scholarly journals Epigenetic mechanism of carbohydrate sulfotransferase 3 (CHST3) downregulation in the aging brain

2019 ◽  
Author(s):  
David Baidoe-Ansah ◽  
M Sadman Sakib ◽  
Shaobo Jia ◽  
Andre Fischer ◽  
Rahul Kaushik ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Brain Plasticity ◽  
Epigenetic Mechanism ◽  
Aging Brain ◽  
Chondroitin Sulfates ◽  
Expression Of Genes ◽  
Bona Fide ◽  
Old Mice ◽  
The Brain

AbstractNeural extracellular matrix (ECM) is a complex molecular meshwork surrounding neurons and glial cells in the extracellular space. Structural and functional state of ECM in the brain is tightly regulated by various components of neural ECM such as hyaluronic acid, chondroitin sulfate proteoglycans, link proteins, tenascins, various matrix-modifying enzymes such as chondroitin sulfate synthases and carbohydrate sulfotransferase together with matrix-degrading enzymes. Age-dependent accumulation of ECM molecules is implicated in the age-associated decline in synaptic and cognitive functions. Understanding age-associated changes in the expression of genes involved in regulating various components of ECM can provide an insight into the role of ECM in the aging brain. Hence, in this study, we compared the expression levels of ECM regulating genes in three groups of mice: 2-3 months old mice (2-3M), 22- to 26-month-old mice (22-26M) and more than 30-month-old mice (>30M). Using qPCR, we discovered that in the hippocampus of >30M old mice, the majority of ECM related genes are downregulated, while genes related to neuroinflammation are highly upregulated. This pattern was accompanied by a decrease in cognitive performance of the >30M old mice and was most correlated among ECM-related genes with the downregulation of carbohydrate sulfotransferase 3 (CHST3) gene expression. Interestingly, in 24-26M mice, no general decrease in the expression of ECM related genes was observed, although we still found the upregulation in neuroinflammatory genes and downregulation of CHST3. Further analysis of epigenetic mechanisms revealed a decrease in H3K4me3, three methyl groups at the lysine 4 on the histone H3 proteins, associated with the promoter region of CHST3 gene in non-neuronal (NeuN-negative) but not in neuronal (NeuN-positive) cells. We conclude that in 22-26 M old brains there are minor changes in expression of the studied bona fide neural ECM genes but there is a prominent epigenetic dysregulation of the CHST3 gene responsible for 6-sulfation of chondroitin sulfates, which may lead to impaired brain plasticity and cognitive decline.

scholarly journals 3D Neuronal Mitochondrial Morphology in Axons, Dendrites, and Somata of the Aging Mouse Hippocampus

2021 ◽  
Author(s):  
Julie Faitg ◽  
Clay Lacefield ◽  
Tracey Davey ◽  
Kathryn White ◽  
Ross Laws ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Aging Brain ◽  
Mitochondrial Morphology ◽  
Mitochondrial Network ◽  
Age Related ◽  
Mouse Hippocampus ◽  
Old Mice ◽  
The Brain

The brain′s ability to process complex informations relies on the constant supply of energy through aerobic respiration by mitochondria. Neurons contain three anatomically distinct compartments – the soma, dendrites, and projecting axons – which have different energetic and biochemical requirements, as well as different mitochondrial morphologies in cultured systems. Here we apply a quantitative three-dimensional electron microscopy approach to map mitochondrial network morphology and complexity in the mouse brain. We examine three neuronal sub–compartments – the soma, dendrites, myelinated axons – in the dentate gyrus and CA1 of the mouse hippocampus, two subregions with distinct principal cell types and functions. We also establish compartment-specific differences in mitochondrial morphology across these cell types between young and old mice, highlighting differences in age-related morphological recalibrations. Overall, these data define the nature of the neuronal mitochondrial network in the mouse hippocampus, providing a foundation to examine the role of mitochondrial morpho–function in the aging brain.

scholarly journals Epigenetic mechanisms in sexual differentiation of the brain and behaviour

