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.

Perivascular (Virchow–Robin) spaces

2021 ◽  
pp. 86-89
Keyword(s):  
Blood Vessels ◽  
Shape Change ◽  
Lymphatic Drainage ◽  
Brain Regions ◽  
Mechanical Trauma ◽  
Normal Brain ◽  
Perivascular Spaces ◽  
Mr Images ◽  
Lenticulostriate Artery ◽  
The Brain

Perivascular spaces; also known as the Virchow-Robin Spaces, they are pleurally lined, interstitial fluid-filled areas that surround certain blood vessels in various organs, especially the perforating arteries in the brain, with an immunological function. Dilated perivascular spaces are divided into three types. The first of these is on the lenticulostriate artery, the second is in the cortex following the path of the medullary artery, and the third is in the midbrain. Perivascular spaces can be detected as areas of dilatation on MR images. Although a limited number of perivascular spaces can be seen in a normal brain, the increase in the number of these spaces has been associated with the incidence of various neurodegenerative diseases. Different theories have been suggested about the tendency of the perivascular spaces to expand. Current theories include mechanical trauma due to cerebrospinal fluid pulsing, elongation of penetrating blood vessels, unusual vascular permeability, and increased fluid exudation. In addition, the brain tissue atrophy that occurs with aging; It is thought to contribute to the widening of perivascular spaces by causing shrinkage of arteries, altered arterial wall permeability, obstruction of lymphatic drainage pathways and vascular demyelination. It is assumed that the clinical significance of the dilation tendencies of the perivascular spaces is based on shape change rather than size. These spaces have been mostly observed in brain regions such as corpus callosum, cingulate gyrus, dentate nucleus, substantia nigra and various arterial basins including lenticulostriate artery and mesencephalothalamic artery. In conclusion, when sections are taken on MR imaging, it is possible that perivascular spaces may be confused with microvascular diseases and some neurodegenerative changes. In addition, perivascular spaces can be seen without pathological significance. Therefore, it would be appropriate to investigate the etiological relationship by evaluating the radiological findings and clinical picture together.

scholarly journals Neural Underpinnings of Obesity: The Role of Oxidative Stress and Inflammation in the Brain

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1018
Author(s):  
Caitlyn A. Mullins ◽  
Ritchel B. Gannaban ◽  
Md Shahjalal Khan ◽  
Harsh Shah ◽  
Md Abu B. Siddik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Energy Homeostasis ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Obesity Prevalence ◽  
Beneficial Effects ◽  
The Brain

Obesity prevalence is increasing at an unprecedented rate throughout the world, and is a strong risk factor for metabolic, cardiovascular, and neurological/neurodegenerative disorders. While low-grade systemic inflammation triggered primarily by adipose tissue dysfunction is closely linked to obesity, inflammation is also observed in the brain or the central nervous system (CNS). Considering that the hypothalamus, a classical homeostatic center, and other higher cortical areas (e.g. prefrontal cortex, dorsal striatum, hippocampus, etc.) also actively participate in regulating energy homeostasis by engaging in inhibitory control, reward calculation, and memory retrieval, understanding the role of CNS oxidative stress and inflammation in obesity and their underlying mechanisms would greatly help develop novel therapeutic interventions to correct obesity and related comorbidities. Here we review accumulating evidence for the association between ER stress and mitochondrial dysfunction, the main culprits responsible for oxidative stress and inflammation in various brain regions, and energy imbalance that leads to the development of obesity. Potential beneficial effects of natural antioxidant and anti-inflammatory compounds on CNS health and obesity are also discussed.

Selective Uptake of Hematoporphyrin Derivative into Human Cerebral Glioma

Neurosurgery ◽  
1990 ◽  
Vol 26 (2) ◽  
pp. 248-254 ◽  
Author(s):  
John S. Hill ◽  
Andrew H. Kaye ◽  
William H. Sawyer ◽  
George Morstyn ◽  
Phillip D. Megison ◽  
...  
Keyword(s):  
Low Grade ◽  
Normal Brain ◽  
Hematoporphyrin Derivative ◽  
Cerebral Glioma ◽  
Normal Brain Tissue ◽  
Selective Uptake ◽  
Tumor Region ◽  
Wet Weight ◽  
The Brain ◽  
Adjacent Brain

