Focal brain inflammation and autism
Abstract (provisional) Full PDF available at link
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. NT stimulates mast cell secretion of mitochondrial DNA that is misconstrued as an innate pathogen triggering an auto-inflammatory response. Lack of the mammalian target of rapamycin (mTOR), which is inhibited by the phosphatase and tensin homolog (PTEN), has been linked to gene mutations associated with higher risk of ASD.
CRH, NT and environmental triggers could hyperstimulate the already activated mTOR leading to higher risk for ASD, 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.
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