scholarly journals The Roles of Exosomes as Future Therapeutic Agents and Diagnostic Tools for Glioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoben Wu ◽  
Xingbang Wang ◽  
Jing Wang ◽  
Yingying Hao ◽  
Fang Liu ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Current Knowledge ◽  
Therapeutic Agents ◽  
Common Type ◽  
Brain Diseases ◽  
Diagnostic Tools ◽  
Potential Candidate ◽  
Brain Glioma ◽  
Supporting Cells ◽  
The Brain

Glioma is a common type of tumor originating in the brain. Glioma develops in the gluey supporting cells (glial cells) that surround and support nerve cells. Exosomes are extracellular vesicles that contain microRNAs, messenger RNA, and proteins. Exosomes are the most prominent mediators of intercellular communication, regulating, instructing, and re-educating their surrounding milieu targeting different organs. As exosomes’ diameter is in the nano range, the ability to cross the blood–brain barrier, a crucial obstacle in developing therapeutics against brain diseases, including glioma, makes the exosomes a potential candidate for delivering therapeutic agents for targeting malignant glioma. This review communicates the current knowledge of exosomes’ significant roles that make them crucial future therapeutic agents and diagnostic tools for glioma.

scholarly journals Physical Activity vs. Redox Balance in the Brain: Brain Health, Aging and Diseases

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 95
Author(s):  
Paweł Sutkowy ◽  
Alina Woźniak ◽  
Celestyna Mila-Kierzenkowska ◽  
Karolina Szewczyk-Golec ◽  
Roland Wesołowski ◽  
...  
Keyword(s):  
Physical Activity ◽  
Physical Exercise ◽  
Current Knowledge ◽  
Redox Balance ◽  
Brain Diseases ◽  
Antidepressant Effect ◽  
Brain Health ◽  
Health Aging ◽  
The Impact ◽  
The Brain

It has been proven that physical exercise improves cognitive function and memory, has an analgesic and antidepressant effect, and delays the aging of the brain and the development of diseases, including neurodegenerative disorders. There are even attempts to use physical activity in the treatment of mental diseases. The course of most diseases is strictly associated with oxidative stress, which can be prevented or alleviated with regular exercise. It has been proven that physical exercise helps to maintain the oxidant–antioxidant balance. In this review, we present the current knowledge on redox balance in the organism and the consequences of its disruption, while focusing mainly on the brain. Furthermore, we discuss the impact of physical activity on aging and brain diseases, and present current recommendations and directions for further research in this area.

scholarly journals Statins and the Brain: More than Lipid Lowering Agents?

2018 ◽  
Vol 17 (1) ◽  
pp. 59-83 ◽  
Author(s):  
Anna Fracassi ◽  
Martina Marangoni ◽  
Pamela Rosso ◽  
Valentina Pallottini ◽  
Marco Fioramonti ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Current Knowledge ◽  
Biological Activities ◽  
Scientific Information ◽  
Brain Diseases ◽  
Lipid Lowering ◽  
Mva Pathway ◽  
Pubmed Database ◽  
The Brain

Background: Statins represent a class of medications widely prescribed to efficiently treat dyslipidemia. These drugs inhibit 3-βhydroxy 3β-methylglutaryl Coenzyme A reductase (HMGR), the rate-limiting enzyme of mevalonate (MVA) pathway. Besides cholesterol, MVA pathway leads to the production of several other compounds, which are essential in the regulation of a plethora of biological activities, including in the central nervous system. For these reasons, statins are able to induce pleiotropic actions, and acquire increased interest as potential and novel modulators in brain processes, especially during pathological conditions. </P><P> Objective: The purpose of this review is to summarize and examine the current knowledge about pharmacokinetic and pharmacodynamic properties of statins in the brain. In addition, effects of statin on brain diseases are discussed providing the most up-to-date information. </P><P> Methods: Relevant scientific information was identified from PubMed database using the following keywords: statins and brain, central nervous system, neurological diseases, neurodegeneration, brain tumors, mood, stroke. </P><P> Results: 315 scientific articles were selected and analyzed for the writing of this review article. Several papers highlighted that statin treatment is effective in preventing or ameliorating the symptomatology of a number of brain pathologies. However, other studies failed to demonstrate a neuroprotective effect. Conclusion: Even though considerable research studies suggest pivotal functional outcomes induced by statin therapy, additional investigation is required to better determine the pharmacological effectiveness of statins in the brain, and support their clinical use in the management of different neuropathologies.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

