Transcriptional Analysis of Cytokines in the Cerebral Cortex of Autistic Patients

Background: Autism is an idiopathic pervasive neurodevelopmental disorder associated with an altered immunological response evidenced by a neuroinflammatory process in the CNS of autistic individuals. Cytokines are involved in the regulation of inflammatory responses, and increased levels of certain cytokines have been demonstrated in the sera, cerebrospinal fluid, peripheral blood mononuclear cells and brain tissue in patients with autism spectrum disorder (ASD). Genotypic analyses of polymorphic sites in some cytokine genes of autistic individuals have yielded significant results, but the picture is still incomplete. Cytokine transcriptional analyses in autism should provide a better understanding of the potential role of the immune system in this disease. Objectives: The main objective of the current study was to perform transcriptional profiling of a panel of cytokine and chemokine genes in different regions of post-mortem brain tissues of autistic subjects and controls. Methods: Post-mortem brain tissue samples were provided by the Autism Tissue Program. After RNA extraction, transcriptional profiling was performed by reverse transcription - real time PCR in 5 cortical regions: BA 4, 9, 17, 22 and 46. Results: Preliminary analysis revealed that cytokine (TNFα, IL-6, TGFβ1), and chemokine (IL-8) transcripts were increased in all brain regions (especially BA 46, dorsolateral prefrontal cortex) except BA 22 (superior temporal gyrus/Wernicke's area) in autism as compared with controls. Conclusions: This study reveals an up-regulation of cytokine and chemokine expression in autism in many cortical regions. We plan to expand the cytokine and chemokine panel and the sample size; but the current data suggest a heterogeneous regulation of cytokine gene transcription in autistic brains, where different brain regions show a differential inflammatory response.