and behavioral responses to acute "Theiler's virus" infection in mice.

Theiler's virus attacks the central nervous system during the first few weeks of infection, which is accompanied by polio-like symptoms. If the virus persists in the central nervous system, a subsequent chronic phase of the disease develops which is similar to multiple sclerosis in humans.

Researchers use Theiler's virus to investigate the role of stress in autoimmune diseases, or diseases that cause the body to attack its own cells as if they were foreign pathogens - a similar process occurs in multiple sclerosis, Meagher explains.

In this study, infant mice that were subjected to maternal separation and later contracted Theiler's virus as adults demonstrated an increased amount of the virus, altered behavioral signs of infection and had a more difficult time getting over, or "clearing," the infection in its acute stage than did mice that were not separated from their mothers and later contracted the disease.

Such results, Meagher explains, suggest that the immune system is undergoing a critical period of development early in an organism's life, and that a considerable stressor can cause significant life-long alterations to the immune system that increase its vulnerability to diseases of the central nervous system later in life.

Previous studies have shown stress to play an important role in the contracting of multiple sclerosis in humans, finding that 80 percent of adults who contract the disease reported a stressful life event two years before its onset. Meagher's research takes that exploration a step further, examining how early life stress alters vulnerability to later viral infections of the central nervous system.

Her research is being conducted as part of the "Recovery of Function" program, a new interdisciplinary program that enrolls about 30 graduate students and is composed of 14 faculty members from seven departments in four colleges at Texas A&M - the Colleges of Liberal Arts, Veterinary Medicine, Agriculture and Life Sciences, and Medicine. The program focuses on research interests such as the loss and recovery of neural function following injury, infection, aging and neurodegenerative disease in laboratory animal models. In addition, the program is affiliated with several off-campus research centers in Houston, Galveston and Dallas that focus on both laboratory and clinical research.

Understanding how early stress affects the developing immune system could lead to interventions that prevent or reverse the harmful effects of newborn stress on disease predisposition, Meagher says. Some treatments could possibly include antidepressants and/or teaching coping mechanisms for individuals who are more likely to be susceptible to the disease, she adds.

Contact: Mary Meagher, (979)845-2564, via e-mail: m-meagher@tamu.edu or Ryan A. Garcia, (979) 845-4680 or via e-mail: rag@univrel.tamu.edu.

06/21/04


AggieDaily
Office of University Relations
Texas A&M University
(979) 845-4641

Int J Dev Neurosci. 1998 Feb;16(1):1-8.

Neonatal handling in EAE-susceptible rats alters NGF levels and mast cell distribution in the brain.

Manni L, Micera A, Pistillo L, Aloe L.

Institute of Neurobiology, CNR, Rome, Italy.

Maternal separation in neonatal rodents causes a wide range of behavioural and metabolic alterations, affecting the physiological response of the neuro-immune-endocrine system. For example, interference with the normal mother-infant interactions leads to an increased susceptibility to experimentally-induced allergic encephalomyelitis (EAE) in adult life. Since it has been reported that mast cells (MCs) participate in the pathophysiology of the autoimmune inflammatory disease multiple sclerosis (MS) and also EAE and that brain nerve growth factor (NGF) levels are altered in EAE, studied whether maternal separation and gentle manipulation (gentling) of neonatal Lewis rats perturb NGF levels or MC distribution in the brain. EAE-induction susceptibility in adult life was also evaluated and NGF levels and mast cell distribution within the hippocampus and thalamus were measured at 0, 10, 20 and 60 postnatal days. Our results show an exacerbation of clinical signs in rats separated from mothers where EAE was induced, a general decrease in NGF protein levels and MC number in the hippocampus during the first developmental period and significant increase in the number of MC in the hippocampus and the thalamus at young-adulthood (60 days of age). These results indicate that disruption of the maternal bond during early infancy may produce long-lasting alterations in the brain cellular and molecular environment, leading to increased susceptibility to EAE in adult life.

PMID: 9664217 [PubMed - indexed for MEDLINE]

Int J Neuropsychopharmacol. 2003 Dec;6(4):391-6.

Desipramine treatment reduces the long-term behavioural and neurochemical sequelae of early-life maternal separation.

MacQueen GM, Ramakrishnan K, Ratnasingan R, Chen B, Young LT.

Mood Disorders Program, McMaster University, Hamilton, Ontario, Canada. macqueng@mcmaster.ca

Primate and rodent models of maternal separation have shown that repeated postnatal separation of young from the mother results in long-term changes to neurohormonal systems relevant to depression. To date, however, it remains unclear whether rodents that experience postnatal maternal separation display specific behavioural or biochemical features of depression in adulthood and whether these changes can be prevented by treatment with antidepressant drugs. We report here that maternally separated mice showed significantly shorter swim times on the forced swim test and significantly lower levels of brain-derived neurotrophic factor in dentate gyrus and CA3 regions of the hippocampus compared to control mice when assessed in adulthood. Neither of these differences was apparent in maternally separated mice that received chronic treatment with the antidepressant desipramine after maternal separation. These results suggest that intervention following early stress may eliminate the long-term vulnerability to behavioural and biochemical dysfunction that occurs following this early chronic stress.

PMID: 14641986 [PubMed - indexed for MEDLINE]