Experimental Rodent Models of Vascular Dementia: A Systematic Review

2021 ◽  
Vol 19 ◽  
Author(s):  
Nidhi Tiwari ◽  
Jyoti Upadhyay ◽  
Mohd Nazam Ansari ◽  
Syed Shadab Raza ◽  
Wasim Ahmad ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Small Vessel Disease ◽  
Current Knowledge ◽  
Vascular Cognitive Impairment ◽  
Experimental Models ◽  
New Drugs ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
The Brain ◽  
Large Vessel Disease

: Vascular dementia (VaD) occurs due to cerebrovascular insufficiency, which leads to decreased blood circulation to the brain, thereby resulting in mental disabilities. The main causes of vascular cognitive impairment (VCI) are severe hypoperfusion, stroke, hypertension, large vessel disease (cortical), small vessel disease (subcortical VaD), strategic infarct, hemorrhage (microbleed), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and cerebral amyloid angiopathy (CAA),which leads to decreased cerebrovascular perfusion. Many metabolic disorders such as diabetes mellitus (DM), dyslipidemia, and hyperhomocysteinemia are also related to VaD. The rodent experimental models provide a better prospective for the investigation of the molecular mechanism of new drugs. A plethora of experimental models are available that mimic the pathological conditions and lead to VaD. This review article updates the current knowledge on the basis of VaD, risk factors, pathophysiology, mechanism, advantages, limitations, and the modification of various available rodent experimental models.

scholarly journals L2HGDH Missense Variant in a Cat with L-2-Hydroxyglutaric Aciduria

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 682
Author(s):  
Matthias Christen ◽  
Nils Janzen ◽  
Anne Fraser ◽  
Adrian C. Sewell ◽  
Vidhya Jagannathan ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Genetic Defect ◽  
Clinical Signs ◽  
Missense Variant ◽  
Microcytic Anemia ◽  
Abnormal Behavior ◽  
Functional Candidate Gene ◽  
History Of ◽  
The Brain ◽  
Hydroxyglutaric Acid

A 7-month-old, spayed female, domestic longhair cat with L-2-hydroxyglutaric aciduria (L-2-HGA) was investigated. The aim of this study was to investigate the clinical signs, metabolic changes and underlying genetic defect. The owner of the cat reported a 4-month history of multiple paroxysmal seizure-like episodes, characterized by running around the house, often in circles, with abnormal behavior, bumping into obstacles, salivating and often urinating. The episodes were followed by a period of disorientation and inappetence. Neurological examination revealed an absent bilateral menace response. Routine blood work revealed mild microcytic anemia but biochemistry, ammonia, lactate and pre- and post-prandial bile acids were unremarkable. MRI of the brain identified multifocal, bilaterally symmetrical and T2-weighted hyperintensities within the prosencephalon, mesencephalon and metencephalon, primarily affecting the grey matter. Urinary organic acids identified highly increased levels of L-2-hydroxyglutaric acid. The cat was treated with the anticonvulsants levetiracetam and phenobarbitone and has been seizure-free for 16 months. We sequenced the genome of the affected cat and compared the data to 48 control genomes. L2HGDH, coding for L-2-hydroxyglutarate dehydrogenase, was investigated as the top functional candidate gene. This search revealed a single private protein-changing variant in the affected cat. The identified homozygous variant, XM_023255678.1:c.1301A>G, is predicted to result in an amino acid change in the L2HGDH protein, XP_023111446.1:p.His434Arg. The available clinical and biochemical data together with current knowledge about L2HGDH variants and their functional impact in humans and dogs allow us to classify the p.His434Arg variant as a causative variant for the observed neurological signs in this cat.

