Скачать или смотреть Autism-associated 16p11.2 microdeletion variant impacts: the effects of microbiota disturbances

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Approximately 17% of children are diagnosed with NDDs, including ASD, ADHD, and ID, which are highly heterogenous, frequently co-occur, and manifest in early life in sex-dependent fashion. We speculate that some of this heterogeneity is due to interactions between genetic risk factors and environmental exposures (G x E). During neurodevelopment, both the generation of new neurons, termed neurogenesis, and the gut microbiome are exquisitely sensitive to environmental factors, with recent evidence raising concern about childhood antibiotics. To examine this issue, we designed a new G x E model selecting 16p11.2 microdeletion mouse because this human variant increases ASD risk 38-fold, and exposure to the cephalosporin antibiotic, cefdinir. We assess effects on the gut microbiome, hippocampal neurogenesis and structure, gene expression, serum metabolome, and adult behaviors. Our preliminary results suggest that cefdinir exposure alters all these parameters, supporting a possible role of antibiotic-induced changes of the microbiome in ASD pathogenesis.

Dr. DiCicco-Bloom, M.D. is a Professor of Neuroscience and Cell Biology and Pediatrics (Child Neurology & Neurodevelopmental Disabilities) at Rutgers Robert Wood Johnson Medical School in NJ. He studied at Princeton University, received his M.D. from Cornell University Medical College, and following postdoctoral studies in developmental neuroscience, trained in Pediatrics and Child Neurology at New York Hospital-Cornell Medical Center.

His research seeks to understand the molecular and cellular pathways that regulate the production of neurons (neurogenesis) during brain development, and how genetic and environmental factors disrupt neurogenesis and contribute to neurodevelopmental disorders. Currently, he is exploring how the effects of antibiotics on the gut microbiome and brain development are significantly enhanced in mice that carry a human autism genetic risk variant.
Dr. DiCicco-Bloom has long served scientific and advocacy organizations, setting strategies and priorities for translational research at the NIH, the DOD, and the Society for Neuroscience; at disease organizations including National Alliance for Autism Research, Autism Science Foundation, Autism Speaks, Autism Tissue Program, and is the Scientific Advisor of the Eagles Autism Foundation.