Amelioration of Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice by Photobiomodulation Induced by 670 nm Light

The approved immunomodulatory agents for the treatment of multiple sclerosis (MS) are only partially effective. It is thought that the combination of immunomodulatory and neuroprotective strategies is necessary to prevent or reverse disease progression. Irradiation with far red/near infrared light, termed photobiomodulation, is a therapeutic approach for inflammatory and neurodegenerative diseases. Data suggests that near-infrared light functions through neuroprotective and anti-inflammatory mechanisms. We sought to investigate the clinical effect of photobiomodulation in the Experimental Autoimmune Encephalomyelitis (EAE) model of multiple sclerosis.The clinical effect of photobiomodulation induced by 670 nm light was investigated in the C57BL/6 mouse model of EAE. Disease was induced with myelin oligodendrocyte glycoprotein (MOG) according to standard laboratory protocol. Mice received 670 nm light or no light treatment (sham) administered as suppression and treatment protocols. 670 nm light reduced disease severity with both protocols compared to sham treated mice. Disease amelioration was associated with down-regulation of proinflammatory cytokines (interferon-γ, tumor necrosis factor-α) and up-regulation of anti-inflammatory cytokines (IL-4, IL-10) in vitro and in vivo.These studies document the therapeutic potential of photobiomodulation with 670 nm light in the EAE model, in part through modulation of the immune response

Understanding the Immune Response: Friend or Foe

The immune response is an army of cells and other factors that has evolved to protect us from disease while ignoring our own tissues. When functioning properly, it effectively serves this function. However, when mechanisms fail, the immune response can target our own tissues leading to disease, such as Type I diabetes or multiple sclerosis. Other times, an over-zealous immune response can lead to chronic inflammation. Such is the case with diabetic or pressure ulcers, or more acute damage, such as the cytokine storm contributing to COVID-19 pathology. Join Dr. Jeri-Anne Lyons, AVP for Research and Dean of the Graduate School, to gain insight into the immune response and its role in health and disease. ASL Interpreter on-scree

Office of Research & Sponsored Projects Support and Services

Join Dr. Jeri Lyons, Associate Vice President for Research and Dean of the Graduate School, to learn about how the Office of Research and Sponsored Programs can support your scholarship

Webinar: Building Your Research Program: Developing Your Research Plan

Dr. Jeri-Anne Lyons, Associate Vice President for Research and Dean of the Graduate School shares strategies for developing a short- and long-term research plan. This session is designed for early career researchers and/or those faculty who have not yet found success with securing external grant funding

Webinar: Building Your Research Program: Developing Your Research Program

In this second session, Dr. Jeri-Anne Lyons shares strategies for finding funding opportunities and considerations for building research collaborations. This session is designed for early career researchers and/or those faculty who have not yet found success with securing external grant funding

Myostatin expression, lymphocyte population, and potential cytokine production correlate with predisposition to high-fat diet induced obesity in mice.

A strong relationship exists between increased inflammatory cytokines and muscle insulin resistance in obesity. This study focused on identifying a relationship between metabolic propensity and myostatin expression in muscle and spleen cells in response to high-fat diet intake. Using a comparative approach, we analyzed the effects of high-fat diet intake on myostatin and follistatin expression, spleen cell composition, and potential cytokine expression in high-fat diet induced obesity (HFDIO) resistant (SWR/J) and susceptible (C57BL/6) mice models. Results demonstrated overall increased myostatin expression in muscle following high-fat diet intake in HFDIO-susceptible mice, while myostatin expression levels decreased initially in muscle from high-fat diet fed resistant mice. In HFDIO-resistant mice, myostatin expression decreased in spleen, while myostatin increased in spleen tissue from HFDIO-susceptible mice. Proinflammatory cytokine (IL-17, IL-1β, and IFNγ) potential increased in splenocytes from HFDIO-susceptible mice. In comparison, C57BL/6 mice fed a high-fat diet exhibited higher frequencies of CD4(+)/CD44(hi) and CD8(+)/CD44(hi) cells in the spleen compared to control fed mice. Together, these results suggest that susceptibility to high-fat diet induced obesity could be influenced by local myostatin activity in a tissue-specific manner and that splenocytes exhibit differential cytokine production in a strain-dependent manner. This study sets the stage for future investigations into the interactions between growth, inflammation, and metabolism

Photobiomodulation induced by 670 nm light ameliorates MOG35-55 induced EAE in female C57BL/6 mice: a role for remediation of nitrosative stress.

Experimental autoimmune encephalomyelitis (EAE) is the most commonly studied animal model of multiple sclerosis (MS), a chronic autoimmune demyelinating disorder of the central nervous system. Immunomodulatory and immunosuppressive therapies currently approved for the treatment of MS slow disease progression, but do not prevent it. A growing body of evidence suggests additional mechanisms contribute to disease progression. We previously demonstrated the amelioration of myelin oligodendrocyte glycoprotein (MOG)-induced EAE in C57BL/6 mice by 670 nm light-induced photobiomodulation, mediated in part by immune modulation. Numerous other studies demonstrate that near-infrared/far red light is therapeutically active through modulation of nitrosoxidative stress. As nitric oxide has been reported to play diverse roles in EAE/MS, and recent studies suggest that axonal loss and progression of disability in MS is mediated by nitrosoxidative stress, we investigated the effect of 670 nm light treatment on nitrosative stress in MOG-induced EAE.Cell culture experiments demonstrated that 670 nm light-mediated photobiomodulation attenuated antigen-specific nitric oxide production by heterogenous lymphocyte populations isolated from MOG immunized mice. Experiments in the EAE model demonstrated down-regulation of inducible nitric oxide synthase (iNOS) gene expression in the spinal cords of mice with EAE over the course of disease, compared to sham treated animals. Animals receiving 670 nm light treatment also exhibited up-regulation of the Bcl-2 anti-apoptosis gene, an increased Bcl-2:Bax ratio, and reduced apoptosis within the spinal cord of animals over the course of disease. 670 nm light therapy failed to ameliorate MOG-induced EAE in mice deficient in iNOS, confirming a role for remediation of nitrosative stress in the amelioration of MOG-induced EAE by 670 nm mediated photobiomodulation.These data indicate that 670 nm light therapy protects against nitrosative stress and apoptosis within the central nervous system, contributing to the clinical effect of 670 nm light therapy previously noted in the EAE model

Myostatin is attenuated in spleens of HFDIO-resistant mice fed high fat.

<p>Molecular regulation of <i>myostatin</i> (<i>MSTN</i>) mRNA levels using quantitative real-time PCR. <i>Myostatin</i> mRNA levels in muscle from C57BL/6 (a) and SWR/J (c) and spleen from C57BL/6 (b) and SWR/J (d). Muscle and spleen samples were taken at 3, 6, 9, and 12 wk on the dietary treatment. (e) RT-PCR analysis of <i>myostatin</i> mRNA expression in different tissues for verification. Mar) 100 bp ladder, Spl) whole spleen, Leu) isolated leukocytes (CD3/CD28), mus) pooled skeletal muscle, Adi) adipose tissue, and ntc) no template control. * demonstrates between dietary treatment differences at a given time, P<0.05.</p