scholarly journals Dynamic Changes of Brain Cilia Transcriptomes across the Human Lifespan

2021 ◽  
Vol 22 (19) ◽  
pp. 10387
Author(s):  
Siwei Chen ◽  
Wedad Alhassen ◽  
Roudabeh Vakil Monfared ◽  
Benjamin Vachirakorntong ◽  
Surya M. Nauli ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Expression Patterns ◽  
Brain Regions ◽  
Adult Brain ◽  
Brain Functions ◽  
Human Lifespan ◽  
Age Related ◽  
Age Dependent ◽  
Almost All ◽  
Functional Components

Almost all brain cells contain primary cilia, antennae-like microtubule sensory organelles, on their surface, which play critical roles in brain functions. During neurodevelopmental stages, cilia are essential for brain formation and maturation. In the adult brain, cilia play vital roles as signaling hubs that receive and transduce various signals and regulate cell-to-cell communications. These distinct roles suggest that cilia functions, and probably structures, change throughout the human lifespan. To further understand the age-dependent changes in cilia roles, we identified and analyzed age-dependent patterns of expression of cilia’s structural and functional components across the human lifespan. We acquired cilia transcriptomic data for 16 brain regions from the BrainSpan Atlas and analyzed the age-dependent expression patterns using a linear regression model by calculating the regression coefficient. We found that 67% of cilia transcripts were differentially expressed genes with age (DEGAs) in at least one brain region. The age-dependent expression was region-specific, with the highest and lowest numbers of DEGAs expressed in the ventrolateral prefrontal cortex and hippocampus, respectively. The majority of cilia DEGAs displayed upregulation with age in most of the brain regions. The transcripts encoding cilia basal body components formed the majority of cilia DEGAs, and adjacent cerebral cortices exhibited large overlapping pairs of cilia DEGAs. Most remarkably, specific α/β-tubulin subunits (TUBA1A, TUBB2A, and TUBB2B) and SNAP-25 exhibited the highest rates of downregulation and upregulation, respectively, across age in almost all brain regions. α/β-tubulins and SNAP-25 expressions are known to be dysregulated in age-related neurodevelopmental and neurodegenerative disorders. Our results support a role for the high dynamics of cilia structural and functional components across the lifespan in the normal physiology of brain circuits. Furthermore, they suggest a crucial role for cilia signaling in the pathophysiological mechanisms of age-related psychiatric/neurological disorders.

scholarly journals Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain

2015 ◽  
Vol 112 (22) ◽  
pp. 6855-6862 ◽  
Author(s):  
Loyal A. Goff ◽  
Abigail F. Groff ◽  
Martin Sauvageau ◽  
Zachary Trayes-Gibson ◽  
Diana B. Sanchez-Gomez ◽  
...  
Keyword(s):  
Neural Development ◽  
Expression Patterns ◽  
Noncoding Rnas ◽  
Brain Regions ◽  
Long Noncoding Rnas ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Endogenous Expression ◽  
Spatiotemporal Expression

Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. However, the in vivo expression dynamics and molecular pathways regulated by these loci are not well understood. Here, we leveraged a cohort of 13 lncRNA-null mutant mouse models to investigate the spatiotemporal expression of lncRNAs in the developing and adult brain and the transcriptome alterations resulting from the loss of these lncRNA loci. We show that several lncRNAs are differentially expressed both in time and space, with some presenting highly restricted expression in only selected brain regions. We further demonstrate altered regulation of genes for a large variety of cellular pathways and processes upon deletion of the lncRNA loci. Finally, we found that 4 of the 13 lncRNAs significantly affect the expression of several neighboring protein-coding genes in a cis-like manner. By providing insight into the endogenous expression patterns and the transcriptional perturbations caused by deletion of the lncRNA locus in the developing and postnatal mammalian brain, these data provide a resource to facilitate future examination of the specific functional relevance of these genes in neural development, brain function, and disease.

scholarly journals The Participation of Hormones in the Processes of Cognitive and Socio-Emotional Aging

2020 ◽  
Vol 6 (8) ◽  
pp. 97-129
Author(s):  
S. Bulgakova ◽  
N. Romanchuk
Keyword(s):  
Sex Hormones ◽  
Neural Plasticity ◽  
Emotion Dysregulation ◽  
Emotional Functioning ◽  
Progesterone Receptors ◽  
Endocrine System ◽  
Neurite Growth ◽  
Brain Regions ◽  
Adult Brain ◽  
Brain Functions