Abstract The uptake of hematoporphyrin derivative (HpD) into human cerebral glioma was measured using a porphyrin extraction technique. Patients with cerebral glioma were injected with HpD at a dose of 5 mg/kg body weight 24 hours before surgery and photoradiation therapy (PRT). Biopsies of tumor, and where possible, adjacent brain and normal brain were taken for analysis of HpD uptake. HpD was selectively localized into all grades of glioma, and there was a direct correlation between the grade of glioma and HpD level in the tumor. The levels were highest in glioblastoma multiforme (mean uptake of 5.9 mg of HpD/g of tumor wet weight) and lower in the intermediate-grade anaplastic astrocytoma (mean uptake of 2.4 mg/g of tumor) and the low-grade astrocytoma (1.6 mg/g of tumor), Uptake into normal brain tissue taken from HpD-sensitized patients was 0.2 mg/g. HpD was also localized into the “brain adjacent to tumor” region. The selective uptake into the low-grade glioma suggests that PRT may be of use as an adjuvant therapy in these tumors and the detection of HpD in this region indicates that PRT may control the spread of tumor infiltrating into the adjacent normal brain.

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 Long, Noncoding RNA Dysregulation in Glioblastoma

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1604
Author(s):  
Patrick A. DeSouza ◽  
Xuan Qu ◽  
Hao Chen ◽  
Bhuvic Patel ◽  
Christopher A. Maher ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Treatment Resistance ◽  
Normal Brain ◽  
Epigenetic Alterations ◽  
Cellular Processes ◽  
Disease States ◽  
Health And Disease ◽  
The Brain ◽  
Large Repertoire

Transcription occurs across more than 70% of the human genome and more than half of currently annotated genes produce functional noncoding RNAs. Of these transcripts, the majority—long, noncoding RNAs (lncRNAs)—are greater than 200 nucleotides in length and are necessary for various roles in the cell. It is increasingly appreciated that these lncRNAs are relevant in both health and disease states, with the brain expressing the largest number of lncRNAs compared to other organs. Glioblastoma (GBM) is an aggressive, fatal brain tumor that demonstrates remarkable intratumoral heterogeneity, which has made the development of effective therapies challenging. The cooperation between genetic and epigenetic alterations drives rapid adaptation that allows therapeutic evasion and recurrence. Given the large repertoire of lncRNAs in normal brain tissue and the well-described roles of lncRNAs in molecular and cellular processes, these transcripts are important to consider in the context of GBM heterogeneity and treatment resistance. Herein, we review the general mechanisms and biological roles of lncRNAs, with a focus on GBM, as well as RNA-based therapeutics currently in development.

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 Exploration into biomarker potential of region-specific brain gene co-expression networks

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yuqing Hang ◽  
Mohammed Aburidi ◽  
Benafsh Husain ◽  
Allison R. Hickman ◽  
William L. Poehlman ◽  
...  
Keyword(s):  
Brain Region ◽  
Expression Profiles ◽  
Gene Expression Pattern ◽  
Tissue Expression ◽  
Brain Regions ◽  
Normal Brain ◽  
Learning Classifier ◽  
Gene Sets ◽  
Gene Correlation ◽  
The Brain

Abstract The human brain is a complex organ that consists of several regions each with a unique gene expression pattern. Our intent in this study was to construct a gene co-expression network (GCN) for the normal brain using RNA expression profiles from the Genotype-Tissue Expression (GTEx) project. The brain GCN contains gene correlation relationships that are broadly present in the brain or specific to thirteen brain regions, which we later combined into six overarching brain mini-GCNs based on the brain’s structure. Using the expression profiles of brain region-specific GCN edges, we determined how well the brain region samples could be discriminated from each other, visually with t-SNE plots or quantitatively with the Gene Oracle deep learning classifier. Next, we tested these gene sets on their relevance to human tumors of brain and non-brain origin. Interestingly, we found that genes in the six brain mini-GCNs showed markedly higher mutation rates in tumors relative to matched sets of random genes. Further, we found that cortex genes subdivided Head and Neck Squamous Cell Carcinoma (HNSC) tumors and Pheochromocytoma and Paraganglioma (PCPG) tumors into distinct groups. The brain GCN and mini-GCNs are useful resources for the classification of brain regions and identification of biomarker genes for brain related phenotypes.

