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Endocrine Disruption of the Neuro-immune Interface

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Endocrine Disruption of the Neuro-immune Interface

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by the Collaborative on Health and the Environment

Building on the January 8, 2014 teleconference featuring Dr. Rodney Dietert on how the developing immune system is a target for endocrine disrupting chemicals, Dr. Jamie DeWitt discussed how certain cells of the immune system may mediate endocrine signals to direct aspects of brain development. She also described scenarios where endocrine disrupting chemicals can alter brain development by changing signals to the immune cells that can mediate development of sex specificity in the brain.

Sources: http://www.healthandenvironment.org/partnership_calls/13590

by the Collaborative on Health and the Environment

Building on the January 8, 2014 teleconference featuring Dr. Rodney Dietert on how the developing immune system is a target for endocrine disrupting chemicals, Dr. Jamie DeWitt discussed how certain cells of the immune system may mediate endocrine signals to direct aspects of brain development. She also described scenarios where endocrine disrupting chemicals can alter brain development by changing signals to the immune cells that can mediate development of sex specificity in the brain.

Sources: http://www.healthandenvironment.org/partnership_calls/13590

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Endocrine Disruption of the Neuro-immune Interface

  1. 1. Endocrine Disruption of the Neuro‐‐immune Interface Jamie DeWitt East Carolina University Brody School of Medicine dewittj@ecu.edu 1
  2. 2. What is the neuro‐immune interface? The interactions between the nervous and immune systems and the cross‐regulatory impacts of these interactions on both immune and nervous system function. ‐‐M.J. Carson in Molecular Mechanisms and Consequences of Immune and Nervous System Interactions OR What the immune system does to the nervous system and what the nervous system does to the immune system and how they respond. 2
  3. 3. The immune system can impact cognition 3 From: Kipnis, Derecki, Yang, and Scrable, Trends in Immunology, 2008.
  4. 4. Immune dysfunction underlies neurological diseases (?) 4 From: Dietert, DeWitt, Germolec, and Zelikoff, Environmental Health Perspectives, 2010.
  5. 5. Immune dysfunction can arise during development Misregulated Inflammation Inflammatory / Disease/Tissue Damage Autoimmunity Allergic Disease Normal Immune Response Immunosuppression and the identification of sensitizing 5 chemicals From: Dietert, DeWitt, Germolec, and Zelikoff, Environmental Health Perspectives, 2010.
  6. 6. But what about the endocrine system and EDCs? Nervous System Disease Health Endocrine System Immune System 6
  7. 7. 7 From: Bilbo and Schwartz, Frontiers in Neuroendocrinology, 2012.
  8. 8. An example: Brain sex development Microglia (cells of the immune system) respond to a postnatal surge of testosterone (a hormone that is converted to estrogen in the brain) to masculinize dendritic spines on neurons (nervous system). Microglia Are Essential to Masculinization of Brain and Behavior Lenz KM, Nugent BM, Haliyur R, and McCarthy MM The Journal of Neuroscience, 2013, 33:2761–2772 8
  9. 9. An example: Brain sex development From: Lenz, Nugent, Haliyur, and McCarthy, The Journal of Neuroscience, 2013. 9
  10. 10. An example: Brain sex development From: Lenz, Nugent, Haliyur, and McCarthy, The Journal of Neuroscience, 2013. 10
  11. 11. An example: Brain sex development From: Lenz, Nugent, Haliyur, and McCarthy, The Journal of Neuroscience, 2013. 11
  12. 12. An example: Brain sex development Brief summary of the Lenz et al. (2013) study: • Females given estrogen or prostaglandins postnatally, have masculinzied microglia. • Females given estrogen postnatally have masculinized sexual behavior as adults. •• When microglial activity is blocked, this masculinization of microglia and sexual behavior in females is prevented. • Males given a drug that blocks prostaglandin synthesis have feminized microglia. THEREFORE, hormone disruption during this sensitive early postnatal period can impact adult sexual behavior. 12
  13. 13. An example: Brain sex development But what happens during prenatal development? When males receive high doses of estrogen prenatally, they have feminized genitalia and hypermasculinized adult sexual behavior (K. McCoy, unpublished data). 13
  14. 14. An example: Brain sex development We propose that prenatally, exposure to EDCs can change how the immune system responds to postnatal hormones, leading to changes in brain development and adult sexual behavior. 14
  15. 15. An example: Brain sex development THEREFORE, , hormone disruption during this sensitive prenatal period can impact adult sexual behavior. As we learn more about how brain sex develops and how the endocrine, immune, and nervous systems interact, we find more and more complex critical windows of developmental exposure. End game: more research into the basic science of development is required before we can even begin to understand the extent to which exposure to EDCs may impact development. 15
  16. 16. Collaborators Dr. Rod Dietert, Cornell University Dr. Krista McCoy, East Carolina University Thank you! 16

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