Aging is associated with generally accepted changes in brain functions, including cognitive ones. In addition, age makes its own adjustments to the work of the endocrine system. In turn, a change in the hormonal background during the aging process imprints the work of brain cells, cognitive functions, and socio-emotional functioning. Investigated, the relationship between sex hormones, cortisol, oxytocin and cognitive and socio-emotional functioning. Sex hormones are involved in neurite growth, synaptogenesis, dendritic branching, myelination, and other important mechanisms of neural plasticity. Physiological and pathological conceptualized theories suggest how sex hormones potentially cause neuroplasticity changes through four neurochemical neurotransmitter systems: serotonin, dopamine, GABA and glutamate. Many brain regions express high density estrogen and progesterone receptors such as the amygdala, hypothalamus, and hippocampus. The hippocampus is of particular importance in the context of mediating structural plasticity in the adult brain, differences in behavior, neurochemical patterns and structure of the hippocampus with a changing hormonal environment have been investigated. There is a significant association between emotion dysregulation and symptoms of depression, anxiety, eating pathology, and substance abuse. Higher levels of emotion regulation are associated with a high level of social competence.

A Qualitative Analysis Based on Relative Expression Orderings Identifies Transcriptional Subgroups for Alzheimer’s Disease

2020 ◽  
Vol 16 (13) ◽  
pp. 1175-1182 ◽  
Author(s):  
Guini Hong ◽  
Pengming Zeng ◽  
Na Li ◽  
Hao Cai ◽  
You Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Region ◽  
Expression Patterns ◽  
Brain Regions ◽  
Gene Expression Patterns ◽  
Relative Expression ◽  
Age Related ◽  
Relative Expression Orderings

Background: Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease. However, few studies have investigated the heterogeneous gene expression patterns in AD. Objective and Methods: We examined the gene expression patterns in four brain regions of AD based on the within-sample relative expression orderings (REOs). Gene pairs with significantly reversed REOs in AD samples compared to non-AD controls were identified for each brain region using Fisher’s exact test, and filtered according to their transcriptional differences between AD samples. Subgroups of AD were classified by cluster analysis. Results: REO-based gene expression profiling analyses revealed that transcriptional differences, as well as distinct disease subsets, existed within AD patients. For each brain region, two main subgroups were classified: one subgroup reported differentially expressed genes overlapped with the age-related genes, and the other might relate to neuroinflammation. Conclusion: AD transcriptional subgroups might help understand the underlying pathogenesis of AD, and lend support to a personalized approach to AD management.

scholarly journals Postnatal Guinea Pig Brain Development, as Revealed by Magnetic Resonance and Diffusion Kurtosis Imaging

2020 ◽  
Vol 10 (6) ◽  
pp. 365
Author(s):  
Roger J. Mullins ◽  
Su Xu ◽  
Jiachen Zhuo ◽  
Steve Roys ◽  
Edna F.R. Pereira ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Brain Regions ◽  
Whole Brain ◽  
Pig Brain ◽  
Age Related ◽  
Age Dependent ◽  
Diffusion Kurtosis ◽  
Guinea Pig Brain

This study used in vivo magnetic resonance imaging (MRI) to identify age dependent brain structural characteristics in Dunkin Hartley guinea pigs. Anatomical T2-weighted images, diffusion kurtosis (DKI) imaging, and T2 relaxometry measures were acquired from a cohort of male guinea pigs from postnatal day (PND) 18–25 (juvenile) to PND 46–51 (adolescent) and PND 118–123 (young adult). Whole-brain diffusion measures revealed the distinct effects of maturation on the microstructural complexity of the male guinea pig brain. Specifically, fractional anisotropy (FA), as well as mean, axial, and radial kurtosis in the corpus callosum, amygdala, dorsal-ventral striatum, and thalamus significantly increased from PND 18–25 to PND 118–123. Age-related alterations in DKI measures within these brain regions paralleled the overall alterations observed in the whole brain. Age-related changes in FA and kurtosis in the gray matter-dominant parietal cerebral cortex and dorsal hippocampus were less pronounced than in the other brain regions. The regional data analysis revealed that between-age changes of diffusion kurtosis metrics were more pronounced than those observed in diffusion tensor metrics. The age-related anatomical differences reported here may be important determinants of the age-dependent neurobehavior of guinea pigs in different tasks.

scholarly journals Continuity and discontinuity in human cortical development and change from embryonic stages to old age

2018 ◽  
Author(s):  
Anders M Fjell ◽  
Chi-Hua Chen ◽  
Donatas Sederevicius ◽  
Markus H Sneve ◽  
Håkon Gryde ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Human Life ◽  
Expression Patterns ◽  
Continuous Process ◽  
Cortical Development ◽  
Brain Regions ◽  
Anterior Cortex ◽  
Human Lifespan ◽  
Clustering Approach ◽  
Anterior Posterior

