Neuroinflammation in the pathogenesis of autistic disorder

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Autism is a neurodeveloprmental disorder characterized by poor &vial cognition and, by restricted and stereotyped patterns of behavior and interests, Accumulating evidence suggests that an impaired immunological process may play a role in its pathophysiology Apostmortem brain study of autism has provided evidence showing that an aberrant immunological process (ie., microglial and astroglial activation, and increased proinflammatory cytokines) occurs in the brain regions studied, including the cerebellum, the middle frontal gyrus, and the anterior cingulate gyms. However, it remains to be determined whether microglial activation takes place in the living brain of individuals with autism, and if any the magnitude and extension of microglial 'activation in the brain. Therefore, we detemiined the magnitude and extension of mifroglial activation in brains of persons with autism using (1-(2-chromphynyll-Nanethylpropy1) -3 isoquinoline carboxiunide (111CKR)-PK11195) and PET in vivo. Fifteen d … More rug-naive male subjects with high-functioning (IQ > 70) autism (mean age 22.5 SD 3.0) and 12 healthy male voluntreis (mean age 22.5 SD 1.1) participated in this study. Lb assess the microglial activity DICI(R)-PK11195 binding potential (BP) parametric images were generated ba.axd on a simplified reference tissue model using a normalized mean time activity curve created from the ligand kinetics of the cerebral cortical regions in the control group. The voxel-wi% analyses of fl1C1(R)-PK11195 BP images were conducted using statistical parametric mapping software (SPM2; http: //www.fiLionuclacuk/spm/). In the voxel-based analysis, we hind increased [IIC](R)-PK.11195 binding in the broad brain regions, especially the midbrain, the thalamus, the limbic region (e.g, the anterior cingulate cortex), and the cerebellum in the autistic group compared with the control group. Based on the results of the voxel-based analysis, we restricted the region-of-interest (ROI) analysis to the midbrain, the thalamus, the anterior cingultite cortex, and the cerebellum. The Mann-Whitney U test was used to lest the group differences of [11C](R)-PK11195 BPs between the autistic group and control group in the 4 brain regions. The individuals with autism had signiticantly higher [11C](R)-PK11195BPs than control subjects in the 4 Rols studied: the midbrain (743%, U= 7.0, p <0.001), the thalamus (583%, U=13.0, p <0.001), the anterior cingulate cortex (768%, U= 5.0, p <0.001), and the cerebellum (742%, U= 2.0, p <0.001). Our observation here illu.stnites for the first time that microglial activation cccurs in the broad regions of the living brains of autism. Less