A new method to predict anomaly in brain network based on graph deep learning

2020 ◽  
Vol 31 (6) ◽  
pp. 681-689
Author(s):  
Jalal Mirakhorli ◽  
Hamidreza Amindavar ◽  
Mojgan Mirakhorli
Keyword(s):  
Deep Learning ◽  
Large Scale ◽  
Brain Plasticity ◽  
Brain Network ◽  
High Order ◽  
Brain Diseases ◽  
Simultaneous Occurrence ◽  
Generative Adversarial Network ◽  
The Brain ◽  
Brain Connections

AbstractFunctional magnetic resonance imaging a neuroimaging technique which is used in brain disorders and dysfunction studies, has been improved in recent years by mapping the topology of the brain connections, named connectopic mapping. Based on the fact that healthy and unhealthy brain regions and functions differ slightly, studying the complex topology of the functional and structural networks in the human brain is too complicated considering the growth of evaluation measures. One of the applications of irregular graph deep learning is to analyze the human cognitive functions related to the gene expression and related distributed spatial patterns. Since a variety of brain solutions can be dynamically held in the neuronal networks of the brain with different activity patterns and functional connectivity, both node-centric and graph-centric tasks are involved in this application. In this study, we used an individual generative model and high order graph analysis for the region of interest recognition areas of the brain with abnormal connection during performing certain tasks and resting-state or decompose irregular observations. Accordingly, a high order framework of Variational Graph Autoencoder with a Gaussian distributer was proposed in the paper to analyze the functional data in brain imaging studies in which Generative Adversarial Network is employed for optimizing the latent space in the process of learning strong non-rigid graphs among large scale data. Furthermore, the possible modes of correlations were distinguished in abnormal brain connections. Our goal was to find the degree of correlation between the affected regions and their simultaneous occurrence over time. We can take advantage of this to diagnose brain diseases or show the ability of the nervous system to modify brain topology at all angles and brain plasticity according to input stimuli. In this study, we particularly focused on Alzheimer’s disease.

scholarly journals The L1-dependant and Pol III transcribed Alu retrotransposon, from its discovery to innate immunity

2021 ◽  
Vol 48 (3) ◽  
pp. 2775-2789
Author(s):  
Ludwig Stenz
Keyword(s):  
Human Genome ◽  
Viral Infections ◽  
De Novo ◽  
Current Knowledge ◽  
Innate Immune ◽  
De Novo Mutation ◽  
Neuronal Diversity ◽  
Alu Sequences ◽  
Pol Iii ◽  
The Brain

AbstractThe 300 bp dimeric repeats digestible by AluI were discovered in 1979. Since then, Alu were involved in the most fundamental epigenetic mechanisms, namely reprogramming, pluripotency, imprinting and mosaicism. These Alu encode a family of retrotransposons transcribed by the RNA Pol III machinery, notably when the cytosines that constitute their sequences are de-methylated. Then, Alu hijack the functions of ORF2 encoded by another transposons named L1 during reverse transcription and integration into new sites. That mechanism functions as a complex genetic parasite able to copy-paste Alu sequences. Doing that, Alu have modified even the size of the human genome, as well as of other primate genomes, during 65 million years of co-evolution. Actually, one germline retro-transposition still occurs each 20 births. Thus, Alu continue to modify our human genome nowadays and were implicated in de novo mutation causing diseases including deletions, duplications and rearrangements. Most recently, retrotransposons were found to trigger neuronal diversity by inducing mosaicism in the brain. Finally, boosted during viral infections, Alu clearly interact with the innate immune system. The purpose of that review is to give a condensed overview of all these major findings that concern the fascinating physiology of Alu from their discovery up to the current knowledge.

scholarly journals Genomic Mosaicism Formed by Somatic Variation in the Aging and Diseased Brain

