scholarly journals Sequence Alterations of Cortical Genes Linked to Individual Connectivity of the Human Brain

2018 ◽  
Vol 29 (9) ◽  
pp. 3828-3835 ◽  
Author(s):  
Qilong Xin ◽  
Laura Ortiz-Terán ◽  
Ibai Diez ◽  
David L Perez ◽  
Julia Ginsburg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Functional Connectivity ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Brain Regions ◽  
Genetic Sequence ◽  
Cortical Areas ◽  
Cortical Regions ◽  
High Degree ◽  
The Brain

Abstract Individual differences in humans are driven by unique brain structural and functional profiles, presumably mediated in part through differential cortical gene expression. However, the relationships between cortical gene expression profiles and individual differences in large-scale neural network organization remain poorly understood. In this study, we aimed to investigate whether the magnitude of sequence alterations in regional cortical genes mapped onto brain areas with high degree of functional connectivity variability across individuals. First, human genetic expression data from the Allen Brain Atlas was used to identify protein-coding genes associated with cortical areas, which delineated the regional genetic signature of specific cortical areas based on sequence alteration profiles. Thereafter, we identified brain regions that manifested high degrees of individual variability by using test-retest functional connectivity magnetic resonance imaging and graph-theory analyses in healthy subjects. We found that rates of genetic sequence alterations shared a distinct spatial topography with cortical regions exhibiting individualized (highly-variable) connectivity profiles. Interestingly, gene expression profiles of brain regions with highly individualized connectivity patterns and elevated number of sequence alterations are devoted to neuropeptide-signaling-pathways and chemical-synaptic-transmission. Our findings support that genetic sequence alterations may underlie important aspects of brain connectome individualities in humans. Significance Statement: The neurobiological underpinnings of our individuality as humans are still an unsolved question. Although the notion that genetic variation drives an individual’s brain organization has been previously postulated, specific links between neural connectivity and gene expression profiles have remained elusive. In this study, we identified the magnitude of population-based sequence alterations in discrete cortical regions and compared them to the brain topological distribution of functional connectivity variability across an independent human sample. We discovered that brain regions with high degree of connectional individuality are defined by increased rates of genetic sequence alterations; these findings specifically implicated genes involved in neuropeptide-signaling pathways and chemical-synaptic transmission. These observations support that genetic sequence alterations may underlie important aspects of the emergence of the brain individuality across humans.

scholarly journals Probabilistic Critical Controllability Analysis of Protein Interaction Networks Integrating Normal Brain Ageing Gene Expression Profiles

2021 ◽  
Vol 22 (18) ◽  
pp. 9891
Author(s):  
Eimi Yamaguchi ◽  
Tatsuya Akutsu ◽  
Jose C. Nacher
Keyword(s):  
Gene Expression ◽  
Biological Networks ◽  
Expression Profiles ◽  
Dominating Set ◽  
Gene Expression Profiles ◽  
Brain Regions ◽  
Normal Brain ◽  
Age Related ◽  
Brain Ageing ◽  
The Brain

Recently, network controllability studies have proposed several frameworks for the control of large complex biological networks using a small number of life molecules. However, age-related changes in the brain have not been investigated from a controllability perspective. In this study, we compiled the gene expression profiles of four normal brain regions from individuals aged 20–99 years and generated dynamic probabilistic protein networks across their lifespan. We developed a new algorithm that efficiently identified critical proteins in probabilistic complex networks, in the context of a minimum dominating set controllability model. The results showed that the identified critical proteins were significantly enriched with well-known ageing genes collected from the GenAge database. In particular, the enrichment observed in replicative and premature senescence biological processes with critical proteins for male samples in the hippocampal region led to the identification of possible new ageing gene candidates.

scholarly journals Distribution of Kakugo Virus and Its Effects on the Gene Expression Profile in the Brain of the Worker Honeybee Apis mellifera L.

