Mast cells, microglia and brain inflammation Autism Spectrum Disorders (ASD) are pervasive developmental disorders for which there are no distinct pathogenesis, no biomarkers and few effective treatments.  The diagnosis of ASD has increased more than 10-fold during the last decade to 1/150 children, and more recently to about 1/88 children ( http://www.cdc.gov/Features/CountingAuti\\... ). ASDs involve some immune dysfunction, and  many children with ASD also have atopic features, food allergies and other "allergic-like" symptoms, suggesting mast cell activation by non-allergic triggers. Unique immune cells Mast cells are unique immune cells present in all tissues; they are mostly found in the dienchepalon of the brain that controls emotions. Mast cells act as "alarmins" to environmental, infectious and stress insults. Moreover, children with mastocytosis, a spectrum of diseases that present with gastrointestinal and skin allergies, appear to have a 10-fold higher prevalence of ASD (1/10) than what is reported for the general population. Along with my fellow researchers, I believe that ASD is a neurological disease derived from perinatal auto-immune insults to specific brain areas leading to local encephalopathy. We recently published that neurotensin (NT), a peptide found in the brain and the gut, is increased in the serum of young children with autism. Intestinal mast cells can also be activated by NT, a potent neuropeptide that is abundant in the gut. It is interesting that distribution of NT receptors is more concentrated in the brain diencephalon and the Broca area, which regulates speech, commonly lost or impaired in children with autism. Synergistic