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Allen human brain atlas

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https://www.readbyqxmd.com/read/28515688/insulin-resistance-as-a-link-between-amyloid-beta-and-tau-pathologies-in-alzheimer-s-disease
#1
Roger J Mullins, Thomas C Diehl, Chee W Chia, Dimitrios Kapogiannis
Current hypotheses and theories regarding the pathogenesis of Alzheimer's disease (AD) heavily implicate brain insulin resistance (IR) as a key factor. Despite the many well-validated metrics for systemic IR, the absence of biomarkers for brain-specific IR represents a translational gap that has hindered its study in living humans. In our lab, we have been working to develop biomarkers that reflect the common mechanisms of brain IR and AD that may be used to follow their engagement by experimental treatments...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28461466/oxytocin-under-opioid-antagonism-leads-to-supralinear-enhancement-of-social-attention
#2
Olga Dal Monte, Matthew Piva, Kevin M Anderson, Marios Tringides, Avram J Holmes, Steve W C Chang
To provide new preclinical evidence toward improving the efficacy of oxytocin (OT) in treating social dysfunction, we tested the benefit of administering OT under simultaneously induced opioid antagonism during dyadic gaze interactions in monkeys. OT coadministered with a μ-opioid receptor antagonist, naloxone, invoked a supralinear enhancement of prolonged and selective social attention, producing a stronger effect than the summed effects of each administered separately. These effects were consistently observed when averaging over entire sessions, as well as specifically following events of particular social importance, including mutual eye contact and mutual reward receipt...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28420888/global-gene-expression-profiling-of-healthy-human-brain-and-its-application-in-studying-neurological-disorders
#3
Simarjeet K Negi, Chittibabu Guda
Brain function is governed by precise regulation of gene expression across its anatomically distinct structures; however, the expression patterns of genes across hundreds of brain structures are not clearly understood. Here, we describe a gene expression model, which is representative of the healthy human brain transcriptome by using data from the Allen Brain Atlas. Our in-depth gene expression profiling revealed that 84% of genes are expressed in at least one of the 190 brain structures studied. Hierarchical clustering based on gene expression profiles delineated brain regions into structurally tiered spatial groups and we observed striking enrichment for region-specific processes...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28334178/inter-regional-variations-in-gene-expression-and-age-related-cortical-thinning-in-the-adolescent-brain
#4
Angelita Pui-Yee Wong, Leon French, Gabriel Leonard, Michel Perron, G Bruce Pike, Louis Richer, Suzanne Veillette, Zdenka Pausova, Tomáš Paus
Age-related decreases in cortical thickness observed during adolescence may be related to fluctuations in sex and stress hormones. We examine this possibility by relating inter-regional variations in age-related cortical thinning (data from the Saguenay Youth Study) to inter-regional variations in expression levels of relevant genes (data from the Allen Human Brain Atlas); we focus on genes coding for glucocorticoid receptor (NR3C1), androgen receptor (AR), progesterone receptor (PGR), and estrogen receptors (ESR1 and ESR2)...
February 25, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28321948/gene-networks-show-associations-with-seed-region-connectivity
#5
Marie Forest, Yasser Iturria-Medina, Jennifer S Goldman, Claudia L Kleinman, Amanda Lovato, Kathleen Oros Klein, Alan Evans, Antonio Ciampi, Aurélie Labbe, Celia M T Greenwood
Primary patterns in adult brain connectivity are established during development by coordinated networks of transiently expressed genes; however, neural networks remain malleable throughout life. The present study hypothesizes that structural connectivity from key seed regions may induce effects on their connected targets, which are reflected in gene expression at those targeted regions. To test this hypothesis, analyses were performed on data from two brains from the Allen Human Brain Atlas, for which both gene expression and DW-MRI were available...
June 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28320311/a-receptor-based-analysis-of-local-ecosystems-in-the-human-brain
#6
Skirmantas Janušonis
BACKGROUND: As a complex system, the brain is a self-organizing entity that depends on local interactions among cells. Its regions (anatomically defined nuclei and areas) can be conceptualized as cellular ecosystems, but the similarity of their functional profiles is poorly understood. The study used the Allen Human Brain Atlas to classify 169 brain regions into hierarchically-organized environments based on their expression of 100 G protein-coupled neurotransmitter receptors, with no a priori reference to the regions' positions in the brain's anatomy or function...
March 20, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28221363/premature-primary-tooth-eruption-in-cognitive-motor-delayed-adnp-mutated-children
#7
I Gozes, A Van Dijck, G Hacohen-Kleiman, I Grigg, G Karmon, E Giladi, M Eger, Y Gabet, M Pasmanik-Chor, E Cappuyns, O Elpeleg, R F Kooy, S Bedrosian-Sermone
A major flaw in autism spectrum disorder (ASD) management is late diagnosis. Activity-dependent neuroprotective protein (ADNP) is a most frequent de novo mutated ASD-related gene. Functionally, ADNP protects nerve cells against electrical blockade. In mice, complete Adnp deficiency results in dysregulation of over 400 genes and failure to form a brain. Adnp haploinsufficiency results in cognitive and social deficiencies coupled to sex- and age-dependent deficits in the key microtubule and ion channel pathways...
