Abstract

Brodmann Area 46 (BA46) has long been regarded as a hotspot of disease pathology in individuals with schizophrenia (SCH) and major depressive disorder (MDD). Pyramidal neurons in layer III of the Brodmann Area 46 (BA46) project to other cortical regions and play a fundamental role in corticocortical and thalamocortical circuits. The AutoCUTS-LM pipeline was used to study the 3-dimensional structural morphology and spatial organization of pyramidal cells. Using quantitative light microscopy, we used stereology to calculate the entire volume of layer III in BA46 and the total number and density of pyramidal cells. Volume tensors estimated by the planar rotator quantified the volume, shape, and nucleus displacement of pyramidal cells. All of these assessments were carried out in four groups of subjects: controls (C, n = 10), SCH (n = 10), MDD (n = 8), and suicide subjects with a history of depression (SU, n = 11). SCH subjects had a significantly lower somal volume, total number, and density of pyramidal neurons when compared to C and tended to show a volume reduction in layer III of BA46. When comparing MDD subjects with C, the measured parameters were inclined to follow SCH, although there was only a significant reduction in pyramidal total cell number. While no morphometric differences were observed between SU and MDD, SU had a significantly higher total number of pyramidal cells and nucleus displacement than SCH. Finally, no differences in the spatial organization of pyramidal cells were found among groups. These results suggest that despite significant morphological alterations in layer III of BA46, which may impair prefrontal connections in people with SCH and MDD, the spatial organization of pyramidal cells remains the same across the four groups and suggests no defects in neuronal migration. The increased understanding of pyramidal cell biology may provide the cellular basis for symptoms and neuroimaging observations in SCH and MDD patients.

Details

Title
Layer III pyramidal cells in the prefrontal cortex reveal morphological changes in subjects with depression, schizophrenia, and suicide
Author
Larsen, Nick Y. 1   VIAFID ORCID Logo  ; Vihrs, Ninna 2 ; Møller, Jesper 3 ; Sporring, Jon 4 ; Tan, Xueke 5 ; Li, Xixia 6 ; Ji, Gang 6 ; Rajkowska, Grazyna 7   VIAFID ORCID Logo  ; Sun, Fei 8 ; Nyengaard, Jens R. 9 

 Aarhus University, Core Centre for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Aarhus University, Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Sino-Danish Center for Education and Research, Aarhus, Denmark (GRID:grid.7048.b); University of the Chinese Academy of Sciences, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419); Aalborg University, Aarhus University and University of Copenhagen, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus, Denmark (GRID:grid.5117.2) (ISNI:0000 0001 0742 471X) 
 Aalborg University, Department of Mathematical Sciences, Aalborg, Denmark (GRID:grid.5117.2) (ISNI:0000 0001 0742 471X) 
 Aalborg University, Aarhus University and University of Copenhagen, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus, Denmark (GRID:grid.5117.2) (ISNI:0000 0001 0742 471X); Aalborg University, Department of Mathematical Sciences, Aalborg, Denmark (GRID:grid.5117.2) (ISNI:0000 0001 0742 471X) 
 Aalborg University, Aarhus University and University of Copenhagen, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus, Denmark (GRID:grid.5117.2) (ISNI:0000 0001 0742 471X); University of Copenhagen, Department of Computer Science, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X) 
 CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, National Key Laboratory of Biomacromolecules, Beijing, China (GRID:grid.418856.6) (ISNI:0000 0004 1792 5640); Institute of Biophysics, Chinese Academy of Sciences, Center for Biological Imaging, Beijing, China (GRID:grid.418856.6) (ISNI:0000 0004 1792 5640) 
 University of Copenhagen, Department of Computer Science, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X); CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, National Key Laboratory of Biomacromolecules, Beijing, China (GRID:grid.418856.6) (ISNI:0000 0004 1792 5640) 
 University of Mississippi Medical Center, Department of Psychiatry and Human Behavior, Jackson, USA (GRID:grid.410721.1) (ISNI:0000 0004 1937 0407) 
 Sino-Danish Center for Education and Research, Aarhus, Denmark (GRID:grid.410721.1); University of the Chinese Academy of Sciences, Beijing, China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419); CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, National Key Laboratory of Biomacromolecules, Beijing, China (GRID:grid.418856.6) (ISNI:0000 0004 1792 5640); Institute of Biophysics, Chinese Academy of Sciences, Center for Biological Imaging, Beijing, China (GRID:grid.418856.6) (ISNI:0000 0004 1792 5640) 
 Aarhus University, Core Centre for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Sino-Danish Center for Education and Research, Aarhus, Denmark (GRID:grid.7048.b); Aalborg University, Aarhus University and University of Copenhagen, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus, Denmark (GRID:grid.5117.2) (ISNI:0000 0001 0742 471X); Aarhus University Hospital, Department of Pathology, Aarhus, Denmark (GRID:grid.154185.c) (ISNI:0000 0004 0512 597X) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
21583188
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2709801635
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.