Article (Scientific journals)
Altered Neocortical Gene Expression, Brain Overgrowth and Functional Over-Connectivity in Chd8 Haploinsufficient Mice.
Suetterlin, Philipp; Hurley, Shaun; Mohan, Conor et al.
2018In Cerebral Cortex, 28 (6), p. 2192-2206
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Abstract :
[en] Truncating CHD8 mutations are amongst the highest confidence risk factors for autism spectrum disorder (ASD) identified to date. Here, we report that Chd8 heterozygous mice display increased brain size, motor delay, hypertelorism, pronounced hypoactivity, and anomalous responses to social stimuli. Whereas gene expression in the neocortex is only mildly affected at midgestation, over 600 genes are differentially expressed in the early postnatal neocortex. Genes involved in cell adhesion and axon guidance are particularly prominent amongst the downregulated transcripts. Resting-state functional MRI identified increased synchronized activity in cortico-hippocampal and auditory-parietal networks in Chd8 heterozygous mutant mice, implicating altered connectivity as a potential mechanism underlying the behavioral phenotypes. Together, these data suggest that altered brain growth and diminished expression of important neurodevelopmental genes that regulate long-range brain wiring are followed by distinctive anomalies in functional brain connectivity in Chd8+/- mice. Human imaging studies have reported altered functional connectivity in ASD patients, with long-range under-connectivity seemingly more frequent. Our data suggest that CHD8 haploinsufficiency represents a specific subtype of ASD where neuropsychiatric symptoms are underpinned by long-range over-connectivity.
Disciplines :
Neurosciences & behavior
Author, co-author :
Suetterlin, Philipp
Hurley, Shaun
Mohan, Conor
Riegman, Kimberley L. H.
Pagani, Marco
Caruso, Angela
Ellegood, Jacob
Galbusera, Alberto
Crespo-Enriquez, Ivan
Michetti, Caterina
Yee, Yohan
Ellingford, Robert
Brock, Olivier ;  Université de Liège - ULiège
Delogu, Alessio
Francis-West, Philippa
Lerch, Jason P.
Scattoni, Maria Luisa
Gozzi, Alessandro
Fernandes, Cathy
Basson, M. Albert
More authors (10 more) Less
Language :
English
Title :
Altered Neocortical Gene Expression, Brain Overgrowth and Functional Over-Connectivity in Chd8 Haploinsufficient Mice.
Publication date :
2018
Journal title :
Cerebral Cortex
ISSN :
1047-3211
eISSN :
1460-2199
Publisher :
Oxford University Press, United Kingdom
Volume :
28
Issue :
6
Pages :
2192-2206
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 17 January 2019

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