2009 ◽  
Vol 83 (22) ◽  
pp. 11560-11568 ◽  
Author(s):  
Tomoko Fujiyuki ◽  
Emiko Matsuzaka ◽  
Takayoshi Nakaoka ◽  
Hideaki Takeuchi ◽  
Akiko Wakamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Leucine Zipper ◽  
Expression Profiles ◽  
Parasitic Wasp ◽  
Gene Expression Profiles ◽  
Hypothetical Protein ◽  
Brain Regions ◽  
Gene Encoding ◽  
Brain Functions ◽  
The Brain

ABSTRACT We previously identified a novel insect picorna-like virus, termed Kakugo virus (KV), obtained from the brains of aggressive honeybee worker bees that had counterattacked giant hornets. Here we examined the tissue distribution of KV and alterations of gene expression profiles in the brains of KV-infected worker bees to analyze possible effects of KV infection on honeybee neural and physiological states. By use of in situ hybridization, KV was broadly detected in the brains of the naturally KV-infected worker bees. When inoculated experimentally into bees, KV was detected in restricted parts of the brain at the early infectious stage and was later detected in various brain regions, including the mushroom bodies, optic lobes, and ocellar nerve. KV was detected not only in the brain but also in the hypopharyngeal glands and fat bodies, indicating systemic KV infection. Next, we compared the gene expression profiles in the brains of KV-inoculated and noninoculated bees. The expression of 11 genes examined was not significantly affected in KV-infected worker bees. cDNA microarray analysis, however, identified a novel gene whose expression was induced in the periphery of the brains of KV-infected bees, which was commonly observed in naturally infected and experimentally inoculated bees. The gene encoded a novel hypothetical protein with a leucine zipper motif. A gene encoding a similar protein was found in the parasitic wasp Nasonia genome but not in other insect genomes. These findings suggest that KV infection may affect brain functions and/or physiological states in honeybees.

scholarly journals Physical positioning markedly enhances brain transduction after intrathecal AAV9 infusion

2018 ◽  
Vol 4 (11) ◽  
pp. eaau9859 ◽  
Author(s):  
Michael J. Castle ◽  
Yuhsiang Cheng ◽  
Aravind Asokan ◽  
Mark H. Tuszynski
Keyword(s):  
Gene Expression ◽  
Gene Delivery ◽  
Neurological Disorders ◽  
Fold Increase ◽  
Brain Regions ◽  
Intrathecal Administration ◽  
Simple Method ◽  
Virus Serotype ◽  
Cortical Regions ◽  
The Brain

Several neurological disorders may benefit from gene therapy. However, even when using the lead vector candidate for intrathecal administration, adeno-associated virus serotype 9 (AAV9), the strength and distribution of gene transfer to the brain are inconsistent. On the basis of preliminary observations that standard intrathecal AAV9 infusions predominantly drive reporter gene expression in brain regions where gravity might cause cerebrospinal fluid to settle, we tested the hypothesis that counteracting vector “settling” through animal positioning would enhance vector delivery to the brain. When rats are either inverted in the Trendelenburg position or continuously rotated after intrathecal AAV9 infusion, we find (i) a significant 15-fold increase in the number of transduced neurons, (ii) a marked increase in gene delivery to cortical regions, and (iii) superior animal-to-animal consistency of gene expression. Entorhinal, prefrontal, frontal, parietal, hippocampal, limbic, and basal forebrain neurons are extensively transduced: 95% of transduced cells are neurons, and greater than 70% are excitatory. These findings provide a novel and simple method for broad gene delivery to the cortex and are of substantial relevance to translational programs for neurological disorders, including Alzheimer’s disease and related dementias, stroke, and traumatic brain injury.

Gene expression profiles in the brain of the neonate mouse perinatally exposed to methylmercury and/or polychlorinated biphenyls

2009 ◽  
Vol 84 (4) ◽  
pp. 271-286 ◽  
Author(s):  
Miyuki Shimada ◽  
Satomi Kameo ◽  
Norio Sugawara ◽  
Kozue Yaginuma-Sakurai ◽  
Naoyuki Kurokawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polychlorinated Biphenyls ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
The Brain

scholarly journals Dynamical consequences of regional heterogeneity in the brain’s transcriptional landscape

2020 ◽  
Author(s):  
Gustavo Deco ◽  
Kevin Aquino ◽  
Aurina Arnatkevičiūtė ◽  
Stuart Oldham ◽  
Kristina Sabaroedin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Brain Regions ◽  
Biophysical Model ◽  
Neuronal Dynamics ◽  
Regional Heterogeneity ◽  
Magnetic Resonance Imaging Mri

