scholarly journals Gene expression changes in the course of normal brain aging are sexually dimorphic

2008 ◽  
Vol 105 (40) ◽  
pp. 15605-15610 ◽  
Author(s):  
Nicole C. Berchtold ◽  
David H. Cribbs ◽  
Paul D. Coleman ◽  
Joseph Rogers ◽  
Elizabeth Head ◽  
...  
Keyword(s):  
Gene Expression ◽  
Entorhinal Cortex ◽  
Brain Aging ◽  
Expression Profiles ◽  
Later Life ◽  
Normal Brain ◽  
Sexually Dimorphic ◽  
Compensatory Mechanisms ◽  
Superior Frontal Gyrus ◽  
The Brain

Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact individuals aged 20–99 years. Perspectives on global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age in the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the sixth to seventh decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with down-regulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with proportionally greater activation in the female brain. These data open opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain and suggest that this balance is set differently in males and females, an intriguing idea.

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 Resilience, plasticity and robustness in gene expression during aging in the brain of outbred deer mice

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
E Soltanmohammadi ◽  
Y Zhang ◽  
I Chatzistamou ◽  
H. Kiaris
Keyword(s):  
Gene Expression ◽  
Cholesterol Metabolism ◽  
Expression Profiles ◽  
Deer Mice ◽  
Abrupt Changes ◽  
Transcriptional Changes ◽  
Thrombospondin 4 ◽  
Whole Transcriptome ◽  
The Brain ◽  
Shed Light

Abstract Background Genes that belong to the same network are frequently co-expressed, but collectively, how the coordination of the whole transcriptome is perturbed during aging remains unclear. To explore this, we calculated the correlation of each gene in the transcriptome with every other, in the brain of young and older outbred deer mice (P. leucopus and P. maniculatus). Results In about 25 % of the genes, coordination was inversed during aging. Gene Ontology analysis in both species, for the genes that exhibited inverse transcriptomic coordination during aging pointed to alterations in the perception of smell, a known impairment occurring during aging. In P. leucopus, alterations in genes related to cholesterol metabolism were also identified. Among the genes that exhibited the most pronounced inversion in their coordination profiles during aging was THBS4, that encodes for thrombospondin-4, a protein that was recently identified as rejuvenation factor in mice. Relatively to its breadth, abolishment of coordination was more prominent in the long-living P. leucopus than in P. maniculatus but in the latter, the intensity of de-coordination was higher. Conclusions There sults suggest that aging is associated with more stringent retention of expression profiles for some genes and more abrupt changes in others, while more subtle but widespread changes in gene expression appear protective. Our findings shed light in the mode of the transcriptional changes occurring in the brain during aging and suggest that strategies aiming to broader but more modest changes in gene expression may be preferrable to correct aging-associated deregulation in gene expression.

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

Ca2+ regulation and gene expression in normal brain aging

2004 ◽  
Vol 27 (10) ◽  
pp. 614-620 ◽  
Author(s):  
Emil C. Toescu ◽  
Alexei Verkhratsky ◽  
Philip W. Landfield
Keyword(s):  
Gene Expression ◽  
Brain Aging ◽  
Normal Brain

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.

Effect of pharmacologic resuscitation on the brain gene expression profiles in a swine model of traumatic brain injury and hemorrhage

2014 ◽  
Vol 77 (6) ◽  
pp. 906-912 ◽  
Author(s):  
Simone E. Dekker ◽  
Ted Bambakidis ◽  
Martin Sillesen ◽  
Baoling Liu ◽  
Craig N. Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Swine Model ◽  
Brain Gene Expression ◽  
The Brain

scholarly journals Systems Biology Analysis of the Antagonizing Effects of HIV-1 Tat Expression in the Brain over Transcriptional Changes Caused by Methamphetamine Sensitization

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 426 ◽  
Author(s):  
Liana V. Basova ◽  
James P. Kesby ◽  
Marcus Kaul ◽  
Svetlana Semenova ◽  
Maria Cecilia Garibaldi Marcondes
Keyword(s):  
Gene Expression ◽  
Systems Biology ◽  
Gene Transcription ◽  
Gene Networks ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Sirtuin 1 ◽  
The Brain ◽  
Hiv 1