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150114 ◽  
Author(s):  
Nancy G. Forger
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Sexual Differentiation ◽  
Wide Distribution ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanism ◽  
Epigenetic Mechanisms ◽  
Genome Wide ◽  
The Brain

Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour.

scholarly journals Identification of Novel Roles of the Cytochrome P450 System in Early Embryogenesis: Effects on Vasculogenesis and Retinoic Acid Homeostasis

2003 ◽  
Vol 23 (17) ◽  
pp. 6103-6116 ◽  
Author(s):  
Diana M. E. Otto ◽  
Colin J. Henderson ◽  
Dianne Carrie ◽  
Megan Davey ◽  
Thomas E. Gundersen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Retinoic Acid ◽  
Cell Types ◽  
Monooxygenase System ◽  
Cytochrome P450 System ◽  
Expression Of Genes ◽  
Close Relationship ◽  
Metabolism Of Xenobiotics ◽  
The Brain

ABSTRACT The cytochrome P450-dependent monooxygenase system catalyzes the metabolism of xenobiotics and endogenous compounds, including hormones and retinoic acid. In order to establish the role of these enzymes in embryogenesis, we have inactivated the system through the deletion of the gene for the electron donor to all microsomal P450 proteins, cytochrome P450 reductase (Cpr). Mouse embryos homozygous for this deletion died in early to middle gestation (∼9.5 days postcoitum [dpc]) and exhibited a number of novel phenotypes, including the severe inhibition of vasculogenesis and hematopoiesis. In addition, defects in the brain, limbs, and cell types where CPR was shown to be expressed were observed. Some of the observed abnormalities have been associated with perturbations in retinoic acid homeostasis in later embryogenesis. Consistent with this possibility, embryos at 9.5 dpc had significantly elevated levels of retinoic acid and reduced levels of retinol. Further, some of the observed phenotypes could be either reversed or exacerbated by decreasing or increasing maternal retinoic acid exposure, respectively. Detailed analysis demonstrated a close relationship between the observed phenotype and the expression of genes controlling vasculogenesis. These data demonstrate that the cytochrome P450 system plays a key role in early embryonic development; this process appears to be, at least in part, controlled by regional concentrations of retinoic acid and has profound effects on blood vessel formation.

scholarly journals Changes in expression of GFAP, ApoE and APP mRNA and protein levels in the adult rat brain following cortical injury

2013 ◽  
Vol 65 (1) ◽  
pp. 255-264
Author(s):  
Natasa Loncarevic-Vasiljkovic ◽  
Vesna Pesic ◽  
N. Tanic ◽  
Desanka Milanovic ◽  
Aleksandra Mladenovic-Djordjevic ◽  
...  
Keyword(s):  
Brain Plasticity ◽  
Recovery Period ◽  
Potential Contribution ◽  
Cortical Injury ◽  
Adult Rat ◽  
Protein Levels ◽  
Adult Rat Brain ◽  
Apoe Protein ◽  
The Brain

The recovery period following cortical injury (CI) is characterized by a dynamic and highly complex interplay between beneficial and detrimental events. The aim of this study was to examine the expressions of Glial Fibrillary Acidic Protein (GFAP), Apolipoprotein E (ApoE) and Amyloid Precursor Protein (APP), all of which are involved in brain plasticity and neurodegeneration. Our results reveal that CI strongly influenced GFAP, ApoE and APP mRNA expression, as well as GFAP and ApoE protein expression. Considering the pivotal role of these proteins in the brain, the obtained results point to their potential contribution in neurodegeneration and consequent Alzheimer?s disease development.

scholarly journals Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders

2021 ◽  
Vol 22 (19) ◽  
pp. 10251
Author(s):  
Vladimir Sukhorukov ◽  
Dmitry Voronkov ◽  
Tatiana Baranich ◽  
Natalia Mudzhiri ◽  
Alina Magnaeva ◽  
...  
Keyword(s):  
Glial Cells ◽  
Brain Aging ◽  
Cellular Level ◽  
Aging Brain ◽  
The Past ◽  
Age Related ◽  
Accumulation Of Damage ◽  
Quantity Control ◽  
The Brain