February 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28132031/brainscope-interactive-visual-exploration-of-the-spatial-and-temporal-human-brain-transcriptome
#8
Sjoerd M H Huisman, Baldur van Lew, Ahmed Mahfouz, Nicola Pezzotti, Thomas Höllt, Lieke Michielsen, Anna Vilanova, Marcel J T Reinders, Boudewijn P F Lelieveldt
Spatial and temporal brain transcriptomics has recently emerged as an invaluable data source for molecular neuroscience. The complexity of such data poses considerable challenges for analysis and visualization. We present BrainScope: a web portal for fast, interactive visual exploration of the Allen Atlases of the adult and developing human brain transcriptome. Through a novel methodology to explore high-dimensional data (dual t-SNE), BrainScope enables the linked, all-in-one visualization of genes and samples across the whole brain and genome, and across developmental stages...
January 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28105773/exosomal-biomarkers-of-brain-insulin-resistance-associated-with-regional-atrophy-in-alzheimer-s-disease
#9
Roger J Mullins, Maja Mustapic, Edward J Goetzl, Dimitrios Kapogiannis
Brain insulin resistance (IR), which depends on insulin-receptor-substrate-1 (IRS-1) phosphorylation, is characteristic of Alzheimer's disease (AD). Previously, we demonstrated higher pSer312-IRS-1 (ineffective insulin signaling) and lower p-panTyr-IRS-1 (effective insulin signaling) in neural origin-enriched plasma exosomes of AD patients vs. CONTROLS: Here, we hypothesized that these exosomal biomarkers associate with brain atrophy in AD. We studied 24 subjects with biomarker-supported probable AD (low CSF Aβ42 )...
April 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28053035/a-high-resolution-in-vivo-atlas-of-the-human-brain-s-serotonin-system
#10
Vincent Beliveau, Melanie Ganz, Ling Feng, Brice Ozenne, Liselotte Højgaard, Patrick M Fisher, Claus Svarer, Douglas N Greve, Gitte M Knudsen
The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4) and the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of positron emission tomography (PET) and magnetic resonance imaging (MRI) scans acquired in a total of 210 healthy individuals...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28034760/insulin-resistance-in-alzheimer-s-disease
#11
REVIEW
Thomas Diehl, Roger Mullins, Dimitrios Kapogiannis
The links between systemic insulin resistance (IR), brain-specific IR, and Alzheimer's disease (AD) have been an extremely productive area of current research. This review will cover the fundamentals and pathways leading to IR, its connection to AD via cellular mechanisms, the most prominent methods and models used to examine it, an introduction to the role of extracellular vesicles (EVs) as a source of biomarkers for IR and AD, and an overview of modern clinical studies on the subject. To provide additional context, we also present a novel analysis of the spatial correlation of gene expression in the brain with the aid of Allen Human Brain Atlas data...
May 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28018170/mrna-transcriptomics-of-galectins-unveils-heterogeneous-organization-in-mouse-and-human-brain
#12
Sebastian John, Rashmi Mishra
Background: Galectins, a family of non-classically secreted, β-galactoside binding proteins is involved in several brain disorders; however, no systematic knowledge on the normal neuroanatomical distribution and functions of galectins exits. Hence, the major purpose of this study was to understand spatial distribution and predict functions of galectins in brain and also compare the degree of conservation vs. divergence between mouse and human species. The latter objective was required to determine the relevance and appropriateness of studying galectins in mouse brain which may ultimately enable us to extrapolate the findings to human brain physiology and pathologies...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27913432/von-economo-neurons-and-fork-cells-a-neurochemical-signature-linked-to-monoaminergic-function
#13
Anke A Dijkstra, Li-Chun Lin, Alissa L Nana, Stephanie E Gaus, William W Seeley
The human anterior cingulate and frontoinsular cortices are distinguished by 2 unique Layer 5 neuronal morphotypes, the von Economo neurons (VENs) and fork cells, whose biological identity remains mysterious. Insights could impact research on diverse neuropsychiatric diseases to which these cells have been linked. Here, we leveraged the Allen Brain Atlas to evaluate mRNA expression of 176 neurotransmitter-related genes and identified vesicular monoamine transporter 2 (VMAT2), gamma-aminobutyric acid (GABA) receptor subunit θ (GABRQ), and adrenoreceptor α-1A (ADRA1A) expression in human VENs, fork cells, and a minority of neighboring Layer 5 neurons...
December 1, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27909009/association-of-protein-distribution-and-gene-expression-revealed-by-pet-and-post-mortem-quantification-in-the-serotonergic-system-of-the-human-brain
#14
A Komorowski, G M James, C Philippe, G Gryglewski, A Bauer, M Hienert, M Spies, A Kautzky, T Vanicek, A Hahn, T Traub-Weidinger, D Winkler, W Wadsak, M Mitterhauser, M Hacker, S Kasper, R Lanzenberger
Regional differences in posttranscriptional mechanisms may influence in vivo protein densities. The association of positron emission tomography (PET) imaging data from 112 healthy controls and gene expression values from the Allen Human Brain Atlas, based on post-mortem brains, was investigated for key serotonergic proteins. PET binding values and gene expression intensities were correlated for the main inhibitory (5-HT1A) and excitatory (5-HT2A) serotonin receptor, the serotonin transporter (SERT) as well as monoamine oxidase-A (MAO-A), using Spearman's correlation coefficients (rs) in a voxel-wise and region-wise analysis...
