scholarly journals Schizotypy-related magnetization of cortex in healthy adolescence is co-located with expression of schizophrenia-related genes

2018 ◽  
Author(s):  
Rafael Romero-Garcia ◽  
Jakob Seidlitz ◽  
Kirstie J Whitaker ◽  
Sarah E Morgan ◽  
Peter Fonagy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Magnetization Transfer ◽  
Gene Expression Pattern ◽  
Structural Mri ◽  
Brain Regions ◽  
Posterior Cingulate Cortex ◽  
Genomic Variation ◽  
Adult Brain ◽  
Brain Gene Expression ◽  
Histological Data

AbstractBackgroundGenetic risk is thought to drive clinical variation on a spectrum of schizophrenia-like traits but the underlying changes in brain structure that mechanistically link genomic variation to schizotypal experience and behaviour are unclear.MethodsWe assessed schizotypy using a self-reported questionnaire, and measured magnetization transfer (MT), as a putative micro-structural MRI marker of intra-cortical myelination, in 68 brain regions, in 248 healthy young people (aged 14-25 years). We used normative adult brain gene expression data, and partial least squares (PLS) analysis, to find the weighted gene expression pattern that was most co-located with the cortical map of schizotypy-related magnetization (SRM).ResultsMagnetization was significantly correlated with schizotypy in bilateral posterior cingulate cortex and precuneus (and for disorganized schizotypy also in medial prefrontal cortex; all FDR-corrected P < 0.05), which are regions of the default mode network specialized for social and memory functions. The genes most positively weighted on the whole genome expression map co-located with SRM were enriched for genes that were significantly down-regulated in two prior case-control histological studies of brain gene expression in schizophrenia. Conversely, the most negatively weighted genes were enriched for genes that were transcriptionally up-regulated in schizophrenia. Positively weighted (down-regulated) genes were enriched for neuronal, specifically inter-neuronal, affiliations and coded a network of proteins comprising a few highly interactive “hubs” such as parvalbumin and calmodulin.ConclusionsMicrostructural MRI maps of intracortical magnetization can be linked to both the behavioural traits of schizotypy and to prior histological data on dysregulated gene expression in schizophrenia.

scholarly journals Quantitative RT-PCR analyses of five evolutionary conserved genes in Alligator brains during development

2011 ◽  
Vol 2 (4) ◽  
Author(s):  
Sarah Wilson ◽  
Tianli Zhu ◽  
Rajesh Khanna ◽  
Michael Pritz
Keyword(s):  
Gene Expression ◽  
Brain Area ◽  
Brain Regions ◽  
Adult Brain ◽  
Time Interval ◽  
Conserved Genes ◽  
Mrna Gene ◽  
Alligator Mississipiensis ◽  
Mrna Gene Expression ◽  
Present Gene

AbstractGene expression was investigated in the major brain subdivisions (telencephalon, diencephalon, midbrain and hindbrain) in a representative reptile, Alligator mississipiensis, during the later stages of embryonic development. The following genes were examined: voltage-gated sodium channel isoforms: NaV1.1 and NaV1.2; synaptic vesicle 2a (SV2a); synaptophysin; and calbindin 2. With the exception of synaptophysin, which was only expressed in the telencephalon, all genes were expressed in all brain regions sampled at the time periods examined. For NaV1.1, gene expression varied according to brain area sampled. When compared with NaV1.1, the pattern of NaV1.2 gene expression differed appreciably. The gene expression of SV2a was the most robust of any of the genes examined. Of the other genes examined, although differences were noted, no statistically significant changes were found either between brain part or time interval. Although limited, the present analysis is the first quantitative mRNA gene expression study in any reptile during development. Together with future experiments of a similar nature, the present gene expression results should determine which genes are expressed in major brain areas at which times during development in Alligator. When compared with other amniotes, these results will prove useful for determining how gene expression during development influences adult brain structure.