Aging is associated with a decline in cognitive function, which can partly be explained by the accumulation of damage to the brain cells over time. Neurons and glia undergo morphological and ultrastructure changes during aging. Over the past several years, it has become evident that at the cellular level, various hallmarks of an aging brain are closely related to mitophagy. The importance of mitochondria quality and quantity control through mitophagy is highlighted by the contribution that defects in mitochondria–autophagy crosstalk make to aging and age-related diseases. In this review, we analyze some of the more recent findings regarding the study of brain aging and neurodegeneration in the context of mitophagy. We discuss the data on the dynamics of selective autophagy in neurons and glial cells during aging and in the course of neurodegeneration, focusing on three mechanisms of mitophagy: non-receptor-mediated mitophagy, receptor-mediated mitophagy, and transcellular mitophagy. We review the role of mitophagy in neuronal/glial homeostasis and in the molecular pathogenesis of neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, and other disorders. Common mechanisms of aging and neurodegeneration that are related to different mitophagy pathways provide a number of promising targets for potential therapeutic agents.

scholarly journals Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter

2018 ◽  
Author(s):  
Miho Sato-Hashimoto ◽  
Tomomi Nozu ◽  
Riho Toriba ◽  
Ayano Horikoshi ◽  
Miho Akaike ◽  
...  
Keyword(s):  
White Matter ◽  
Membrane Protein ◽  
Functional Role ◽  
Regulatory Protein ◽  
Genetic Ablation ◽  
Brain White Matter ◽  
Expression Of Genes ◽  
The Brain ◽  
Repair Phase

AbstractA characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein α (SIRPα), a membrane protein, induced CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRPα, and microglia-specific SIRPα knockout mice exhibited the same phenotype, suggesting the interaction between microglial SIRPα and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPα did not cause detectable damage in the white matter, but resulted in the increased expression of genes characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.

scholarly journals Possible Epigenetic Role of Vitexin in Regulating Neuroinflammation in Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
M. A. F. Yahaya ◽  
S. Z. I. Zolkiffly ◽  
M. A. M. Moklas ◽  
H. Abdul Hamid ◽  
J. Stanslas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Epigenetic Mechanism ◽  
Pharmacological Properties ◽  
Progressive Degeneration ◽  
Severity Of The Disease ◽  
The Brain ◽  
Anti Inflammation

Alzheimer’s disease (AD) has been clinically characterized by a progressive degeneration of neurons which resulted in a gradual and irreversible cognitive impairment. The accumulation of Aβ and τ proteins in the brain contribute to the severity of the disease. Recently, vitexin compound has been the talk amongst researchers due to its pharmacological properties as anti-inflammation and anti-AD. However, the epigenetic mechanism of the compound in regulating the neuroinflammation activity is yet to be fully elucidated. Hence, this review discusses the potential of vitexin compound to have the pharmacoepigenetic property in regulating the neuroinflammation activity in relation to AD. It is with hope that the review would unveil the potential of vitexin as the candidate in treating AD.

scholarly journals Autism-like syndrome is induced by pharmacological suppression of BET proteins in young mice

2015 ◽  
Vol 212 (11) ◽  
pp. 1771-1781 ◽  
Author(s):  
Josefa M. Sullivan ◽  
Ana Badimon ◽  
Uwe Schaefer ◽  
Pinar Ayata ◽  
James Gray ◽  
...  
Keyword(s):  
Target Genes ◽  
Autism Spectrum ◽  
Epigenetic Mechanism ◽  
The Novel ◽  
Neuronal Gene ◽  
Novel Therapeutic Strategies ◽  
The Brain ◽  
Epigenetic Processes ◽  
Young Mice

