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Regular exercise "improves cognitive function and synaptic and neuronal pathology" in EAE

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  • Regular exercise "improves cognitive function and synaptic and neuronal pathology" in EAE

    Exercise protects from hippocampal inflammation and neurodegeneration in experimental autoimmune encephalomyelitis

    Author links open overlay panelFrancesca RomanaRizzoa1LiviaGuadalupiab1KriziaSannaaValentinaVannibDiegoFresegnabFrancescaDe VitocAlessandraMusellabdSilviaCaiolicSaraBallettaaSilviaBullittaabAntonioBrunoacEttoreDolcettiacMarioStampanoni BassicFabioButtaricLuanaGiliocGeorgiaMandolesibdDiegoCentonzeacAntoniettaGentileb rights and content


    •Running wheel ameliorates motor disability and cognitive performance in EAE mice.
    •Exercise prevents the loss of parvalbumin-positive interneurons in the EAE hippocampus.
    •Abnormal synaptic plasticity in EAE CA1 area is corrected by exercise.
    •Exercise reduces microgliosis and inflammation in the CA1 area of EAE hippocampus.


    Exercise is increasingly recommended as a supportive therapy for people with Multiple Sclerosis (pwMS). While clinical research has still not disclosed the real benefits of exercise on MS disease, animal studies suggest a substantial beneficial effect on motor disability and pathological hallmarks such as central and peripheral dysregulated immune response. The hippocampus, a core area for memory formation and learning, is a brain region involved in MS pathophysiology. Human and rodent studies suggest that the hippocampus is highly sensitive to the effects of exercise, the impact of which on MS hippocampal damage is still elusive.

    Here we addressed the effects of chronic voluntary exercise on hippocampal function and damage in experimental autoimmune encephalomyelitis (EAE), animal model of MS. Mice were housed in standard or wheel-equipped cages starting from the day of immunization and throughout the disease course. Although running activity was reduced during the symptomatic phase, exercise significantly ameliorated motor disability. Exercise improved cognition that was assessed through the novel object recognition test and the nest building in presymptomatic and acute stages of the disease, respectively. In the acute phase exercise was shown to prevent EAE-induced synaptic plasticity abnormalities in the CA1 area, by promoting the survival of parvalbumin-positive (PV+) interneurons and by attenuating inflammation. Indeed, exercise significantly reduced microgliosis in the CA1 area, the expression of tumour necrosis factor (TNF) in microglia and, to a lesser extent, the hippocampal level of interleukin 1 beta (IL-1β), previously shown to contribute to aberrant synaptic plasticity in the EAE hippocampus. Notably, exercise exerted a precocious and long-lasting mitigating effect on microgliosis that preceded its neuroprotective action, likely underlying the improved cognitive function observed in both presymptomatic and acute phase EAE mice.

    Overall, these data provide evidence that regular exercise improves cognitive function and synaptic and neuronal pathology that typically affect EAE/MS brains.

    Graphical abstract

    Dave Bexfield

  • #2
    Here's another EAE study that also noticed significant changes due to exercise. (journal preprint)

    Effect of six weeks forced and voluntary training before EAE induction on the expression of some adhesive molecules affecting the blood-brain barrier permeability

    Document Type : original article

    1 PhD student

    2 Associate Professor of Tehran university

    3 Professor of Tehran university



    Purpose: Nearly 2.5 million people worldwide have multiple sclerosis, a chronic neuro-inflammatory disease of the brain and spinal cord that is a common cause of severe physical disability in young people, especially women. Therefore, the aim of this study was to investigate the effect of forced and voluntary training before EAE induction on the expression of adhesive molecule (ICAM-1 and VCAM-1) affecting the blood-brain barrier permeability in C57BL/6 mice.

    Methods: 28 female C57BL/6 mice with weight 182 g and age 71 weeks were randomly divided to 4 groups of forced training (n = 12), voluntary training(n=12), EAE control (n = 8) and healthy control (n = 8). To perform the forced training, the mice performed swimming for 30 minutes 5 days/week for 6 weeks. Also to perform the voluntary training, the mice performed running wheel for 1 hour 5 days/week for 6 weeks. After that ICAM-1 and VCAM-1 gene expression was measured by RT-PCR. In data analysis, one-way ANOVA and Tukey's post-hoc test were applied to determine the difference between the groups.

    Results: Five weeks recording clinical signs after EAE induction showed a significant difference between the scores of the two training groups and EAE control (P <0.05). Also, the expression of ICAM-1 and VCAM-1 adhesive molecules significantly decreased in the forced and voluntary groups compared to EAE control (P <0.05), but the forced and voluntary groups significantly did not differ from the healthy control group (P> 0.05).

    Conclusions: The forced and voluntary training appears to reduce the blood-brain barrier permeability by reducing the expression of ICAM-1 and VCAM-1 adhesive molecules.
    Dave Bexfield


    • #3
      And another. Probiotics didn't perform as well on their own (ya gotta put in the work). FYI: Interleukin (IL): any of a group of naturally occurring proteins that mediate communication between cells. Interleukins regulate cell growth, differentiation, and motility. They are particularly important in stimulating immune responses, such as inflammation.-D

      Clinical and Experimental Neuroimmunology


      Effects of exercise training with Lactobacillus plantarum intake on Iba-1, GFAP, IL-6, and IL-1β in cuprizone-induced demyelination mouse model of multiple sclerosis

      Donya Sajedi, Ramin Shabani, Alireza Elmieh
      First published: 23 August 2021
      This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/cen3.12673


      Multiple sclerosis (MS) is a central nervous system (CNS) disorder characterized by inflammation, demyelination, and neurodegeneration. It has been suggested that exercise and intake of probiotics might influence MS pathology and, thereby, slow down the disease process in MS patients. Therefore, this study aimed to investigate the effect of exercise training with Lactobacillus plantarum intake on Ionized calcium-binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), interleukin (IL)-6, and IL-1β in cuprizone (CPZ)-induced demyelination mouse model of MS.

      Mice were exposed to CPZ for 13 weeks. In the fifth week, motor and balance tests were performed on them. The mice (n=5 per group) were randomly divided into five groups: control (C), MS, MS with exercise (MS+Exe), MS with probiotics (MS+Pro), and MS with probiotics and exercise (MS+Pro+Exe). The exercise groups performed aerobic exercises 5 days a week for 2 months. The mice received probiotic by gavage. One day after the interventions finished, the mice were sacrificed. Biochemical and molecular biology analyses were performed.

      Iba1 and GFAP protein expression values in MS+Pro+Exe, MS+Pro, and MS+Exe groups showed a significant decrease compared to the MS group (P<0.05). Also, GFAP gene expression in intervention groups showed an insignificant decrease (P>0.05). The IL-6 and IL-1β values in the MS+Exe and MS+Pro+Exe groups showed a significant decrease compared to the MS group (P < 0.05).

      Exercise with the intake of probiotics improved demyelination in the CPZ-induced demyelination mouse model of MS.
      Dave Bexfield