scholarly journals Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142630 ◽  
Author(s):  
Monika Burns ◽  
Sureshkumar Muthupalani ◽  
Zhongming Ge ◽  
Timothy C. Wang ◽  
Vasudevan Bakthavatchalu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Helicobacter Pylori ◽  
Serum Iron ◽  
Adult Brain ◽  
Helicobacter Pylori Infection ◽  
Iron Storage ◽  
Brain Gene Expression

scholarly journals Brain Gene Expression Pattern of Subjects with Completed Suicide and Comorbid Substance Use Disorder

2018 ◽  
Vol 5 (1) ◽  
pp. 60-73 ◽  
Author(s):  
Brenda Cabrera ◽  
Nancy Monroy-Jaramillo ◽  
Gabriel Rodrigo Fries ◽  
Roberto Cuauhtemoc Mendoza-Morales ◽  
Fernando García-Dolores ◽  
...  
Keyword(s):  
Gene Expression ◽  
Substance Use ◽  
Expression Pattern ◽  
Substance Use Disorder ◽  
Gene Expression Pattern ◽  
Brain Gene Expression ◽  
Completed Suicide

scholarly journals Cortical diurnal rhythms remain intact with microglial depletion

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Rocio A. Barahona ◽  
Samuel Morabito ◽  
Vivek Swarup ◽  
Kim N. Green
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Brain Regions ◽  
Adult Brain ◽  
Diurnal Rhythms ◽  
Dark Phase ◽  
Perineuronal Nets ◽  
Diurnal Changes ◽  
Cycling Gene ◽  
Diurnal Regulation

AbstractMicroglia are subject to change in tandem with the endogenously generated biological oscillations known as our circadian rhythm. Studies have shown microglia harbor an intrinsic molecular clock which regulates diurnal changes in morphology and influences inflammatory responses. In the adult brain, microglia play an important role in the regulation of condensed extracellular matrix structures called perineuronal nets (PNNs), and it has been suggested that PNNs are also regulated in a circadian and diurnal manner. We sought to determine whether microglia mediate the diurnal regulation of PNNs via CSF1R inhibitor dependent microglial depletion in C57BL/6J mice, and how the absence of microglia might affect cortical diurnal gene expression rhythms. While we observe diurnal differences in microglial morphology, where microglia are most ramified at the onset of the dark phase, we do not find diurnal differences in PNN intensity. However, PNN intensity increases across many brain regions in the absence of microglia, supporting a role for microglia in the regulation of PNNs. Here, we also show that cortical diurnal gene expression rhythms are intact, with no cycling gene changes without microglia. These findings demonstrate a role for microglia in the maintenance of PNNs, but not in the maintenance of diurnal rhythms.

scholarly journals Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Diego Marques-Coelho ◽  
◽  
Lukas da Cruz Carvalho Iohan ◽  
Ana Raquel Melo de Farias ◽  
Amandine Flaig ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Expression ◽  
Cell Types ◽  
Brain Regions ◽  
Adult Brain ◽  
Gene Transcript ◽  
Comprehensive Overview ◽  
Gene Expression Alterations

AbstractAlzheimer’s disease (AD) is the leading cause of dementia in aging individuals. Yet, the pathophysiological processes involved in AD onset and progression are still poorly understood. Among numerous strategies, a comprehensive overview of gene expression alterations in the diseased brain could contribute for a better understanding of the AD pathology. In this work, we probed the differential expression of genes in different brain regions of healthy and AD adult subjects using data from three large transcriptomic studies: Mayo Clinic, Mount Sinai Brain Bank (MSBB), and ROSMAP. Using a combination of differential expression of gene and isoform switch analyses, we provide a detailed landscape of gene expression alterations in the temporal and frontal lobes, harboring brain areas affected at early and late stages of the AD pathology, respectively. Next, we took advantage of an indirect approach to assign the complex gene expression changes revealed in bulk RNAseq to individual cell types/subtypes of the adult brain. This strategy allowed us to identify previously overlooked gene expression changes in the brain of AD patients. Among these alterations, we show isoform switches in the AD causal gene amyloid-beta precursor protein (APP) and the risk gene bridging integrator 1 (BIN1), which could have important functional consequences in neuronal cells. Altogether, our work proposes a novel integrative strategy to analyze RNAseq data in AD and other neurodegenerative diseases based on both gene/transcript expression and regional/cell-type specificities.

