Using experimental autoimmune encephalomyelitis as a model to study the effect of prenatal stress on fetal programming

Solati, Jalal; Asiaei, Masoud; Hoseini, Mostafa Haji Molla

doi:10.1179/1743132812y.0000000032

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…54 Moreover, as mentioned above, systemic administration of LPS during pregnancy exacerbated EAE in the offspring. 43 Taken together, these results indicate that early life stress can exacerbate EAE in a sex-specific fashion, and suggest that MS risk in adulthood may be influenced by stressful events in childhood or in utero , differentially in males versus females.…”

Section: Effects Of Environmental Ms Risk Factors In Animal Models: Dmentioning

confidence: 68%

“…42 In contrast, administration of LPS during pregnancy exacerbated EAE in the offspring. 43 Since in both of these models LPS is delivered systemically at relatively high doses (similar to models of septic shock), these systems more likely to mimic a general sickness/stress response to a systemic infection rather than natural exposure to commensal microorganisms e.g. via mucosal surfaces.…”

Section: Effects Of Environmental Ms Risk Factors In Animal Models: Dmentioning

confidence: 99%

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Environmental factors acting during development to influence MS risk: insights from animal studies

Krementsov

Teuscher

2013

Mult Scler

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Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system with an increasing incidence in females. Epidemiological data strongly implicate environmental factors acting at the population level during gestation, childhood, and adulthood in the increasing incidence of MS. Several such factors have been implicated in disease risk, but their causality remains unproven, while other factors remain unknown. The understanding of risk factors acting during development is particularly limited. Animal studies could potentially bridge the gap between observational epidemiology and clinical intervention, providing not only direct evidence of causality for a given environmental agent, but also an opportunity to dissect the underlying molecular mechanisms. Given the short gestational and developmental period in rodents, effects of developmental exposure can also be readily addressed. Nonetheless, studies in this area have so far been few. In this review, we summarize the insights gleaned from studies that test environmental influences in animal models of MS, with a particular focus on gestational and early life exposures.

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Section: Effects Of Environmental Ms Risk Factors In Animal Models: Dmentioning

confidence: 68%

Section: Effects Of Environmental Ms Risk Factors In Animal Models: Dmentioning

confidence: 99%

Environmental factors acting during development to influence MS risk: insights from animal studies

Krementsov

Teuscher

2013

Mult Scler

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“…Among this plethora of diseases characterized by susceptibility to fetal programming, little is known about the impact of insults happening to the intrauterine life on multiple sclerosis (MS). While several preclinical studies have been carried out on the effects of environmental risk factors on MS during adulthood (Krementsov and Teuscher 2013 ), less is known on the influence of developmental stress exposure and only a few studies have addressed this gap by evaluating the impact of earlier post-natal events -such as neonatal handling and cross-fostering- in the experimental autoimmune encephalomyelitis (EAE) model of MS in rats (Laban et al 1995 ; Dimitrijević et al 1994 ) or in mice (Columba-Cabezas et al 2009 ; Case et al 2010 ).To our knowledge, the only scientific evidence on insults occurring specifically during pregnancy concerns the consequences of maternal infection on EAE course in the offspring (Solati et al 2012 ; Majidi-Zolbanin et al 2015 ). The behavioral and molecular effects of gestational exposure to stress on EAE course have not been investigated, and our work indeed represents the first study aiming to address this aspect.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Stress Impairs Spinal Cord Oligodendrocyte Maturation via BDNF Signaling in the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis

et al. 2020

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One of the most substantial and established environmental risk factors for neurological and psychiatric disorders is stress exposure, whose detrimental consequences hinge on several variables including time. In this regard the gestational period is known to present an intrinsic vulnerability to environmental insults and thus stressful events during pregnancy can lead to severe consequences on the offspring’s brain development with long-term repercussions throughout adulthood. On this basis, we investigated the long-lasting impact of prenatal stress exposure on the susceptibility to the experimental autoimmune encephalomyelitis (EAE), a well-established murine model of multiple sclerosis. Although stress is considered a triggering factor for this chronic, progressive, autoimmune disease, little is known about the underlying mechanisms. To this end, EAE was induced by immunization with MOG35-55/CFA and pertussis toxin administration in adult female C57BL/6 mice born from control or stressed dams exposed to restraint stress during the last days of gestation. Our results demonstrate that gestational stress induces a marked increase in the severity of EAE symptoms in adulthood. Further, we highlight an altered maturation of oligodendrocytes in the spinal cord of prenatally stressed EAE mice, as indicated by the higher levels of GPR17, a marker of immature oligodendrocyte precursor cells. These behavioral and molecular alterations are paralleled by changes in the expression and signaling of the neurotrophin BDNF, an important mediator of neural plasticity that may contribute to stress-induced impaired remyelination. Since several already marketed drugs are able to modulate BDNF levels, these results pave the way to the possibility of repositioning these drugs in multiple sclerosis.

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“…By using the common method, EAE was induced in female C57BL/6 mice. 18,19 Briefly, 200 µg of myelin oligodendrocyte glycoprotein peptide (MOG35-55; KJ Ross-Petersen ApS, Copenhagen, Denmark) was emulsified with the same volume of complete Freund's adjuvant (CFA; Sigma, F5881, USA) comprising 500 µg of heat-killed Mycobacterium tuberculosis (100 µl total volume); consequently, the subcutaneously emulsion was injected in both hind flanks of the mice. The animals as well received intraperitoneal injections of pertussis toxin (300 ng in 100 µL PBS; List Biological Lab, Campbell, CA, USA) when immunization occurred.…”

Section: Induction Of Eaementioning

confidence: 99%

Chitin Micro Particles Regulate Splenocytes Immune Response in Experimental Autoimmune Encephalomyelitis

Mami

Yeganeh

Farahani

et al. 2019

IJAAI

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Contrasting studies are reported on the induction of IL-10 and IFN-γ via chitin microparticles (CMPs) during immune stimulation. Our previous studies have shown marked protection among CMP treated Leishmania-infected mice via regulated IL-10/IFN-γ response, at the present study, once more, examined the inconsistent responses regarding the immunologic response of CMPS. To verify whether CMPs could indeed up-regulate IL-10/IFN-γ axis, isolated spleen cells from the myelin oligodendrocyte glycoprotein (MOG) induced experimental autoimmune encephalomyelitis (EAE) mice were cultured in the presence of MOG peptide and/or CMPs. The effects of CMPs on IL-10, IFN-γ and IL-17 production were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). Moreover, GATA binding protein 3 (Gata3), T-box transcription factor TBX21 (Tbx21), and RAR-related orphan receptor gamma (RORγT) expressions (real-time PCR) were investigated. MOG alone stimulated the production of IFN-γ (p≤0.004) but not, IL-10 (p≤0.140). MOG/chitin stimulation resulted in a significant increase in IFN-γ and IL-10 levels, respectively; (p≤0.004 and p≤0.003) rather than MOG. Additionally, the expression of Tbx21 (p≤0.001), but not Gata3 (p≤0.08), was increased in the MOG/chitin-treated spleen cells. All in all, CMP supports Gata3 independent IL-10 production and promotes Tbx21 dependent IFN-γ induction. These results, alongside our previous data, indicate that CMPs has particular adjuvant effects.

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Using experimental autoimmune encephalomyelitis as a model to study the effect of prenatal stress on fetal programming

Abstract: Therefore, the present research can provide evidence that prenatal stress may play a role in enhancing the clinical symptoms of experimental autoimmune encephalomyelitis/MS.

Cited by 6 publications

References 39 publications

Environmental factors acting during development to influence MS risk: insights from animal studies

Environmental factors acting during development to influence MS risk: insights from animal studies

Prenatal Stress Impairs Spinal Cord Oligodendrocyte Maturation via BDNF Signaling in the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis

Chitin Micro Particles Regulate Splenocytes Immune Response in Experimental Autoimmune Encephalomyelitis

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