AbstractThe human cerebral cortex is highly regionalized. We aimed to test whether principles of regionalization could be traced from embryonic development throughout the human lifespan. A data-driven fuzzy-clustering approach was used to identify regions of coordinated longitudinal development of cortical surface area (SA) and thickness (CT) over 1.5 years (n = 301, 4-12 years). First, the SA clusters were compared to patterns from embryonic cortical development. The earliest sign of cortical regionalization is the emergence of morphometric gradients in the cerebral vesicles, with a major gradient running along the anterior-posterior (AP) axis. We found that the principal divide for the developmental SA clusters extended from the inferior-posterior to the superior-anterior cortex, corresponding to the embryonic morphometric AP gradient. Second, embryonic factors showing a clear AP gradient were identified, and tests revealed significant differences in gene expression of these factors between the anterior and posterior clusters. Further, each identified developmental SA and CT cluster showed distinguishable lifespan trajectories in a larger longitudinal dataset (4-88 years, 1633 observations). This means that regions that developed together also changed together throughout life, demonstrating continuity in regionalization of cortical changes. The AP divide in SA development also characterized genetic patterning obtained in an adult twin sample, but otherwise regionalized CT development adhered more to the genetic boundaries. Finally, SA and CT clusters showed differential relationships to cognitive functions. In sum, the results suggest that development of cortical regionalization is a continuous process from the embryonic stage throughout human life.Significance statement (120 words)The protomap and the radial unit theories of brain development have shown that graded expression patterns of several factors are responsible for shaping the ultimately highly partitioned and specialized neocortical landscape. The present study shows that the major anterior-posterior gradient of embryonic development can be detected in the regional cortical expansion profiles of children. The study further demonstrates that brain regions that develop together during childhood also tend to change together throughout the lifespan. This suggests that regional cortical development is a continuous process through the entire life, and that early-life factors have life-long impacts on this process.

scholarly journals Replenishing the Aged Brains: Targeting Oligodendrocytes and Myelination?

2021 ◽  
Vol 13 ◽  
Author(s):  
Xi Zhang ◽  
Nanxin Huang ◽  
Lan Xiao ◽  
Fei Wang ◽  
Tao Li
Keyword(s):  
Brain Function ◽  
Energy Demand ◽  
Functional Decline ◽  
The Elderly ◽  
Major Type ◽  
Brain Functions ◽  
Age Related ◽  
Underlying Mechanisms ◽  
Almost All

Aging affects almost all the aspects of brain functions, but the mechanisms remain largely undefined. Increasing number of literatures have manifested the important role of glial cells in regulating the aging process. Oligodendroglial lineage cell is a major type of glia in central nervous system (CNS), composed of mature oligodendrocytes (OLs), and oligodendroglia precursor cells (OPCs). OLs produce myelin sheaths that insulate axons and provide metabolic support to meet the energy demand. OPCs maintain the population throughout lifetime with the abilities to proliferate and differentiate into OLs. Increasing evidence has shown that oligodendroglial cells display active dynamics in adult and aging CNS, which is extensively involved in age-related brain function decline in the elderly. In this review, we summarized present knowledge about dynamic changes of oligodendroglial lineage cells during normal aging and discussed their potential roles in age-related functional decline. Especially, focused on declined myelinogenesis during aging and underlying mechanisms. Clarifying those oligodendroglial changes and their effects on neurofunctional decline may provide new insights in understanding aging associated brain function declines.

scholarly journals The hedgehog signaling pathway is expressed in the adult mouse hypothalamus and modulated by fasting

2021 ◽  
Author(s):  
Patrick J. Antonellis ◽  
Staci E. Engle ◽  
Kathryn M. Brewer ◽  
Nicolas F. Berbari
Keyword(s):  
Feeding Behavior ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Adult Mouse ◽  
Brain Regions ◽  
Adult Brain ◽  
Hedgehog Pathway ◽  
Transcriptional Level ◽  
Hedgehog Signaling Pathway

The importance of the primary cilium was initially highlighted by the class of human genetic disorders known as ciliopathies. Patients with ciliopathies such as Bardet-Biedl and Alstrom syndrome exhibit hyperphagia-associated obesity as a core clinical phenotype. How primary cilia contribute to energy homeostasis and feeding behavior is complex and unclear, but cilia appear important in both developmental and homeostatic processes. Primary cilia are important signaling centers, required for hedgehog signaling and localization of specific G protein-coupled receptors (GPCRs) with known roles in feeding behavior in mammals. The hedgehog pathway is best known for its role in developmental patterning, but now has recognized roles in adult tissues as well. In the postnatal brain, cilia and hedgehog signaling are important for growth and maintenance of neural progenitors, however, the role of hedgehog signaling in the differentiated adult brain is less clear. Here, we provide a detailed analysis of the expression of core components of the hedgehog signaling pathway in the adult mouse hypothalamus with an emphasis on feeding centers. We show that hedgehog pathway genes continue to be expressed in differentiated neurons important for regulation of feeding behavior. Furthermore, we demonstrate for the first time that pathway activity is regulated at the transcriptional level by fasting. These data suggest that hedgehog signaling is involved in the proper functioning of brain regions which regulate feeding behavior and that hedgehog pathway dysfunction may play a role in the obesity observed in certain ciliopathies.

