Abstract
BackgroundMultiple sclerosis (MS) is the endpoint of a complex and still poorly understood process which results in inflammation, demyelination and axonal and neuronal degeneration. Since the first description of MS, psychological stress has been suggested to be one of the trigger factors in the onset and/or relapse of symptoms. However, data from animal models of MS, such as experimental autoimmune encephalomyelitis (EAE) are inconsistent and the effect of stress on EAE onset and severity depends on duration and time of application of the stress protocol and the underlying mechanisms.MethodsDark Agouti rats were inoculated with MOG/CFA to induce EAE, and an immobilisation stress protocol with two different durations (12 and 21 days, starting at the moment of MOG-inoculation) was applied in order to analyse the effect of stress on disease onset and neuroinflammation.ResultsTwelve days of stress exposure increased EAE clinical score in Dark Agouti rats. In addition, these animals presented higher levels of MMP-9 and proinflammatory PGE2 in spinal cord. In contrast, animals chronically exposed to stress (21 days) showed a significantly lower incidence of EAE clinical signs and reduced myelin loss, leukocyte infiltration and accumulation of inflammatory/oxidative mediators in spinal cord. Interestingly, chronically stressed animals showed a parallel increase in levels of the anti-inflammatory prostaglandin 15d-PGJ2, the main endogenous agonist of PPARγ.ConclusionsOur results demonstrate that, depending on duration, stress exposure elicits opposite effects on PGE2/15d-PGJ2 ratios in spinal cord of EAE-induced Dark Agouti rats. Further studies are needed to elucidate if these changes in prostaglandin balance are sufficient to mediate the differences in clinical score and inflammation here reported, and to establish the potential utility of pharmacological intervention in MS directed toward anti-inflammatory pathways.
Highlights
Multiple sclerosis (MS) is the endpoint of a complex and still poorly understood process which results in inflammation, demyelination and axonal and neuronal degeneration
After 21 days of experiment, animals from the EAE group showed higher clinical score than those submitted to 6 hours of daily immobilisation stress (EAE+S group) (1.88 vs 1.54, p < 0.05; according to following clinical score: 0, no disease; 1. tail paralysis; 2. hind limb weakness; 3. hind limb paralysis; 4. hind limb paralysis plus forelimb weakness; 5. moribund or dead)
EAE induced a significant increase in plasma corticosterone levels on day 21 after inoculation with myelin oligodendrocyte glycoprotein (MOG)/complete Freund’s adjuvant (CFA) (EAE: 451,1 ± 53,37 ng/mL vs control: 134,7 ± 21,16 ng/mL)
Summary
Multiple sclerosis (MS) is the endpoint of a complex and still poorly understood process which results in inflammation, demyelination and axonal and neuronal degeneration. Multiple sclerosis (MS) is a chronic, disabling disease of the central nervous system (CNS), affecting more than 2 million people worldwide. It has an autoimmune component and is characterized by chronic neuroinflammation with lymphocyte infiltration into the CNS, myelin loss, gliosis, various degrees of axonal and oligodendrocyte pathology and progressive neurological dysfunction [1]. While studies of animal models have potential to explain the pathophysiological basis of these interactions, data from these animal models are inconsistent (reviewed in [8]): in general, acute stress before inoculation increases the severity of the disease [9,10], while chronic stress has been reported to have a protective role, but only when applied prior to induction of EAE [11,12,13]. Whitacre et al, (1998) have shown that stress exposure after induction of relapsing EAE has no protective effect [13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