Repetitive TMS as a Probe of Mood In Health and Disease

CNS Spectrums ◽  
1997 ◽  
Vol 2 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Mark S. George ◽  
Andrew M. Speer ◽  
Eric M. Wassermann ◽  
Timothy A. Kimbrell ◽  
Wendol A. William ◽  
...  
Keyword(s):  
Functional Neuroimaging ◽  
Single Photon ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Photon Emission ◽  
Brain Regions ◽  
Emission Tomography ◽  
Single Photon Emission ◽  
Positron Emission ◽  
Health And Disease ◽  
The Brain

AbstractRecent advances in functional neuroimaging (including positron emission tomography, single-photon emission tomography, and fast magnetic resonance imaging) have allowed better understanding of the brain regions involved in regulating normal and pathological moods. Repetitive transcranial magnetic stimulation (rTMS) has the ability to stimulate or temporarily impair brain regions, which makes it a powerful tool for directly testing theories of the neurologic basis of mood regulation.

scholarly journals Investigating morphological changes in the brain in relation to etiology and duration of olfactory dysfunction with voxel-based morphometry

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
E. M. Postma ◽  
P. A. M. Smeets ◽  
W. M. Boek ◽  
S. Boesveldt
Keyword(s):  
Morphological Changes ◽  
Gray Matter Volume ◽  
Brain Regions ◽  
Olfactory Function ◽  
Voxel Based Morphometry ◽  
Matter Volume ◽  
Olfactory Loss ◽  
Olfactory Input ◽  
The Brain ◽  
Gyrus Rectus

AbstractOlfactory loss (OL) affects up to 20% of the general population and is related to changes in olfaction-related brain regions. This study investigated the effect of etiology and duration of OL on gray matter volume (GMV) of these regions in 257 patients. Voxel-based morphometry was applied to measure GMV in brain regions of interest to test the effects of etiology and duration on regional GMV and the relation between olfactory function and regional GMV. Etiology of OL had a significant effect on GMV in clusters representing the gyrus rectus and orbitofrontal cortex (OFC), bilaterally. Patients with congenital anosmia had reduced GMV in the gyrus rectus and an increased OFC volume compared to patients with acquired OL. There was a significant association between volume of the left OFC and olfactory function. This implies that changes in GMV in patients with acquired OL are mainly reflected in the OFC and depend on olfactory function. Morphology of olfactory areas in the brain therefore seems to relate to olfactory function and the subsequent degree of exposure to olfactory input in patients with acquired OL. Differences in GMV in congenital anosmia are most likely due to the fact that patients were never able to smell.

scholarly journals Genetic, Cellular, and Connectomic Characterization of the Adult Human Brain Regions Commonly Plagued by Glioma

2020 ◽  
Author(s):  
Ayan S. Mandal ◽  
Rafael Romero-Garcia ◽  
Michael G. Hart ◽  
John Suckling
Keyword(s):  
Brain Regions ◽  
Association Cortex ◽  
Low Grade ◽  
Expression Of Genes ◽  
Neuroimaging Data ◽  
Frequency Map ◽  
Multiple Graph ◽  
Anatomic Localization ◽  
The Brain

AbstractA better understanding of the nonrandom localization patterns of gliomas across the brain could lend clues to the origins of these types of tumors. Following hypotheses derived from prior research into neuropsychiatric disease and cancer, gliomas may be expected to localize to brain regions characterized by hubness, stem-like cells, and transcription of genetic drivers of gliomagenesis. We combined neuroimaging data from 335 adult patients with high- and low-grade glioma to form a replicable tumor frequency map. Using this map, we demonstrated that glioma frequency is elevated in association cortex and correlated with multiple graph-theoretical metrics of high functional connectedness. Brain regions populated with stem-like cells also exhibited a high glioma frequency. Furthermore, gliomas were localized to brain regions enriched with the expression of genes associated with chromatin organization and synaptic signaling. Finally, a regression model incorporating connectomic, cellular, and genetic factors explained 58% of the variance in glioma frequency. Our findings illustrate how factors of diverse scale, from genetic to connectomic, can independently influence the anatomic localization of oncogenesis.

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