Methamphetamine (Meth) abuse is common among humans with immunodeficiency virus (HIV). The HIV-1 regulatory protein, trans-activator of transcription (Tat), has been described to induce changes in brain gene transcription that can result in impaired reward circuitry, as well as in inflammatory processes. In transgenic mice with doxycycline-induced Tat protein expression in the brain, i.e., a mouse model of neuroHIV, we tested global gene expression patterns induced by Meth sensitization. Meth-induced locomotor sensitization included repeated daily Meth or saline injections for seven days and Meth challenge after a seven-day abstinence period. Brain samples were collected 30 min after the Meth challenge. We investigated global gene expression changes in the caudate putamen, an area with relevance in behavior and HIV pathogenesis, and performed pathway and transcriptional factor usage predictions using systems biology strategies. We found that Tat expression alone had a very limited impact in gene transcription after the Meth challenge. In contrast, Meth-induced sensitization in the absence of Tat induced a global suppression of gene transcription. Interestingly, the interaction between Tat and Meth broadly prevented the Meth-induced global transcriptional suppression, by maintaining regulation pathways, and resulting in gene expression profiles that were more similar to the controls. Pathways associated with mitochondrial health, initiation of transcription and translation, as well as with epigenetic control, were heavily affected by Meth, and by its interaction with Tat in anti-directional ways. A series of systems strategies have predicted several components impacted by these interactions, including mitochondrial pathways, mTOR/RICTOR, AP-1 transcription factor, and eukaryotic initiation factors involved in transcription and translation. In spite of the antagonizing effects of Tat, a few genes identified in relevant gene networks remained downregulated, such as sirtuin 1, and the amyloid precursor protein (APP). In conclusion, Tat expression in the brain had a low acute transcriptional impact but strongly interacted with Meth sensitization, to modify effects in the global transcriptome.

Gene Expression Profiles of Entorhinal Cortex in Alzheimer’s Disease

2014 ◽  
Vol 29 (6) ◽  
pp. 526-532 ◽  
Author(s):  
Bingqian Ding ◽  
Yan Xi ◽  
Ming Gao ◽  
Zhenjiang Li ◽  
Chenyang Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Entorhinal Cortex ◽  
Expression Profiles ◽  
Gene Expression Profiles

scholarly journals Analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the brain

2014 ◽  
Vol 33 (4) ◽  
pp. 887-896 ◽  
Author(s):  
MOMOKO YOSHIDA ◽  
YUKO WATANABE ◽  
KYOSUKE YAMANISHI ◽  
AKIFUMI YAMASHITA ◽  
HIDEYUKI YAMAMOTO ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spontaneously Hypertensive Rats ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
The Brain

scholarly journals The Emerging Role of the Interplay Among Astrocytes, Microglia, and Neurons in the Hippocampus in Health and Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Daniele Lana ◽  
Filippo Ugolini ◽  
Daniele Nosi ◽  
Gary L. Wenk ◽  
Maria Grazia Giovannini
Keyword(s):  
Acute Inflammation ◽  
Brain Aging ◽  
Morphological Changes ◽  
Brain Regions ◽  
Stratum Radiatum ◽  
Low Grade ◽  
Normal Brain ◽  
Chronic Inflammatory Response ◽  
Health And Disease ◽  
The Brain

For over a century, neurons have been considered the basic functional units of the brain while glia only elements of support. Activation of glia has been long regarded detrimental for survival of neurons but more it appears that this is not the case in all circumstances. In this review, we report and discuss the recent literature on the alterations of astrocytes and microglia during inflammaging, the low-grade, slow, chronic inflammatory response that characterizes normal brain aging, and in acute inflammation. Becoming reactive, astrocytes and microglia undergo transcriptional, functional, and morphological changes that transform them into cells with different properties and functions, such as A1 and A2 astrocytes, and M1 and M2 microglia. This classification of microglia and astrocytes in two different, all-or-none states seems too simplistic, and does not correspond to the diverse variety of phenotypes so far found in the brain. Different interactions occur among the many cell populations of the central nervous system in health and disease conditions. Such interactions give rise to networks of morphological and functional reciprocal reliance and dependency. Alterations affecting one cell population reverberate to the others, favoring or dysregulating their activities. In the last part of this review, we present the modifications of the interplay between neurons and glia in rat models of brain aging and acute inflammation, focusing on the differences between CA1 and CA3 areas of the hippocampus, one of the brain regions most susceptible to different insults. With triple labeling fluorescent immunohistochemistry and confocal microscopy (TIC), it is possible to evaluate and compare quantitatively the morphological and functional alterations of the components of the neuron-astrocyte-microglia triad. In the contiguous and interconnected regions of rat hippocampus, CA1 and CA3 Stratum Radiatum, astrocytes and microglia show a different, finely regulated, and region-specific reactivity, demonstrating that glia responses vary in a significant manner from area to area. It will be of great interest to verify whether these differential reactivities of glia explain the diverse vulnerability of the hippocampal areas to aging or to different damaging insults, and particularly the higher sensitivity of CA1 pyramidal neurons to inflammatory stimuli.

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