MicroRNA Biomarkers in Traumatic Brain Injury

Neurotrauma ◽  
2018 ◽  
pp. 261-268
Author(s):  
Manish Bhomia ◽  
Nagaraja S. Balakathiresan ◽  
Kevin K. W. Wang ◽  
Barbara Knollmann-Ritschel
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Critical Role ◽  
Regulate Gene Expression ◽  
Rna Molecules ◽  
Posttranscriptional Level ◽  
Potential Use ◽  
Regulate Gene

Traumatic brain injury (TBI) is currently considered one of the major causes of disability and death worldwide. The cellular and molecular changes of TBI pathology are dynamic and complex in nature. MicroRNAs (miRNA) are small endogenous RNA molecules that regulate gene expression at the posttranscriptional level. Several studies have shown a critical role of miRNAs in the development of long- and short-term TBI pathology. Circulating miRNAs are of great interest as blood-based biomarkers in TBI diagnosis. In this chapter, the authors review recent reports that aim to understand the role of miRNAs in TBI pathophysiology and their potential use as a therapeutic target. Additionally, the authors discuss the potential use of miRNAs as blood-based diagnostic markers for TBI and their possible association with other neurodegenerative diseases.

Updates on the Current Technologies for microRNA Profiling

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Rebecca Mathew ◽  
Valentina Mattei ◽  
Muna Al Hashmi ◽  
Sara Tomei
Keyword(s):  
Gene Expression ◽  
Special Focus ◽  
Healthy Individuals ◽  
Regulate Gene Expression ◽  
Rna Molecules ◽  
Cellular Processes ◽  
Microrna Profiling ◽  
Regulate Gene

MicroRNAs are RNA molecules of ~22 nt length that regulate gene expression posttranscriptionally. The role of miRNAs has been reported in many cellular processes including apoptosis, cell differentiation, development and proliferation. The dysregulated expression of miRNAs has been proposed as a biomarker for the diagnosis, onset and prognosis of human diseases. The utility of miRNA profiles to identify and discriminate patients from healthy individuals is highly dependent on the sensitivity and specificity of the technologies used for their detection and the quantity and quality of starting material. In this review, we present an update of the current technologies for the extraction, QC assessment and detection of miRNAs with special focus to the most recent methods, discussing their advantages as well as their shortcomings.

scholarly journals Regulation of Phosphorylated State of NMDA Receptor by STEP61 Phosphatase after Mild-Traumatic Brain Injury: Role of Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1575
Author(s):  
Francisco J. Carvajal ◽  
Waldo Cerpa
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Tyrosine Phosphatase ◽  
Critical Role ◽  
Synaptic Function ◽  
Fyn Kinase ◽  
Impact Device ◽  
Traumatic Lesions ◽  
Early Biomarker

Traumatic Brain Injury (TBI) mediates neuronal death through several events involving many molecular pathways, including the glutamate-mediated excitotoxicity for excessive stimulation of N-methyl-D-aspartate receptors (NMDARs), producing activation of death signaling pathways. However, the contribution of NMDARs (distribution and signaling-associated to the distribution) remains incompletely understood. We propose a critical role of STEP61 (Striatal-Enriched protein tyrosine phosphatase) in TBI; this phosphatase regulates the dephosphorylated state of the GluN2B subunit through two pathways: by direct dephosphorylation of tyrosine-1472 and indirectly via dephosphorylation and inactivation of Fyn kinase. We previously demonstrated oxidative stress’s contribution to NMDAR signaling and distribution using SOD2+/− mice such a model. We performed TBI protocol using a controlled frontal impact device using C57BL/6 mice and SOD2+/− animals. After TBI, we found alterations in cognitive performance, NMDAR-dependent synaptic function (decreased synaptic form of NMDARs and decreased synaptic current NMDAR-dependent), and increased STEP61 activity. These changes are reduced partially with the STEP61-inhibitor TC-2153 treatment in mice subjected to TBI protocol. This study contributes with evidence about the role of STEP61 in the neuropathological progression after TBI and also the alteration in their activity, such as an early biomarker of synaptic damage in traumatic lesions.

scholarly journals miR-29a-5p Alleviates Traumatic Brain Injury (TBI)-Induced Permeability Disruption Via Regulating NLRP3 Pathway

2021 ◽  
Author(s):  
Aijun Zhang ◽  
Youming Lu ◽  
Lei Yuan ◽  
Pengqi Zhang ◽  
Dongdong Zou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Endothelial Cell ◽  
Brain Injury ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Promising Strategy ◽  
Pathway Activation ◽  
Nlrp3 Expression

Abstract Blood-brain barrier (BBB) dysfunction is presented during traumatic brain injury (TBI) and is dependent upon the activation of the NLRP3/Caspase-1 inflammasome pathway. MicroRNA (miRNA) was proved to inhibit signaling pathway activation by targeting gene expression and we predicated in the database that miR-29a targets to NLRP3. Herein, this study aims to define the regulating role of miR-29a in NLRP3 expression and NLRP3/Caspase-1 inflammasome activation in TBI-induced BBB dysfunction. Our results indicated that miR-29a-5p alleviates TBI-induced the increased permeability of endothelial cell and BBB via suppressing NLRP3 expression and NLRP3/Caspase-1 inflammasome activation, providing a promising strategy for relieving TBI via inhibiting NLRP3/Caspase-1 inflammasome activation.