January 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/27896963/exploring-brain-transcriptomic-patterns-a-topological-analysis-using-spatial-expression-networks
#15
Zhana Kuncheva, Michelle L Krishnan, Giovanni Montana
Characterizing the transcriptome architecture of the human brain is fundamental in gaining an understanding of brain function and disease. A number of recent studies have investigated patterns of brain gene expression obtained from an extensive anatomical coverage across the entire human brain using experimental data generated by the Allen Human Brain Atlas (AHBA) project. In this paper, we propose a new representation of a gene's transcription activity that explicitly captures the pattern of spatial co-expression across different anatomical brain regions...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27856786/a-high-resolution-in-vivo-atlas-of-the-human-brain-s-serotonin-system
#16
Vincent Beliveau, Melanie Ganz, Ling Feng, Brice Ozenne, Liselotte Højgaard, Patrick M Fisher, Claus Svarer, Douglas N Greve, Gitte M Knudsen
The serotonin (5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. We here present a high-resolution multi-dimensional in vivo atlas of four of the human brain's 5-HT receptors (5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4) as well as of the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) scans, acquired in a total of 210 healthy individuals...
November 17, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27747820/two-dimensional-enrichment-analysis-for-mining-high-level-imaging-genetic-associations
#17
Xiaohui Yao, Jingwen Yan, Sungeun Kim, Kwangsik Nho, Shannon L Risacher, Mark Inlow, Jason H Moore, Andrew J Saykin, Li Shen
Enrichment analysis has been widely applied in the genome-wide association studies, where gene sets corresponding to biological pathways are examined for significant associations with a phenotype to help increase statistical power and improve biological interpretation. In this work, we expand the scope of enrichment analysis into brain imaging genetics, an emerging field that studies how genetic variation influences brain structure and function measured by neuroimaging quantitative traits (QT). Given the high dimensionality of both imaging and genetic data, we propose to study Imaging Genetic Enrichment Analysis (IGEA), a new enrichment analysis paradigm that jointly considers meaningful gene sets (GS) and brain circuits (BC) and examines whether any given GS-BC pair is enriched in a list of gene-QT findings...
March 2017: Brain Informatics
https://www.readbyqxmd.com/read/27720199/connectome-disconnectivity-and-cortical-gene-expression-in-patients-with-schizophrenia
#18
Ingrid A C Romme, Marcel A de Reus, Roel A Ophoff, René S Kahn, Martijn P van den Heuvel
BACKGROUND: Genome-wide association studies have identified several common risk loci for schizophrenia (SCZ). In parallel, neuroimaging studies have shown consistent findings of widespread white matter disconnectivity in patients with SCZ. METHODS: We examined the role of genes in brain connectivity in patients with SCZ by combining transcriptional profiles of 43 SCZ risk genes identified by the recent genome-wide association study of the Schizophrenia Working Group of the Psychiatric Genomics Consortium with data on macroscale connectivity reductions in patients with SCZ...
July 27, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27718423/fine-mapping-the-effects-of-alzheimer-s-disease-risk-loci-on-brain-morphology
#19
Gennady V Roshchupkin, Hieab H Adams, Sven J van der Lee, Meike W Vernooij, Cornelia M van Duijn, Andre G Uitterlinden, Aad van der Lugt, Albert Hofman, Wiro J Niessen, Mohammad A Ikram
The neural substrate of genetic risk variants for Alzheimer's disease (AD) remains unknown. We studied their effect on healthy brain morphology to provide insight into disease etiology in the preclinical phase. We included 4071 nondemented, elderly participants of the population-based Rotterdam Study who underwent brain magnetic resonance imaging and genotyping. We performed voxel-based morphometry (VBM) on all gray-matter voxels for 19 previously identified, common AD risk variants. Whole-brain expression data from the Allen Human Brain Atlas was used to examine spatial overlap between VBM association results and expression of genes in AD risk loci regions...
December 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27354695/abaenrichment-an-r-package-to-test-for-gene-set-expression-enrichment-in-the-adult-and-developing-human-brain
#20
Steffi Grote, Kay Prüfer, Janet Kelso, Michael Dannemann
We present ABAEnrichment, an R package that tests for expression enrichment in specific brain regions at different developmental stages using expression information gathered from multiple regions of the adult and developing human brain, together with ontologically-organized structural information about the brain, both provided by the Allen Brain Atlas. We validate ABAEnrichment by successfully recovering the origin of gene sets identified in specific brain cell-types and developmental stages. AVAILABILITY AND IMPLEMENTATION: ABAEnrichment was implemented as an R package and is available under GPL (>= 2) from the Bioconductor website (http://bioconductor...
June 26, 2016: Bioinformatics
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