Focal brain inflammation and autism.
Theoharides, Theoharis C.
Patel, Arti B.
Abstract: 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 ... read moresignificantly 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
Keywords: autism spectrum disorders, blood-brain barrier, brain-derived neurotrophic factor, cerebrospinal fluid, corticotropin-releasing hormone, epigallocatechin gallate, interleukin, monocyte chemotactic protein, mammalian target of rapamycin, mitochondrial, neurotensin, neurotensin receptor, phosphatase and tensin homolog, selective serotonin re-uptake inhibitor, tumor necrosis factor, tuberous sclerosis protein 1 and 2, vascular endothelial growth factor.
Springer Open.read less
- Theoharides, Theoharis, Shahrzad Asadi, and Arti B. Patel. "Focal brain inflammation and autism." Journal of Neuroinflammation 10, no. 1 (12, 2013): 1-7.