AUTHOR=Brandenburg Cheryl , Griswold Anthony J. , Van Booven Derek J. , Kilander Michaela B. C. , Frei Jeannine A. , Nestor Michael W. , Dykxhoorn Derek M. , Pericak-Vance Margaret A. , Blatt Gene J. TITLE=Transcriptomic analysis of isolated and pooled human postmortem cerebellar Purkinje cells in autism spectrum disorders JOURNAL=Frontiers in Genetics VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.944837 DOI=10.3389/fgene.2022.944837 ISSN=1664-8021 ABSTRACT=

At present, the neuronal mechanisms underlying the diagnosis of autism spectrum disorder (ASD) have not been established. However, studies from human postmortem ASD brains have consistently revealed disruptions in cerebellar circuitry, specifically reductions in Purkinje cell (PC) number and size. Alterations in cerebellar circuitry would have important implications for information processing within the cerebellum and affect a wide range of human motor and non-motor behaviors. Laser capture microdissection was performed to obtain pure PC populations from a cohort of postmortem control and ASD cases and transcriptional profiles were compared. The 427 differentially expressed genes were enriched for gene ontology biological processes related to developmental organization/connectivity, extracellular matrix organization, calcium ion response, immune function and PC signaling alterations. Given the complexity of PCs and their far-ranging roles in response to sensory stimuli and motor function regulation, understanding transcriptional differences in this subset of cerebellar cells in ASD may inform on convergent pathways that impact neuronal function.