Mast cells, brain inflammation and autism.
Increasing evidence indicates that brain inflammation is involved in the pathogenesis of neuropsychiatric diseases. Mast cells (MCs) are located perivascularly close to neurons and microglia, primarily in the leptomeninges, thalamus, hypothalamus and especially the median eminence. Corticotropin-releasing factor (CRF) is secreted from the hypothalamus under stress and, together with neurotensin (NT), can stimulate brain MCs to release inflammatory and neurotoxic mediators that disrupt the blood-brain barrier (BBB), stimulate microglia and cause focal inflammation. CRF and NT synergistically stimulate MCs and increase vascular permeability; these peptides can also induce each other׳s surface receptors on MCs leading to autocrine and paracrine effects. As a result, brain MCs may be involved in the pathogenesis of "brain fog," headaches, and autism spectrum disorders (ASDs), which worsen with stress. CRF and NT are significantly increased in serum of ASD children compared to normotypic controls further strengthening their role in the pathogenesis of autism. There are no clinically affective treatments for the core symptoms of ASDs, but pilot clinical trials using natural-antioxidant and anti-inflammatory molecules reported statistically significant benefit.
Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, USA; Department of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA; Department of Psychiatry, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA. Electronic address: theoharis.theoharides@tufts.edu.
Theoharis C
TC
Theoharides
Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, USA.
Julia M
JM
Stewart
Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, USA.
Smaro
S
Panagiotidou
IMMUNOe, Centennial, CO, USA.
Isaac
I
Melamed
D000818:Animals; D001321:Autistic Disorder / Q000150:complications* / Q000276:immunology*; D004660:Encephalitis / Q000150:complications*; D006261:Headache / Q000150:complications; D006801:Humans; D008407:Mast Cells / Q000473:pathology*
Autism; Brain; Headache; Inflammation; Mast cells; Mastocytosis