Early specification and autonomous development of cortical fields in the mouse hippocampus

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 4959-4970 ◽  
Author(s):  
S. Tole ◽  
C. Christian ◽  
E.A. Grove
Keyword(s):  
Gene Expression ◽  
Slice Culture ◽  
Field Development ◽  
Cortical Areas ◽  
Hippocampal Field ◽  
Mouse Hippocampus ◽  
Hippocampal Development ◽  
Autonomous Development ◽  
The Brain ◽  
Development Proceeds

Studies of the specification of distinct areas in the developing cerebral cortex have until now focused mainly on neocortex. We demonstrate that the hippocampus, an archicortical structure, offers an elegant, alternative system in which to explore cortical area specification. Individual hippocampal areas, called CA fields, display striking molecular differences in maturity. We use these distinct patterns of gene expression as markers of CA field identity, and show that the two major hippocampal fields, CA1 and CA3, are specified early in hippocampal development, during the period of neurogenesis. Two field-specific markers display consistent patterns of expression from the embryo to the adult. Presumptive CA1 and CA3 fields (Pca1, Pca3) can therefore be identified between embryonic days 14.5 and 15.5 in the mouse, a week before the fields are morphologically distinct. No other individual cortical areas have been detected by gene expression as early in development. Indeed, other features that distinguish between the CA fields appear after birth, indicating that mature CA field identity is acquired over at least 3 weeks. To determine if Pca1 and Pca3 are already specified to acquire mature CA field identities, the embryonic fields were isolated from further potential specification cues by maintaining them in slice culture. CA field development proceeds in slices of the entire embryonic hippocampus. More strikingly, slices restricted to Pca1 or Pca3 alone also develop appropriate mature features of CA1 or CA3. Pca1 and Pca3 are therefore able to develop complex characteristics of mature CA field identity autonomously, that is, without contact or innervation from other fields or other parts of the brain. Because Pca1 and Pca3 can be identified before major afferents grow into the hippocampus, innervation may also be unnecessary for the initial division of the hippocampus into separate fields. Providing a clue to the source of the true specifying signals, the earliest field markers appear first at the poles of the hippocampus, then progress inwards. General hippocampal development does not follow this pronounced pattern. We suggest that the sources of signals that specify hippocampal field identity lie close to the hippocampal poles, and that the signals operate first on cells at the poles, then move inwards.

scholarly journals The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Shoug M. Alashmali ◽  
Lin Lin ◽  
Marc-Olivier Trépanier ◽  
Giulia Cisbani ◽  
Richard P. Bazinet
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Diet Group ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Left Lateral Ventricle ◽  
Gene Response ◽  
Mouse Hippocampus ◽  
Total Fatty Acids ◽  
The Brain

Abstract Background Neuroinflammation is thought to contribute to psychiatric and neurological disorders such as major depression and Alzheimer’s disease (AD). N-6 polyunsaturated fatty acids (PUFA) and molecules derived from them, including linoleic acid- and arachidonic acid-derived lipid mediators, are known to have pro-inflammatory properties in the periphery; however, this has yet to be tested in the brain. Lowering the consumption of n-6 PUFA is associated with a decreased risk of depression and AD in human observational studies. The purpose of this study was to investigate the inflammation-modulating effects of lowering dietary n-6 PUFA in the mouse hippocampus. Methods C57BL/6 male mice were fed either an n-6 PUFA deprived (2% of total fatty acids) or an n-6 PUFA adequate (23% of total fatty acids) diet from weaning to 12 weeks of age. Animals then underwent intracerebroventricular surgery, in which lipopolysaccharide (LPS) was injected into the left lateral ventricle of the brain. Hippocampi were collected at baseline and following LPS administration (1, 3, 7, and 14 days). A microarray (n = 3 per group) was used to identify candidate genes and results were validated by real-time PCR in a separate cohort of animals (n = 5–8 per group). Results Mice administered with LPS had significantly increased Gene Ontology categories associated with inflammation and immune responses. These effects were independent of changes in gene expression in any diet group. Results were validated for the effect of LPS treatment on astrocyte, cytokine, and chemokine markers, as well as some results of the diets on Ifrd2 and Mfsd2a expression. Conclusions LPS administration increases pro-inflammatory and lipid-metabolizing gene expression in the mouse hippocampus. An n-6 PUFA deprived diet modulated inflammatory gene expression by both increasing and decreasing inflammatory gene expression, without impairing the resolution of neuroinflammation following LPS administration.

scholarly journals Age-related changes of gene expression in the neocortex: Preliminary data on RNA-Seq of the transcriptome in three functionally distinct cortical areas

2012 ◽  
Vol 24 (4) ◽  
pp. 1427-1442 ◽  
Author(s):  
Oksana Yu. Naumova ◽  
Dean Palejev ◽  
Natalia V. Vlasova ◽  
Maria Lee ◽  
Sergei Yu. Rychkov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Rna Seq ◽  
Signaling Systems ◽  
Cortical Areas ◽  
Age Related ◽  
Transcriptional Changes ◽  
Atypical Development ◽  
The Brain ◽  
Age Related Changes

