24-11-2021

Seminario de Investigación: Clinical correlates of GABAergic interneuron pathology in autism

Verónica Martínez Cerdeño, University of California, Davis & Institute for Regenerative Medicine, Shriners Hospital of Northem California

Resumen: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors. We don't know how specific anatomical alterations contribute to the clinical profile of ASD. We found that parvalbumin-positive Chandelier cells (ChC), a specific type of GABAergic interneuron, are reduced in number in the ASD prefrontal cortex, and assessed the relationship between interneuron pathology with ASD symptoms. We collected clinical records from ASD and control brain donors and characterized GABAergic interneuron pathology in three regions of the prefrontal cortex (BA9, 46, and 47). We assessed the relationship between the severity of core symptoms, as indicated by ADI-R scores, and comorbidities with ChC pathology in ASD. ChC pathological severity in the BA47 (orbitofrontal cortex), as indicated by decreases in PV+ cells and GAT1+ cartridges in two separate cohorts, was significantly correlated with the severity of ASD motor stereotypies. Additionally, ASD subjects with intellectual disability showed a more severe and widespread loss of overall GABAergic interneurons than ASD subjects without intellectual disability.   These data from human subjects indicates that IN pathology is an important contributor to ASD symptomology. These anatomical alterations most likely reflect developmental impairments in proliferation, migration and/or cell death of interneurons. Our findings identify interneuron pathology as an important biomarker for ASD animal model validation, for ASD developmental studies, and for developing targeted therapeutics that are thus far lacking for ASD patients.

Bio: Verónica Martínez Cerdeño received a B.S. in 1998 from Complutense University in Spain. In 2002, received her Ph.D. in Neuroscience under Professor Francisco Clascá at the Autónoma University of Madrid, Spain. She did her postdoctoral training in brain development at Columbia University in New York, in neural stem cells at UCSF in San Francisco, and in autism at the MIND Institute at the UC Davis Medical Center. Currently, she is Professor of Medical Pathology and Laboratory Medicine at the University of California, Davis, and a Faculty at the Institute for Pediatric Regenerative Medicine, the Shriners Hospital of Northern California, and the MIND Institute. She was presented with the prestigious CAMPOS Faculty Scholar Award in 2016, and with the ADVANCE Scholar Award in 2019, in recognition to her teaching, research, and service in her STEM disciplines.

Fecha y Hora: miércoles, 24 de noviembre de 2021, 12: 30 horas

Lugar: Seminario IV

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