Focal brain inflammation and autism

• Published in: Journal of neuroinflammation Vol. 10; no. 1; p. 46
• Main Authors: Theoharides, Theoharis C, Asadi, Shahrzad, Patel, Arti B
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09.04.2013; BioMed Central
• Subjects: Animals; Autism; Autistic Disorder - etiology; Autistic Disorder - metabolism; Autistic Disorder - pathology; Bioflavonoids; Brain - immunology; Brain - metabolism; Brain - pathology; Brain research; Brain-derived neurotrophic factor; Cells; Child; Children; Cytokines; Epigenetic inheritance; Flavones; Flavonoids; Gene mutations; Health aspects; Humans; Hypersensitivity - etiology; Hypersensitivity - metabolism; Hypersensitivity - pathology; Inflammation; Inflammation - complications; Inflammation - metabolism; Inflammation - pathology; Kinases; Neurophysiology; Neuropsychiatry; Phosphatases; Physiological aspects; Proteins; Review; Rodents; Signal Transduction - immunology; Stress, Psychological - etiology; Stress, Psychological - metabolism; Stress, Psychological - pathology; Vascular endothelial growth factor; United States
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/1742-2094-10-46

Increasing evidence indicates that brain inflammation is involved in the pathogenesis of neuropsychiatric diseases. Autism spectrum disorders (ASD) are characterized by social and learning disabilities that affect as many as 1/80 children in the USA. There is still no definitive pathogenesis or reliable biomarkers for ASD, thus significantly curtailing the development of effective therapies. Many children with ASD regress at about age 3 years, often after a specific event such as reaction to vaccination, infection, stress or trauma implying some epigenetic triggers, and may constitute a distinct phenotype. ASD children respond disproportionally to stress and are also affected by food and skin allergies. Corticotropin-releasing hormone (CRH) is secreted under stress and together with neurotensin (NT) stimulates mast cells and microglia resulting in focal brain inflammation and neurotoxicity. NT is significantly increased in serum of ASD children along with mitochondrial DNA (mtDNA). NT stimulates mast cell secretion of mtDNA that is misconstrued as an innate pathogen triggering an auto-inflammatory response. The phosphatase and tensin homolog (PTEN) gene mutation, associated with the higher risk of ASD, which leads to hyper-active mammalian target of rapamycin (mTOR) signalling that is crucial for cellular homeostasis. CRH, NT and environmental triggers could hyperstimulate the already activated mTOR, as well as stimulate mast cell and microglia activation and proliferation. The natural flavonoid luteolin inhibits mTOR, mast cells and microglia and could have a significant benefit in ASD.