Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia

Arnsten, Amy F.T.; Woo, Elizabeth; Yang, Shengtao; Wang, Min; Datta, Dibyadeep

doi:10.1016/j.biopsych.2022.02.003

Cited by 23 publications

(16 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such enhanced gene expression patterns are also observed in other DLPFC slices, for example, slice 151507 ( Fig. 6c ), where RELN 40 (logFC = 3.24) and ADCYAP1 41 (logFC=2.81), i.e. makers of Layer 1 and Layer 2, present remarkable enhancement, in contrast to their sporadic expressions in raw data.…”

Section: Resultssupporting

confidence: 58%

SiGra: Single-cell spatial elucidation through image-augmented graph transformer

Tang

Zhang

Yang

et al. 2022

Preprint

View full text Add to dashboard Cite

The recent advances in high throughput molecular imaging push the spatial transcriptomics technologies to the subcellular resolution, which breaks the limitations of both single cell RNA seq and array based spatial profiling. The latest released single cell spatial transcriptomics data from NanoString CosMx and MERSCOPE platforms contains multi channel immunohistochemistry images with rich information of cell types, functions, and morphologies of cellular compartments. In this work, we developed a novel method, Single cell spatial elucidation through image augmented Graph transformer (SiGra), to reveal spatial domains and enhance the substantially sparse and noisy transcriptomics data. SiGra applies hybrid graph transformers over a spatial graph that comprises high-content images and gene expressions of individual cells. SiGra outperformed state of the art methods on both single cell spatial profiles and spot level spatial transcriptomics data from complex tissues. The inclusion of immunohistochemistry images improved the model performance by 37% (95%CI: 27% to 50%). SiGra improves the characterization of intratumor heterogeneity and intercellular communications in human lung cancer samples, meanwhile recovers the known microscopic anatomy in both human brain and mouse liver tissues. Overall, SiGra effectively integrates different spatial modality data to gain deep insights into the spatial cellular ecosystems.

show abstract

Section: Resultssupporting

confidence: 58%

SiGra: Single-cell spatial elucidation through image-augmented graph transformer

Tang

Zhang

Yang

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…It is also well documented that the expression of risk genes for SCZ is enriched in the prefrontal cortex compared to other brain areas. Structural and functional neuroimaging studies in populations with SCZ have revealed dysfunction of the DLPFC [16]. Given this evidence, aberrant rDNA content in the DLPFC of patients with SCZ, as shown in this study, may play an important role in DLPFC volume and functional abnormalities through dysfunctional neural plasticity caused by rDNA transcriptional activity.…”

Section: Plos Onesupporting

confidence: 55%

Ribosomal DNA gene copies are increased in blood and brain of Japanese schizophrenia patients

Otsuka

Tanifuji

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

Past evidence has indicated increased ribosomal DNA (rDNA) content in the blood of patients with schizophrenia (SCZ) among European populations. Here, for the first time, we investigated the rDNA copy number (rDNAcn) of SCZ in East Asian populations as well as in blood and brain tissues. In this study, we measured 18S/28S rDNAcn in the peripheral blood of live participants (81 patients with SCZ and 98 healthy controls) and the dorsolateral prefrontal cortices (DLPFCs) of postmortem individuals (10 patients with SCZ and 23 non-psychiatric controls) in the Japanese population. Patients with SCZ had significantly increased 18S/28S rDNAcn in the blood compared to controls (p < 0.05). 18S rDNAcn was significantly increased in the brain of patients with SCZ compared to controls (p < 0.05). In conclusion, regarding the increased rDNAcn in the blood of patients with SCZ that was previously reported in Europeans, we successfully replicated this by using a different, ethnically East Asian, cohort. Additionally, we provide the first evidence of increased rDNAcn in the brain of patients with SCZ. These findings may help to elucidate the molecular underpinnings of SCZ pathophysiology related to ribosomal DNA abnormalities.

show abstract

“…They provide a profound cytoarchitectonic basis that will be complemented by future mapping studies like analyses of receptor or myelin architecture. The specific cytoarchitectonic characteristics of the new delineated areas may help further investigate laminar-specific differences as observed in layer III, especially in the context of schizophrenia (Arnsten et al, 2022 ). Furthermore, the new maps are linked to toolboxes (i.e., “siibra toolsuite” Dickscheid, 2021 ) that enable, for example, comparison with neuroimaging data.…”

Section: Discussionmentioning

confidence: 99%

Cytoarchitecture, intersubject variability, and 3D mapping of four new areas of the human anterior prefrontal cortex

et al. 2022

View full text Add to dashboard Cite

The dorsolateral prefrontal cortex (DLPFC) plays a key role in cognitive control and executive functions, including working memory, attention, value encoding, decision making, monitoring, and controlling behavioral strategies. However, the relationships between this variety of functions and the underlying cortical areas, which specifically contribute to these functions, are not yet well-understood. Existing microstructural maps differ in the number, localization, and extent of areas of the DLPFC. Moreover, there is a considerable intersubject variability both in the sulcal pattern and in the microstructure of this region, which impedes comparison with functional neuroimaging studies. The aim of this study was to provide microstructural, cytoarchitectonic maps of the human anterior DLPFC in 3D space. Therefore, we analyzed 10 human post-mortem brains and mapped their borders using a well-established approach based on statistical image analysis. Four new areas (i.e., SFS1, SFS2, MFG1, and MFG2) were identified in serial, cell-body stained brain sections that occupy the anterior superior frontal sulcus and middle frontal gyrus, i.e., a region corresponding to parts of Brodmann areas 9 and 46. Differences between areas in cytoarchitecture were captured using gray level index profiles, reflecting changes in the volume fraction of cell bodies from the surface of the brain to the cortex-white matter border. A hierarchical cluster analysis of these profiles indicated that areas of the anterior DLPFC displayed higher cytoarchitectonic similarity between each other than to areas of the neighboring frontal pole (areas Fp1 and Fp2), Broca's region (areas 44 and 45) of the ventral prefrontal cortex, and posterior DLPFC areas (8d1, 8d2, 8v1, and 8v2). Area-specific, cytoarchitectonic differences were found between the brains of males and females. The individual areas were 3D-reconstructed, and probability maps were created in the MNI Colin27 and ICBM152casym reference spaces to take the variability of areas in stereotaxic space into account. The new maps contribute to Julich-Brain and are publicly available as a resource for studying neuroimaging data, helping to clarify the functional and organizational principles of the human prefrontal cortex.

show abstract

Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia

Cited by 23 publications

References 125 publications

SiGra: Single-cell spatial elucidation through image-augmented graph transformer

SiGra: Single-cell spatial elucidation through image-augmented graph transformer

Ribosomal DNA gene copies are increased in blood and brain of Japanese schizophrenia patients

Cytoarchitecture, intersubject variability, and 3D mapping of four new areas of the human anterior prefrontal cortex

Contact Info

Product

Resources

About