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1071
Author(s):  
Isabel Costantino ◽  
Juliet Nicodemus ◽  
Jerold Chun
Keyword(s):  
Dna Sequence ◽  
Technology Development ◽  
Copy Number Variations ◽  
Brain Cell ◽  
Brain Diseases ◽  
Multiple Forms ◽  
Somatic Variation ◽  
Dna Content Variation ◽  
Effects Of Aging ◽  
The Brain

Over the past 20 years, analyses of single brain cell genomes have revealed that the brain is composed of cells with myriad distinct genomes: the brain is a genomic mosaic, generated by a host of DNA sequence-altering processes that occur somatically and do not affect the germline. As such, these sequence changes are not heritable. Some processes appear to occur during neurogenesis, when cells are mitotic, whereas others may also function in post-mitotic cells. Here, we review multiple forms of DNA sequence alterations that have now been documented: aneuploidies and aneusomies, smaller copy number variations (CNVs), somatic repeat expansions, retrotransposons, genomic cDNAs (gencDNAs) associated with somatic gene recombination (SGR), and single nucleotide variations (SNVs). A catch-all term of DNA content variation (DCV) has also been used to describe the overall phenomenon, which can include multiple forms within a single cell’s genome. A requisite step in the analyses of genomic mosaicism is ongoing technology development, which is also discussed. Genomic mosaicism alters one of the most stable biological molecules, DNA, which may have many repercussions, ranging from normal functions including effects of aging, to creating dysfunction that occurs in neurodegenerative and other brain diseases, most of which show sporadic presentation, unlinked to causal, heritable genes.

scholarly journals Human Monocytes Plasticity in Neurodegeneration

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 717
Author(s):  
Ilenia Savinetti ◽  
Angela Papagna ◽  
Maria Foti
Keyword(s):  
Neurodegenerative Disorders ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Surface Marker ◽  
First Line ◽  
Surface Marker Expression ◽  
Physiological Properties ◽  
Attractive Therapeutic Target ◽  
The Brain ◽  
Lateral Sclerosis

Monocytes play a crucial role in immunity and tissue homeostasis. They constitute the first line of defense during the inflammatory process, playing a role in the pathogenesis and progression of diseases, making them an attractive therapeutic target. They are heterogeneous in morphology and surface marker expression, which suggest different molecular and physiological properties. Recent evidences have demonstrated their ability to enter the brain, and, as a consequence, their hypothetical role in different neurodegenerative diseases. In this review, we will discuss the current knowledge about the correlation between monocyte dysregulation in the brain and/or in the periphery and neurological diseases in humans. Here we will focus on the most common neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis.

HISTOLOGY AND HISTOCHEMISTRY OF THE PINEAL ORGAN IN THE SOCKEYE SALMON, ONCORHYNCHUS NERKA WALBAUM

1967 ◽  
Vol 45 (1) ◽  
pp. 117-126 ◽  
Author(s):  
M. A. Hafeez ◽  
P. Ford
Keyword(s):  
Sockeye Salmon ◽  
Pineal Organ ◽  
Subcommissural Organ ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Supporting Cells ◽  
Dependent Behavior ◽  
Aldehyde Fuchsin ◽  
Pineal Nerve ◽  
The Brain

The morphohistology and some histochemical aspects of the pineal organ in the sockeye salmon were studied. The distal part of the organ lies in a pineal fossa in the cranial roof. Photosensory cells and two kinds of ependymal supporting cells are present throughout its epithelium, which is entirely devoid of either melanin or lipofuchsin. Besides sensory nerve fibers, efferent end-loops are present on the photosensory as well as the supporting cells. The dorsal pineal nerve tract probably contains both sensory and efferent fibers. The apocrine secretion of sensory as well as some supporting cells is probably associated with either the maintenance of a constant chemical composition of the cerebrospinal fluid or with supply of certain chemical substances to the brain tissue. The secretion in the pineal and the subcommissural organ consists of glycogen, mucopolysaccharides, mucoproteins, and aldehyde fuchsin positive granules.It is proposed that the pineal organ is photosensory as well as secretory and that its photosensitivity might be of some significance in the light-dependent behavior of this species in terms of intensity detection.

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