AbstractBrain regions vary in their molecular and cellular composition, but how this heterogeneity shapes neuronal dynamics is unclear. Here, we investigate the dynamical consequences of regional heterogeneity using a biophysical model of whole-brain functional magnetic resonance imaging (MRI) dynamics in humans. We show that models in which transcriptional variations in excitatory and inhibitory receptor (E:I) gene expression constrain regional heterogeneity more accurately reproduce the spatiotemporal structure of empirical functional connectivity estimates than do models constrained by global gene expression profiles and MRI-derived estimates of myeloarchitecture. We further show that regional heterogeneity is essential for yielding both ignition-like dynamics, which are thought to support conscious processing, and a wide variance of regional activity timescales, which supports a broad dynamical range. We thus identify a key role for E:I heterogeneity in generating complex neuronal dynamics and demonstrate the viability of using transcriptional data to constrain models of large-scale brain function.

Influenza virus-induced sleep responses in mice with targeted disruptions in neuronal or inducible nitric oxide synthases

2004 ◽  
Vol 97 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Lichao Chen ◽  
Deborah Duricka ◽  
Scott Nelson ◽  
Sanjib Mukherjee ◽  
Stewart G. Bohnet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Eye Movement ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
No Synthase ◽  
Cytokine Gene Expression ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
The Brain

Influenza viral infection induces increases in non-rapid eye movement sleep and decreases in rapid eye movement sleep in normal mice. An array of cytokines is produced during the infection, and some of them, such as IL-1β and TNF-α, are well-defined somnogenic substances. It is suggested that nitric oxide (NO) may mediate the sleep-promoting effects of these cytokines. In this study, we use mice with targeted disruptions of either the neuronal NO synthase (nNOS) or the inducible NO synthase (iNOS) gene, commonly referred to as nNOS or iNOS knockouts (KOs), to investigate sleep changes after influenza viral challenge. We report that the magnitude of viral-induced non-rapid eye movement sleep responses in both nNOS KOs and iNOS KOs was less than that of their respective controls. In addition, the duration of rapid eye movement sleep in nNOS KO mice did not decrease compared with baseline values. All strains of mice had similar viral titers and cytokine gene expression profiles in the lungs. Virus was not isolated from the brains of any strain. However, gene expression in the brain stem differed between nNOS KOs and their controls: mRNA for the interferon-induced gene 2′,5′-oligoadenylate synthase 1a was elevated in nNOS KOs relative to their controls at 15 h, and IL-1β mRNA was elevated in nNOS KOs relative to their controls at 48 h. Our results suggest that NO synthesized by both nNOS and iNOS plays a role in virus-induced sleep changes and that nNOS may modulate cytokine expression in the brain.

scholarly journals Purity and Enrichment of Laser-Microdissected Midbrain Dopamine Neurons

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Amanda L. Brown ◽  
Trevor A. Day ◽  
Christopher V. Dayas ◽  
Doug W. Smith
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Dopamine Neuron ◽  
Dopamine Neurons ◽  
Acid Decarboxylase ◽  
Cell Groups ◽  
Midbrain Dopamine ◽  
High Degree ◽  
Midbrain Dopamine Neurons

The ability to microdissect individual cells from the nervous system has enormous potential, as it can allow for the study of gene expression in phenotypically identified cells. However, if the resultant gene expression profiles are to be accurately ascribed, it is necessary to determine the extent of contamination by nontarget cells in the microdissected sample. Here, we show that midbrain dopamine neurons can be laser-microdissected to a high degree of enrichment and purity. The average enrichment for tyrosine hydroxylase (TH) gene expression in the microdissected sample relative to midbrain sections was approximately 200-fold. For the dopamine transporter (DAT) and the vesicular monoamine transporter type 2 (Vmat2), average enrichments were approximately 100- and 60-fold, respectively. Glutamic acid decarboxylase (Gad65) expression, a marker for GABAergic neurons, was several hundredfold lower than dopamine neuron-specific genes. Glial cell and glutamatergic neuron gene expression were not detected in microdissected samples. Additionally, SN and VTA dopamine neurons had significantly different expression levels of dopamine neuron-specific genes, which likely reflects functional differences between the two cell groups. This study demonstrates that it is possible to laser-microdissect dopamine neurons to a high degree of cell purity. Therefore gene expression profiles can be precisely attributed to the targeted microdissected cells.

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