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Cereb Cortex. 2018 Sep 1;28(9):3267-3277. doi: 10.1093/cercor/bhx197.

Cell-Specific Gene-Expression Profiles and Cortical Thickness in the Human Brain.

Author information

1
The Hospital for Sick Children, University of Toronto, Toronto, Canada.
2
Rotman Research Institute, University of Toronto, Toronto, Canada.
3
Centre for Addition and Mental Health, Toronto, Canada.
4
Department of Psychiatry, University of Toronto, Toronto, Canada.
5
Institute of Medical Sciences, University of Toronto, Toronto, Canada.
6
Center for Developing Brain, Child Mind Institute, New York, NY, USA.
7
Montreal Neurological Institute, McGill University, Montreal, Canada.
8
CEGEP Jonquiere, Jonquiere, Canada.
9
Departments of Radiology & Clinical Neuroscience, University of Calgary, Calgary, Canada.
10
Department of Psychology, University of Quebec in Chicoutimi, Chicoutimi, Canada.
11
Department of Psychology, University of Toronto, Toronto,Canada.

Abstract

Neurobiological underpinnings of cortical thickness in the human brain are largely unknown. Here we use cell-type-specific gene markers to evaluate the contribution of 9 neural cell-types in explaining inter-regional variations in cortical thickness and age-related cortical thinning in the adolescent brain. Gene-expression data were derived from the Allen Human Brain Atlas (and validated using the BrainSpan Atlas). Values of cortical thickness/thinning were obtained with magnetic resonance imaging in a sample of 987 adolescents. We show that inter-regional profiles in cortical thickness relate to those in the expression of genes marking CA1 pyramidal cells, astrocytes, and microglia; taken together, the 3 cell types explain 70% of regional variation in cortical thickness. We also show that inter-regional profiles in cortical thinning relate to those in the expression of genes marking CA1 and S1 pyramidal cells, astrocytes and microglia. Using Gene Ontology analysis, we demonstrate that the difference in the contribution of CA1 and S1 pyramidal cells may relate to biological processes such as neuronal plasticity and potassium channel activity, respectively. This "virtual histology" approach (scripts provided) can be used to examine neurobiological underpinnings of cortical profiles associated with development, aging, and various disorders.

PMID:
28968835
DOI:
10.1093/cercor/bhx197
[Indexed for MEDLINE]

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