Studies investigating the causes of autism spectrum disorder (ASD) point to genetic, as well as epigenetic, mechanisms of the disease. Identification of epigenetic processes that contribute to ASD development and progression is of major importance and may lead to the development of novel therapeutic strategies. Here, we identify the bromodomain and extraterminal domain–containing proteins (BETs) as epigenetic regulators of genes involved in ASD-like behaviors in mice. We found that the pharmacological suppression of BET proteins in the brain of young mice, by the novel, highly specific, brain-permeable inhibitor I-BET858 leads to selective suppression of neuronal gene expression followed by the development of an autism-like syndrome. Many of the I-BET858–affected genes have been linked to ASD in humans, thus suggesting the key role of the BET-controlled gene network in the disorder. Our studies suggest that environmental factors controlling BET proteins or their target genes may contribute to the epigenetic mechanism of ASD.

scholarly journals Some contributions from Neurosciences to Education: do enriched environments increase the learning capacity of our brain?

2021 ◽  
Vol 3 (2) ◽  
pp. 25-39
Author(s):  
Luís Calafate ◽  
◽  
Sara Calafate ◽  
Keyword(s):  
Brain Plasticity ◽  
Current Debate ◽  
Genetic Inheritance ◽  
Functional Changes ◽  
Learning Capacity ◽  
Enriched Environments ◽  
The One ◽  
External Stimuli ◽  
The Brain

The reflection and discussion on the role of genetic specification and experience in the acquisition of a function and in the development of an individual reflects a fascinating and very current debate among those working in the area of behavior and development. Concerning the development of human behavior and the influence of biological heritage and the envitonment, conflicting and sometimes exclusive positions were established. On the one hand, adherents of genetic inheritance exclude the possibility of the influence of the environment. On the other hand, supporters of the environment exclude genetic inheritance. There is also an eclectic position, reconciling both extremes. Furthermore, within the scope of the trends themselves, differentiating nuances emerge. It is therefore, a very controversial subject to which we dedicate this work from a Neuroscience perspective. We will approach brain neuroplasticity as the ability of the nervous system to change and adapt, in response to internal and external stimuli, including structural and / or functional changes throughout life. Brain plasticity is one of the pillars of learning and memory processes. In short, the role of Neurosciences in the field of Educational Sciences is taking shape and the concept of neuroplasticity is a sine qua non condition for trying to establish a connection between education, behavior and the brain.

scholarly journals Aspirin treatment does not increase microhemorrhage size in young or aged mice

2018 ◽  
Author(s):  
Sandy Chan ◽  
Morgan Brophy ◽  
Nozomi Nishimura ◽  
Chris B. Schaffer
Keyword(s):  
Femtosecond Laser Ablation ◽  
Surrounding Tissue ◽  
Aging Brain ◽  
Older Individuals ◽  
Aged Mice ◽  
Intravenous Heparin ◽  
The Impact ◽  
Old Mice ◽  
The Brain ◽  
Vessel Rupture

AbstractMicrohemorrhages are common in the aging brain and are thought to contribute to cognitive decline and the development of neurodegenerative diseases, such as Alzheimer’s disease. Chronic aspirin therapy is widespread in older individuals and decreases the risk of coronary artery occlusions and stroke. There remains a concern that such aspirin usage may prolong bleeding after a vessel rupture in the brain, leading to larger bleeds that cause more damage to the surrounding tissue. Here, we aimed to understand the influence of aspirin usage on the size of cortical microhemorrhages and explored the impact of age. We used femtosecond laser ablation to rupture arterioles in the cortex of both young (2-5 months old) and aged (18-29 months old) mice dosed on aspirin in their drinking water and measured the extent of penetration of both red blood cells and blood plasma into the surrounding tissue. We found no difference in microhemorrhage size for both young and aged mice dosed on aspirin, as compared to controls (hematoma diameter = 104 +/- 39 (97 +/- 38) μm in controls and 109 +/- 25 (101 +/- 28) μm in aspirin-treated young (aged) mice; mean +/- SD). In contrast, young mice treated with intravenous heparin had an increased hematoma diameter of 136 +/- 44 μm. These data suggest that aspirin does not increase the size of microhemorrhages, supporting the safety of aspirin usage.

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