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Autism and Mast Cells

PHM142 Fall 2013 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson. Autism and Mast Cells. By: Abdullah Aboukarr, Yousef Al-Enzi, Jeffrey Mesdag , Mohamed Debouk. November 20, 2013. Autism. Autism. Autistic spectrum disorder

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Autism and Mast Cells

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  1. PHM142 Fall 2013 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson Autism and Mast Cells By: Abdullah Aboukarr, Yousef Al-Enzi, Jeffrey Mesdag, Mohamed Debouk November 20, 2013

  2. Autism

  3. Autism • Autistic spectrum disorder • Stereotypic behaviours, language deficit, behaviour abnormalities • Affects 1 in 100 children worldwide

  4. Diagnosis • Can be diagnosed by 2 years of age • Specific behaviours, communication delays, and/or developmental disabilities (no medical test) • Diagnostic and Statistical Manual of Mental Disorders

  5. Causes • Genetic • Environmental Factors • Autoimmune Disease

  6. Mast Cells • Leukocytes derived from haematopoetic cells involved in immunity and inflammation • Located in GI tract, brain (diancephalon), connective tissue • Mature mast cells exist in tissues under nonpathological conditions.

  7. Mast Cell Activation • Cell-mediated release of IL-6 and TNF-α • Pre-stored TNF-α • MCP-1 chemotaxis • Disruption of the BBB

  8. Non-Immune Triggered Stimulation • Stress-released NT and CRH • Contributes to BBB disruption • NT increases expression of CRH receptor-1 • NT stimulates release of histamine in rodent peritoneal mast cells

  9. Non-Immune Triggered Stimulation

  10. Immune Triggered Stimulation • Mast cells can be overstimulated by allergens • IgE antibodies bind to mast cells; recognize allergens by identifying specific proteins • Cascade initiated to release histamines and destroy allergenic cells • Result is increased inflammation

  11. Immune Triggered Stimulation

  12. Treatment • No current effective treatments, just therapies and educational tools to assist autistic learning and development • Luteolin • Mast cell inhibitor • Decreased IL-6 release • Has been shown to inhibit autistic-like behaviour in mice • Awaiting clinical trials! • CRH and NT?

  13. Summary • Autism spectrum disorders include autistic disorder, Asperger's disorder, and pervasive developmental disorder. • Diagnosis is based on specific behaviours, communication delays, and developmental disabilities. • Common characteristics include lack of imaginative/social play, difficulty making friends with own age group, inability to sustain a conversation, difficulty staying on task, and no eye contact • Causes of Autism are genetic, environmental, and autoimmune. • Mast cells are leukocytes derived from haematopoetic cells involved in immunity and inflammation found in the brain, GI tract, and connective tissue. • Cytokines IL-6 and TNF are released from mast cells. They are implicated in disruption of the BBB. • Stimulation of mast cells can be immune or non-immune. • No current effective treatments exist, just therapies and educational tools to assist autistic learning and development. • A promising flavonoid, Luteolin may serve as a novel therapeutic agents for the treatment of ASD becauseit is shown to inhibit mast cells, decreases IL-6 release, and inhibits autistic-like behaviour in mice.

  14. References • Theoharides, Theoharis C., et al. "Mast cell activation and autism." Biochimica et BiophysicaActa (BBA)-Molecular Basis of Disease 1822.1 (2012): 34-41. • Metcalfe, Dean D., Dana Baram, and Yoseph A. Mekori. "Mast cells." Physiological reviews 77.4 (1997): 1033-1079. • Angelidou, Asimenia, et al. "Brief report:“allergic symptoms” in children with autism spectrum disorders. more than meets the eye?." Journal of autism and developmental disorders 41.11 (2011): 1579-1585. • Theoharides, Theoharis C., et al. "The “missing link” in autoimmunity and autism: Extracellular mitochondrial components secreted from activated live mast cells." Autoimmunity reviews 12.12 (2013): 1136-1142. • Asadi, Shahrzad, and Theoharis C. Theoharides. "Corticotropin-releasing hormone and extracellular mitochondria augment IgE-stimulated human mast-cell vascular endothelial growth factor release, which is inhibited by luteolin." Journal of Neuroinflammation 9.1 (2012): 85. • "Understanding ASDs: Screening, Assessment and Diagnosis." Autism Society Canada. N.p., 11 Oct. 2010. Web. 16 Nov. 2013. <http://www.autismsocietycanada.ca/index.php?option=com_content&view=article&id=19&Itemid=53>. • Theoharides, Theoharis C., ShahrzadAsadi, and Arti B. Patel. "Focal brain inflammation and autism." Journal of neuroinflammation 10.1 (2013): 46. • Theoharides, Theoharis C., and Robert Doyle. "Autism, gut-blood-brain barrier, and mast cells." Journal of clinical psychopharmacology 28.5 (2008): 479-483.

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