hormone (CRH), neurotensin (NT) and substance P (SP) are secreted under stress and can stimulate MC, necessary for allergic reactions, to release inflammatory mediators that could contribute to ME/ CFS symptoms directly or via activation of microglia. We showed that CRH and NT act synergistically to stimulate MC to secrete VEGF, which increases permeability of the blood-brainbarrier (BBB) and would allow entry of toxins in the brtain. We also showed that NT can activate microglia to secrete IL-1beta. Moreover, we showed that the combined action of SP and the alarmin IL-33 lead to impressive amounts of TNF secretion from human MC. We further investigated the effect of combining ip injection of polyinosinic:polycytidylic acid [poly(I:C)], to mimic a viral infection, with 15 min forced cold swim stress, to mimic exercise and stress, on female C57BL/6 mice locomotor activity, as well as brain gene expression and serum levels of inflammatory mediators. Treated mice showed decreased locomotor activity over 72 hrs, while serum levels of TNF, IL-6 and KC (IL-8/CXCL8 murine homologue), as well as their gene expression in the brain, were increased increased. When other mice were provided with chow high in isoflavones for 2 weeks prior to treatment, this intervention reversed the reduced locomotor activity and minimized the increased serum levels and gene expression of the proinflammatory mediators. Moreover, the unique natural flavonoid, tetramethoxyluteolin potently inhibited both human cultured MC and microglia activation. We are presently seeking funding to measure these neuropeptides and cytokines in the blood of ME/CFS patients before and after exercise, as well as develop an intranasal tetramethoxyluteolin formulation for direct delivery to the hypotalamus through the cribriform plexus (Funded by an Anonymus grant). References from this article will be in the online version of the journal. Associate Professor Mady Hornig Associate Professor, Center for Infection and Immunity (CII), Columbia University Mailman School of Public Health New York, USA Mady Hornig, MA, MD is a physician-scientist in the Center for Infection and Immunity (CII) at the Columbia University Mailman School of Public Health where she serves as Director of Translational Research and is an associate professor of epidemiology. Her research focuses on the role of microbial, immune, Page 50 of 56 www.investinme.org and toxic stimuli in the development of neuropsychiatric conditions, including autism, PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection), mood disorders and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). She is widely known both for establishing animal models that identify how genes and maturational factors interact with environmental agents to lead to brain disorders and for her work clarifying the role of viruses, intestinal microflora and xenobiotics in autism and other neuropsychiatric illnesses that may be mediated by immune mechanisms. Under her direction, proteomic analyses of umbilical cord samples are identifying potential birth biomarkers for autism in a prospective study in Norway, the Autism Birth Cohort (ABC). She established that there was no association between intestinal measles virus transcripts and autism, and, with Brent Williams and W. Ian Lipkin at CII, has found altered expression of genes relating to carbohydrate metabolism and inflammatory pathways and differences in the bacteria harboured in the intestines of children with autism. She also leads projects examining the influence of immune molecules on brain development and function and their role in the genesis of schizophrenia, major depression, and cardiovascular disease comorbidity in adults, and directs the Chronic Fatigue initiative Pathogen Discovery and Pathogenesis Project at CII. In 2004, Dr. Hornig presented to the Institute of Medicine Immunization Safety Review Committee and testified twice before congressional subcommittees regarding the role of infections and toxins in autism pathogenesis. Her work in ME/CFS is establishing immune profiles and helping to identify pathogens that may be linked to disease. Abstract: Abstract not available at time of printing. Professor Maureen Hanson Director, Center for Enervating Neuroimmune Disease Liberty Hyde Bailey Professor, Department of Molecular Biology and Genetics, Cornell University, USA Maureen Hanson is Liberty Hyde Bailey Professor in the Department of Molecular Biology and Genetics at Cornell University in Ithaca, NY. Previously she was on the faculty of the Department of Biology at the University of Virginia in Charlottesville and an NIH NRSA postdoctoral fellow at Harvard, where she also completed her Ph.D. Invest in ME research (Charity Nr. 1153730)
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