Flavonoids in the Treatment of Alzheimer’s and Other Neurodegenerative Diseases

2018 ◽  
Vol 25 (27) ◽  
pp. 3228-3246 ◽  
Author(s):  
Cristina Airoldi ◽  
Barbara La Ferla ◽  
Giuseppe D`Orazio ◽  
Carlotta Ciaramelli ◽  
Alessandro Palmioli
Keyword(s):  
Neurodegenerative Diseases ◽  
Biological Activities ◽  
Chemical Properties ◽  
New Drugs ◽  
Terrestrial Plants ◽  
Positive Effects ◽  
Brain Functions ◽  
Age Related ◽  
Physico Chemical ◽  
Almost All

Flavonoids are phytochemicals present in almost all terrestrial plants and, as a consequence, in plant-based foods, and thus consumed by humans through diet. Recent evidences suggest that several flavonoids have positive effects against dementia and Alzheimer’s disease, reversing age-related declines in neurocognitive performances. In this review, we provide a general classification of natural and synthetic flavonoids, a description of their physico-chemical properties, in particular their redox properties and stability, and an extensive overview about their biological activities and structure-activity relationship in the field of neurodegenerative diseases. In addition, a section will be dedicated to the synthetic strategies for the preparation of bioactive derivatives. This information will be essential for the design and development of new drugs that can improve brain functions.

scholarly journals Characterization of GPR101 transcript structure and expression patterns

2016 ◽  
Vol 57 (2) ◽  
pp. 97-111 ◽  
Author(s):  
Giampaolo Trivellin ◽  
Ivana Bjelobaba ◽  
Adrian F Daly ◽  
Darwin O Larco ◽  
Leonor Palmeira ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Adult Life ◽  
Cell Types ◽  
Brain Regions ◽  
Human Tissues ◽  
Specific Expression ◽  
Pituitary Development ◽  
Rapid Amplification ◽  
Almost All ◽  
The Brain

We recently showed that Xq26.3 microduplications cause X-linked acrogigantism (X-LAG). X-LAG patients mainly present with growth hormone and prolactin-secreting adenomas and share a minimal duplicated region containing at least four genes. GPR101 was the only gene highly expressed in their pituitary lesions, but little is known about its expression patterns. In this work, GPR101 transcripts were characterized in human tissues by 5′-Rapid Amplification of cDNA Ends (RACE) and RNAseq, while the putative promoter was bioinformatically predicted. We investigated GPR101 mRNA and protein expression by RT-quantitative PCR (qPCR), whole-mount in situ hybridization, and immunostaining, in human, rhesus monkey, rat and zebrafish. We identified four GPR101 isoforms characterized by different 5′-untranslated regions (UTRs) and a common 6.1kb long 3′UTR. GPR101 expression was very low or absent in almost all adult human tissues examined, except for specific brain regions. Strong GPR101 staining was observed in human fetal pituitary and during adolescence, whereas very weak/absent expression was detected during childhood and adult life. In contrast to humans, adult monkey and rat pituitaries expressed GPR101, but in different cell types. Gpr101 is expressed in the brain and pituitary during rat and zebrafish development; in rat pituitary, Gpr101 is expressed only after birth and shows sexual dimorphism. This study shows that different GPR101 transcripts exist and that the brain is the major site of GPR101 expression across different species, although divergent species- and temporal-specific expression patterns are evident. These findings suggest an important role for GPR101 in brain and pituitary development and likely reflect the very different growth, development and maturation patterns among species.

scholarly journals Spatial and temporal diversity of glycome expression in mammalian brain

2020 ◽  
Vol 117 (46) ◽  
pp. 28743-28753 ◽  
Author(s):  
Jua Lee ◽  
Seungshin Ha ◽  
Minsoo Kim ◽  
Seong-Wook Kim ◽  
Jaekyung Yun ◽  
...  
Keyword(s):  
Large Scale ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Temporal Analysis ◽  
Brain Regions ◽  
Mammalian Brain ◽  
Glycan Structure ◽  
Brain Functions ◽  
Molecular Events ◽  
Glycosylation Pathway

Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale “omics” studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties. Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development. We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse. Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse. We found that glycan expression profiles were dynamically regulated during postnatal developments. A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified. Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development. Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development. Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.

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