AbstractThe study of gene expression (i.e., the study of the transcriptome) in different cells and tissues allows us to understand the molecular mechanisms of their differentiation, development and functioning. In this article, we describe some studies of gene-expression profiling for the purposes of understanding developmental (age-related) changes in the brain using different technologies (e.g., DNA-Microarray) and the new and increasingly popular RNA-Seq. We focus on advancements in studies of gene expression in the human brain, which have provided data on the structure and age-related variability of the transcriptome in the brain. We present data on RNA-Seq of the transcriptome in three distinct areas of the neocortex from different ages: mature and elderly individuals. We report that most age-related transcriptional changes affect cellular signaling systems, and, as a result, the transmission of nerve impulses. In general, the results demonstrate the high potential of RNA-Seq for the study of distinctive features of gene expression among cortical areas and the changes in expression through normal and atypical development of the central nervous system.

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.

1805-P: Insulin Regulates a Broad Network of Gene Expression in the Brain to Regulated Brain Metabolism and Neurotransmission

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1805-P
Author(s):  
WEIKANG CAI ◽  
THIAGO M. BATISTA ◽  
RUBEN GARCIA MARTIN ◽  
ALFRED RAMIREZ ◽  
MASAHIRO KONISHI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Metabolism ◽  
The Brain

scholarly journals Alternative splicing during mammalian organ development

2021 ◽  
Author(s):  
Pavel V. Mazin ◽  
Philipp Khaitovich ◽  
Margarida Cardoso-Moreira ◽  
Henrik Kaessmann
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Regulatory Networks ◽  
Organ Development ◽  
Functional Diversification ◽  
Mammalian Genomes ◽  
Species Comparisons ◽  
Time Specific ◽  
The Brain ◽  
Gene Expression Levels

AbstractAlternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.

scholarly journals LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models

2021 ◽  
Vol 7 (11) ◽  
pp. eaba1187
Author(s):  
Rina Baba ◽  
Satoru Matsuda ◽  
Yuuichi Arakawa ◽  
Ryuji Yamada ◽  
Noriko Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Specific Inhibitor ◽  
Autism Spectrum ◽  
Poly I:C ◽  
Control Of Gene Expression ◽  
Epigenetic Machinery ◽  
The Brain

Persistent epigenetic dysregulation may underlie the pathophysiology of neurodevelopmental disorders, such as autism spectrum disorder (ASD). Here, we show that the inhibition of lysine-specific demethylase 1 (LSD1) enzyme activity normalizes aberrant epigenetic control of gene expression in neurodevelopmental disorders. Maternal exposure to valproate or poly I:C caused sustained dysregulation of gene expression in the brain and ASD-like social and cognitive deficits after birth in rodents. Unexpectedly, a specific inhibitor of LSD1 enzyme activity, 5-((1R,2R)-2-((cyclopropylmethyl)amino)cyclopropyl)-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide hydrochloride (TAK-418), almost completely normalized the dysregulated gene expression in the brain and ameliorated some ASD-like behaviors in these models. The genes modulated by TAK-418 were almost completely different across the models and their ages. These results suggest that LSD1 enzyme activity may stabilize the aberrant epigenetic machinery in neurodevelopmental disorders, and the inhibition of LSD1 enzyme activity may be the master key to recover gene expression homeostasis. TAK-418 may benefit patients with neurodevelopmental disorders.

scholarly journals A gene expression atlas for different kinds of stress in the mouse brain

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Tiziano Flati ◽  
Silvia Gioiosa ◽  
Giovanni Chillemi ◽  
Andrea Mele ◽  
Alberto Oliverio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Coping With Stress ◽  
Gene Expression Atlas ◽  
Sequence Read Archive ◽  
Brain Transcriptome ◽  
Expression Atlas ◽  
Differential Gene ◽  
Stress Related Genes ◽  
Public Repositories ◽  
The Brain

AbstractStressful experiences are part of everyday life and animals have evolved physiological and behavioral responses aimed at coping with stress and maintaining homeostasis. However, repeated or intense stress can induce maladaptive reactions leading to behavioral disorders. Adaptations in the brain, mediated by changes in gene expression, have a crucial role in the stress response. Recent years have seen a tremendous increase in studies on the transcriptional effects of stress. The input raw data are freely available from public repositories and represent a wealth of information for further global and integrative retrospective analyses. We downloaded from the Sequence Read Archive 751 samples (SRA-experiments), from 18 independent BioProjects studying the effects of different stressors on the brain transcriptome in mice. We performed a massive bioinformatics re-analysis applying a single, standardized pipeline for computing differential gene expression. This data mining allowed the identification of novel candidate stress-related genes and specific signatures associated with different stress conditions. The large amount of computational results produced was systematized in the interactive “Stress Mice Portal”.