scholarly journals Isolation disrupts social interactions and destabilizes brain development in bumblebees

2021 ◽  
Author(s):  
Z Yan Wang ◽  
Grace C. McKenzie-Smith ◽  
Weijie Liu ◽  
Hyo Jin Cho ◽  
Talmo D Pereira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Development ◽  
Social Interactions ◽  
Social Isolation ◽  
Small Groups ◽  
Early Life ◽  
Brain Regions ◽  
Brain Gene Expression ◽  
Rearing Condition ◽  
The Impact

Social isolation, particularly in early life, leads to deleterious physiological and behavioral outcomes. Few studies, if any, have been able to capture the behavioral and neurogenomic consequences of early life social isolation together in a single social animal system. Here, we leverage new high-throughput tools to comprehensively investigate the impact of isolation in the bumblebee (Bombus impatiens) from behavioral, molecular, and neuroanatomical perspectives. We reared newly emerged bumblebees either in complete isolation, small groups, or in their natal colony, and then analyzed their behaviors while alone or paired with another bee. We find that when alone, individuals of each rearing condition show distinct behavioral signatures. When paired with a conspecific, bees reared in small groups or in the natal colony express similar behavioral profiles. Isolated bees, however, showed increased social interactions. To identify the neurobiological correlates of these differences, we quantified brain gene expression and measured the volumes of key brain regions for a subset of individuals from each rearing condition. Overall, we find that isolation increases social interactions and disrupts gene expression and brain development. Limited social experience in small groups is sufficient to preserve typical patterns of brain development and social behavior.

scholarly journals Sex-biased gene expression in rhesus macaque and human brains

2020 ◽  
Author(s):  
Alex R. DeCasien ◽  
Chet C. Sherwood ◽  
James P. Higham
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Sexual Selection ◽  
Cognitive Abilities ◽  
Rhesus Macaques ◽  
Purifying Selection ◽  
Brain Regions ◽  
Sexually Dimorphic ◽  
Brain Gene Expression ◽  
Human Brains

AbstractSexually dimorphic traits (i.e. phenotypic differences between males and females) are largely produced by sex-biased gene expression (i.e. differential expression of genes present in both sexes). These expression differences may be the result of sexual selection, although other factors (e.g., relaxed purifying selection, pleiotropy, dosage compensation) also contribute. Given that humans and other primates exhibit sex differences in cognition and neuroanatomy, this implicates sex differences in brain gene expression. Here, we compare sex-biased gene expression in humans and rhesus macaques across 16 brain regions using published RNA-Seq datasets. Our results demonstrate that most sex-biased genes are differentially expressed between species, and that overlap across species is limited. Human brains are relatively more sexually dimorphic and exhibit more male-than female-biased genes. Across species, gene expression is biased in opposite directions in some regions and in the same direction in others, suggesting that the latter may be more relevant in nonhuman primate models of neurological disorders. Finally, the brains of both species exhibit positive correlations between sex effects across regions, higher tissue specificity among sex-biased genes, enrichment of extracellular matrix among male-biased genes, and regulation of sex-biased genes by sex hormones. Taken together, our results demonstrate some conserved mechanisms underlying sex-biased brain gene expression, while also suggesting that increased neurodevelopmental plasticity and/or strong sexual selection on cognitive abilities may have played a role in shaping sex-biased brain gene expression in the human lineage.

scholarly journals Molecular Atlas of the Adult Mouse Brain

2019 ◽  
Author(s):  
Cantin Ortiz ◽  
Jose Fernandez Navarro ◽  
Aleksandra Jurek ◽  
Antje Märtin ◽  
Joakim Lundeberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Spatial Organization ◽  
Adult Mouse ◽  
Brain Regions ◽  
Adult Brain ◽  
Adult Mouse Brain ◽  
Whole Brain ◽  
Systematic Classification ◽  
Molecular Code

