Autism-associated 16p11.2 microdeletion impairs prefrontal functional connectivity in mouse and human
| Autor: | Alice Bertero 1, 2, Adam Liska 1, Marco Pagani, 1, Roberta Parolisi 3, Maria Esteban Masferrer 4, Marta Gritti 5, Matteo Pedrazzoli 5, Alberto Galbusera 1, Alessia Sarica 6, Antonio Cerasa 6, 7 Mario Buffelli 8, Raffaella Tonini 5, Annalisa Buffo 3, Cornelius Gross 4, Massimo Pasqualetti 1, Alessandro Gozzi 1 |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Chromosome Disorders Membrane Potentials state Mice 0302 clinical medicine Cognition Copy-number variation Genetic risk Child fMRI DMN resting-state thalamus imaging Mice Knockout medicine.diagnostic_test Functional connectivity Magnetic Resonance Imaging Temporal Lobe Female Chromosome Deletion Adolescent DNA Copy Number Variations Thalamus Prefrontal Cortex Biology resting 03 medical and health sciences Intellectual Disability medicine Animals Humans Cognitive Dysfunction Autistic Disorder Brain function Resting state fMRI medicine.disease Disease Models Animal 030104 developmental biology Neurodevelopmental Disorders Autism Neurology (clinical) Nerve Net Functional magnetic resonance imaging Neuroscience 030217 neurology & neurosurgery Chromosomes Human Pair 16 |
| Zdroj: | Brain (Online) 141 (2018): 2055–2065. doi:10.1093/brain/awy111 info:cnr-pdr/source/autori:Alice Bertero 1,2*, Adam Liska 1*, Marco Pagani,1,* Roberta Parolisi 3, Maria Esteban Masferrer 4, Marta Gritti 5, Matteo Pedrazzoli 5, Alberto Galbusera 1, Alessia Sarica 6, Antonio Cerasa 6,7 Mario Buffelli 8, Raffaella Tonini 5, Annalisa Buffo 3, Cornelius Gross 4, Massimo Pasqualetti 1,2 and Alessandro Gozzi 1/titolo:Autism-associated 16p11.2 microdeletion impairs prefrontal functional connectivity in mouse and human/doi:10.1093%2Fbrain%2Fawy111/rivista:Brain (Online)/anno:2018/pagina_da:2055/pagina_a:2065/intervallo_pagine:2055–2065/volume:141 |
| ISSN: | 1460-2156 |
| DOI: | 10.1093/brain/awy111 |
| Popis: | Human genetic studies are rapidly identifying variants that increase risk for neurodevelopmental disorders. However, it remains unclear how specific mutations impact brain function and contribute to neuropsychiatric risk. Chromosome 16p11.2 deletion is one of the most common copy number variations in autism and related neurodevelopmental disorders. Using resting state functional MRI data from the Simons Variation in Individuals Project (VIP) database, we show that 16p11.2 deletion carriers exhibit impaired prefrontal connectivity, resulting in weaker long-range functional coupling with temporal-parietal regions. These functional changes are associated with socio-cognitive impairments. We also document that a mouse with the same genetic deficiency exhibits similarly diminished prefrontal connectivity, together with thalamo-prefrontal miswiring and reduced long-range functional synchronization. These results reveal a mechanistic link between specific genetic risk for neurodevelopmental disorders and long-range functional coupling, and suggest that deletion in 16p11.2 may lead to impaired socio-cognitive function via dysregulation of prefrontal connectivity. |
| Databáze: | OpenAIRE |
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