scholarly journals The brain transcriptome of the wolf spider, Schizocosa ocreata

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Daniel Stribling ◽  
Peter L. Chang ◽  
Justin E. Dalton ◽  
Christopher A. Conow ◽  
Malcolm Rosenthal ◽  
...  
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Model Organisms ◽  
De Novo Transcriptome Assembly ◽  
De Novo Transcriptome ◽  
Wolf Spiders ◽  
Schizocosa Ocreata ◽  
Genomic Studies ◽  
The Brain

Abstract Objectives Arachnids have fascinating and unique biology, particularly for questions on sex differences and behavior, creating the potential for development of powerful emerging models in this group. Recent advances in genomic techniques have paved the way for a significant increase in the breadth of genomic studies in non-model organisms. One growing area of research is comparative transcriptomics. When phylogenetic relationships to model organisms are known, comparative genomic studies provide context for analysis of homologous genes and pathways. The goal of this study was to lay the groundwork for comparative transcriptomics of sex differences in the brain of wolf spiders, a non-model organism of the pyhlum Euarthropoda, by generating transcriptomes and analyzing gene expression. Data description To examine sex-differential gene expression, short read transcript sequencing and de novo transcriptome assembly were performed. Messenger RNA was isolated from brain tissue of male and female subadult and mature wolf spiders (Schizocosa ocreata). The raw data consist of sequences for the two different life stages in each sex. Computational analyses on these data include de novo transcriptome assembly and differential expression analyses. Sample-specific and combined transcriptomes, gene annotations, and differential expression results are described in this data note and are available from publicly-available databases.

scholarly journals Bile Acids in Dementia: Brain Amyloid, White Matter Lesions, and Atrophy

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 767-768
Author(s):  
Vijay Varma ◽  
Youjin Wang ◽  
Yang An ◽  
Sudhir Varma ◽  
Murat Bilgel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bile Acids ◽  
White Matter Lesions ◽  
Pharmacological Modulation ◽  
Dementia Risk ◽  
The Brain ◽  
Step Study ◽  
Brain Amyloid Deposition ◽  
Gene Expression Levels

Abstract While Alzheimer’s disease (AD) and vascular dementia (VaD) may be accelerated by hypercholesterolemia, the mechanisms underlying this association is unclear. Using a novel, 3-step study design we examined the role of cholesterol catabolism in dementia by testing whether 1) the synthesis of the primary cholesterol breakdown products (bile acids (BA)) were associated with neuroimaging markers of dementia; 2) pharmacological modulation of BAs alters dementia risk; and 3) brain BA concentrations and gene expression were associated with AD. We found that higher serum concentrations of BAs are associated with lower brain amyloid deposition, slower WML accumulation, and slower brain atrophy in males. Opposite effects were observed in females. Modulation of BA levels alters risk of incident VaD in males. Altered brain BA signaling at the metabolite and gene expression levels occurs in AD. Dysregulation of peripheral cholesterol catabolism and BA synthesis may impact dementia pathogenesis through signaling pathways in the brain.

scholarly journals Interaction of clozapine with metformin in a schizophrenia rat model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
G. Horvath ◽  
G. Kis ◽  
G. Kekesi ◽  
A. Büki ◽  
L. G. Adlan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cognitive Function ◽  
Negative Symptoms ◽  
Antipsychotic Drugs ◽  
D1 Receptor ◽  
Antidiabetic Drug ◽  
Beneficial Effects ◽  
Adjuvant Therapies ◽  
Behavioral Parameters ◽  
The Brain

AbstractThe low efficacy of antipsychotic drugs (e.g., clozapine) for negative symptoms and cognitive impairment has led to the introduction of adjuvant therapies. Because previous data suggest the procognitive potential of the antidiabetic drug metformin, this study aimed to assess the effects of chronic clozapine and metformin oral administration (alone and in combination) on locomotor and exploratory activities and cognitive function in a reward-based test in control and a schizophrenia-like animal model (Wisket rats). As impaired dopamine D1 receptor (D1R) function might play a role in the cognitive dysfunctions observed in patients with schizophrenia, the second goal of this study was to determine the brain-region-specific D1R-mediated signaling, ligand binding, and mRNA expression. None of the treatments affected the behavior of the control animals significantly; however, the combination treatment enhanced D1R binding and activation in the cerebral cortex. The Wisket rats exhibited impaired motivation, attention, and cognitive function, as well as a lower level of cortical D1R binding, signaling, and gene expression. Clozapine caused further deterioration of the behavioral parameters, without a significant effect on the D1R system. Metformin blunted the clozapine-induced impairments, and, similarly to that observed in the control animals, increased the functional activity of D1R. This study highlights the beneficial effects of metformin (at the behavioral and cellular levels) in blunting clozapine-induced adverse effects.

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