Comparing the Expression of Genes Related to Serotonin (5-HT) in C57BL/6J Mice and Humans Based on Data Available at the Allen Mouse Brain Atlas and Allen Human Brain Atlas

Abstract

Brain atlases are tools based on comprehensive studies used to locate biological characteristics (structures, connections, proteins, and gene expression) in different regions of the brain. These atlases have been disseminated to the point where tools have been created to store, manage, and share the information they contain. This study used the data published by the Allen Mouse Brain Atlas (2004) for mice (C57BL/6J) and Allen Human Brain Atlas (2010) for humans (6 donors) to compare the expression of serotonin-related genes. Genes of interest were searched for manually in each case (in situ hybridization for mice and microarrays for humans), normalized expression data (z-scores) were extracted, and the results were graphed. Despite the differences in methodology, quantification, and subjects used in the process, a high degree of similarity was found between expression data. Here we compare expression in a way that allows the use of translational research methods to infer and validate knowledge. This type of study allows part of the relationship between structures and functions to be identified, by examining expression patterns and comparing levels of expression in different states, anatomical correlations, and phenotypes between different species. The study concludes by discussing the importance of knowing, managing, and disseminating comprehensive, open-access studies in neuroscience.

A practical guide to linking brain-wide gene expression and neuroimaging data

“…Many analyses interested in transcriptomic signatures of IDPs will be primarily interested in these brain-specific genes. Various methods for pre-selecting genes of interest have been adopted, including selecting: (i) disease-specific genes (Rittman et al, 2016, Romme et al, 2017, Yokoyama et al, 2017, (ii) genes related to a priori hypotheses (Goyal et al, 2014, Komorowski et al, 2016, Krienen et al, 2016, Acevedo-Triana et al, 2017, or (iii) genes that are expressed consistently across all six AHBA brains, as quantified using the DS measure (Hawrylycz et al, 2015). Genes with high DS values demonstrate consistent patterns of regional variation in expression across the six AHBA subjects, and have been shown to be enriched for brain-related biological function (Hawrylycz et al, 2015).…”

“…Filtering based on DS thus offers a more targeted approach for investigating relationships between IDPs and gene expression compared to the whole-genome analysis. The selection of disease-specific genes is traditionally based on previous GWAS studies (Satake et al, 2009, Simón-Sánchez et al, 2009, Höglinger et al, 2011, Ferrari et al, 2014, Ripke et al, 2014, Kouri et al, 2015, while gene selection based on an a priori hypothesis can depend on other factors such as a specific involvement in clinical disorders (Komorowski et al, 2016, Acevedo-Triana et al, 2017. One particular set of 19 genes demonstrating a selective enrichment in the upper layers of the human cortex compared to mouse [Human Supragranular Enriched (HSE) genes] has been extensively investigated and was found to be implicated in both the functional (Krienen et al, 2016) and topological organisation of the brain (Vértes et al, 2016, Romero-Garcia et al, 2018b.…”

A practical guide to linking brain-wide gene expression and neuroimaging data

“…Many analyses interested in transcriptomic signatures of IDPs will be primarily interested in these brain-specific genes. Various methods for pre-selecting genes of interest have been adopted, including selecting: (i) disease-specific genes , Romme et al, 2017, Yokoyama et al, 2017, (ii) genes related to a priori hypotheses (Goyal et al, 2014, Komorowski et al, 2016, Krienen et al, 2016, Acevedo-Triana et al, 2017 genes that are expressed consistently across all six AHBA brains, as quantified using the DS measure (Hawrylycz et al, 2015). Genes with high DS values demonstrate consistent patterns of regional variation in expression across the six AHBA subjects, and have been shown to be enriched for brain-related biological function (Hawrylycz et al, 2015).…”

“…Filtering based on DS thus offers a more targeted approach for investigating relationships between IDPs and gene expression compared to the whole-genome analysis. The selection of disease-specific genes is traditionally based on previous GWAS studies (Satake et al, 2009, Simón-Sánchez et al, 2009, Höglinger et al, 2011, Ferrari et al, 2014, Ripke et al, 2014, Kouri et al, 2015, while gene selection based on an a priori hypothesis can depend on other factors such as a specific involvement in clinical disorders (Komorowski et al, 2016, Acevedo-Triana et al, 2017. One particular set of 19 genes demonstrating a selective enrichment in the upper layers of the human cortex compared to mouse [Human Supragranular Enriched (HSE) genes] has been extensively investigated and was found to be implicated in both the functional (Krienen et al, 2016) and topological organisation of the brain , Romero-Garcia et al, 2018b.…”

Mismatch negativity as an index of target engagement for excitation/inhibition-based treatment development: a double-blind, placebo-controlled, randomized, single-dose cross-over study of the serotonin type-3 receptor antagonist CVN058

“…5-HT 3 R are relatively concentrated in areas important for cognition, including the auditory cortex, hippocampus, and amygdala [29][30][31]. Preclinically, 5-HT 3 R antagonists attenuate neurocognitive effects induced by NMDAR antagonists such as PCP [32] or MK-801 [33] and may also modulate glutamatergic neurotransmission via 5-HT 3 R expressed on GABAergic VIP/CCK interneurons [22,[34][35][36].…”