AbstractBrain maps are essential for integrating information and interpreting the structure-function relationship of circuits and behavior. We aimed to generate a systematic classification of the adult mouse brain organization based on unbiased extraction of spatially-defining features. Applying whole-brain spatial transcriptomics, we captured the gene expression signatures to define the spatial organization of molecularly discrete subregions. We found that the molecular code contained sufficiently detailed information to directly deduce the complex spatial organization of the brain. This unsupervised molecular classification revealed new area- and layer-specific subregions, for example in isocortex and hippocampus, and a new division of striatum. The whole-brain molecular atlas further supports the identification of the spatial origin of single neurons using their gene expression profile, and forms the foundation to define a minimal gene set - a brain palette – that is sufficient to spatially annotate the adult brain. In summary, we have established a new molecular atlas to formally define the identity of brain regions, and a molecular code for mapping and targeting of discrete neuroanatomical domains.

scholarly journals Differential transcript usage unravels gene expression alterations in Alzheimer’s disease human brains

2020 ◽  
Author(s):  
Diego Marques-Coelho ◽  
Lukas Iohan da Cruz Carvalho ◽  
Ana Raquel Melo de Farias ◽  
Jean-Charles Lambert ◽  
Marcos Romualdo Costa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Expression ◽  
Brain Regions ◽  
Adult Brain ◽  
Gene Transcript ◽  
Cell Type ◽  
Comprehensive Overview ◽  
Gene Expression Alterations

AbstractAlzheimer’s disease (AD) is the leading cause of dementia in aging individuals. However pathophysiological processes involved in the brain are still poorly understood. Among numerous strategies, a comprehensive overview of gene expression alterations in the diseased brain has been proposed to help for a better understanding of the disease processes. In this work, we probed the differential expression of genes in different brain regions of healthy and AD adult subjects using data from three large studies: MAYO Clinic; Mount Sinai Brain Bank (MSBB) and ROSMAP. Using a combination of differential expression of gene (DEG) and isoform switch analyses we provide a detailed landscape of gene expression alterations in the temporal and frontal lobes, harboring brain areas affected at early and late stages of the AD pathology, respectively. Next, we took advantage of an indirect approach to assign the complex gene expression changes revealed in bulk RNAseq to individual cell types of the adult brain. This strategy allowed us to identify cell type/subtype specific isoform switches in AD brains previously overlooked. This was the case, for example, for the AD causal gene APP and the risk gene BIN1, which presented isoform switches with potential functional consequences in neuronal cells. Altogether, our work proposes a novel integrative strategy to analyze RNAseq data in AD based on both gene/transcript expression and regional/cell-type specificities.

scholarly journals Where Environment Meets Cognition: A Focus on Two Developmental Intellectual Disability Disorders

2016 ◽  
Vol 2016 ◽  
pp. 1-20 ◽  
Author(s):  
I. De Toma ◽  
L. Manubens Gil ◽  
S. Ossowski ◽  
M. Dierssen
Keyword(s):  
Gene Expression ◽  
Intellectual Disability ◽  
Fragile X ◽  
Chromatin Accessibility ◽  
Adult Brain ◽  
Epigenetic Alterations ◽  
Brain Gene Expression ◽  
Epigenetic Machinery ◽  
Context Specific ◽  
Global And Local

One of the most challenging questions in neuroscience is to dissect how learning and memory, the foundational pillars of cognition, are grounded in stable, yet plastic, gene expression states. All known epigenetic mechanisms such as DNA methylation and hydroxymethylation, histone modifications, chromatin remodelling, and noncoding RNAs regulate brain gene expression, both during neurodevelopment and in the adult brain in processes related to cognition. On the other hand, alterations in the various components of the epigenetic machinery have been linked to well-known causes of intellectual disability disorders (IDDs). Two examples are Down Syndrome (DS) and Fragile X Syndrome (FXS), where global and local epigenetic alterations lead to impairments in synaptic plasticity, memory, and learning. Since epigenetic modifications are reversible, it is theoretically possible to use epigenetic drugs as cognitive enhancers for the treatment of IDDs. Epigenetic treatments act in a context specific manner, targeting different regions based on cell and state specific chromatin accessibility, facilitating the establishment of the lost balance. Here, we discuss epigenetic studies of IDDs, focusing on DS and FXS, and the use of epidrugs in combinatorial therapies for IDDs.

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