Biopsychosocial pathways to mental health and disease across the lifespan: The emerging role of epigenetics

2020 ◽  
pp. 190-206
Author(s):  
Charlotte A.M. Cecil
Keyword(s):  
Gene Expression ◽  
Mental Health ◽  
Dna Methylation ◽  
Mental Illness ◽  
Psychiatric Disorders ◽  
Regulate Gene Expression ◽  
Health And Disease ◽  
Regulate Gene ◽  
Epigenetic Processes

The biopsychosocial (BPS) model of psychiatry has had a major impact on our modern conceptualization of mental illness as a complex, multi-determined phenomenon. Yet, interdisciplinary BPS work remains the exception, rather than the rule in psychiatry. It has been suggested that this may stem in part from a failure of the BPS model to clearly delineate the mechanisms through which biological, psychological, and social factors co-act in the development of mental illness. This chapter discusses how epigenetic processes that regulate gene expression, such as DNA methylation, are fast emerging as a candidate mechanism for BPS interactions, with potentially widespread implications for the way that psychiatric disorders are understood, assessed, and, perhaps in future, even treated.

scholarly journals Polyamines regulate gene expression by stimulating translation of histone acetyltransferase mRNAs

2020 ◽  
Vol 295 (26) ◽  
pp. 8736-8745 ◽  
Author(s):  
Akihiko Sakamoto ◽  
Yusuke Terui ◽  
Takeshi Uemura ◽  
Kazuei Igarashi ◽  
Keiko Kashiwagi
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Histone Acetyltransferases ◽  
Regulate Gene Expression ◽  
Double Stranded Rna ◽  
Protein Levels ◽  
Lysine Residues ◽  
Regulate Gene ◽  
Stimulation Of

Polyamines regulate gene expression in Escherichia coli by translationally stimulating mRNAs encoding global transcription factors. In this study, we focused on histone acetylation, one of the mechanisms of epigenetic regulation of gene expression, to attempt to clarify the role of polyamines in the regulation of gene expression in eukaryotes. We found that activities of histone acetyltransferases in both the nucleus and cytoplasm decreased significantly in polyamine-reduced mouse mammary carcinoma FM3A cells. Although protein levels of histones H3 and H4 did not change in control and polyamine-reduced cells, acetylation of histones H3 and H4 was greatly decreased in the polyamine-reduced cells. Next, we used control and polyamine-reduced cells to identify histone acetyltransferases whose synthesis is stimulated by polyamines. We found that polyamines stimulate the translation of histone acetyltransferases GCN5 and HAT1. Accordingly, GCN5- and HAT1-catalyzed acetylation of specific lysine residues on histones H3 and H4 was stimulated by polyamines. Consistent with these findings, transcription of genes required for cell proliferation was enhanced by polyamines. These results indicate that polyamines regulate gene expression by enhancing the expression of the histone acetyltransferases GCN5 and HAT1 at the level of translation. Mechanistically, polyamines enhanced the interaction of microRNA-7648-5p (miR-7648-5p) with the 5′-UTR of GCN5 mRNA, resulting in stimulation of translation due to the destabilization of the double-stranded RNA (dsRNA) between the 5′-UTR and the ORF of GCN5 mRNA. Because HAT1 mRNA has a short 5′-UTR, polyamines may enhance initiation complex formation directly on this mRNA.

Abscisic acid and stress regulate gene expression during germination of chick-pea seeds. Possible role of calcium

1994 ◽  
Vol 91 (3) ◽  
pp. 461-467 ◽  
Author(s):  
Pilar Colorado ◽  
Antonio Rodriguez ◽  
Gregorio Nicolas ◽  
Dolores Rodriguez
Keyword(s):  
Gene Expression ◽  
Abscisic Acid ◽  
Regulate Gene Expression ◽  
Chick Pea ◽  
Pea Seeds ◽  
Regulate Gene

scholarly journals MiR-147: Functions and Implications in Inflammation and Diseases

MicroRNA ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ling Lin ◽  
Kebin Hu
Keyword(s):  
Gene Expression ◽  
Infectious Disease ◽  
Neurodegenerative Disorder ◽  
Mrna Translation ◽  
Transcriptional Level ◽  
Regulate Gene Expression ◽  
Inflammatory Bowel ◽  
Non Coding Rnas ◽  
Regulate Gene

: MicroRNAs (miRNAs) are small non-coding RNAs (19~25 nucleotides) that regulate gene expression at a post-transcriptional level through repression of mRNA translation or mRNA decay. miR-147, which was initially discovered in mouse spleen and macrophages, has been shown to correlate with coronary atherogenesis and inflammatory bowel disease and modulate macrophage functions and inflammation through TLR-4. The altered miR-147 level has been shown in various human diseases, including infectious disease, cancer, cardiovascular disease, a neurodegenerative disorder, etc. This review will focus on the current understanding regarding the role of miR-147 in inflammation and diseases.

scholarly journals Obesity, Insulin Resistance, and Colorectal Cancer: Could miRNA Dysregulation Play a Role?

2019 ◽  
Vol 20 (12) ◽  
pp. 2922 ◽  
Author(s):  
Francesca Cirillo ◽  
Cecilia Catellani ◽  
Chiara Sartori ◽  
Pietro Lazzeroni ◽  
Sergio Amarri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Insulin Resistance ◽  
Low Grade ◽  
Regulate Gene Expression ◽  
New Perspective ◽  
Obesity And Cancer ◽  
Low Grade Inflammation ◽  
Regulate Gene

Obesity is associated with insulin resistance and low-grade inflammation. Insulin resistance is a risk factor for cancer. A recent chapter in epigenetics is represented by microRNAs (miRNAs), which post-transcriptionally regulate gene expression. Dysregulated miRNA profiles have been associated with diseases including obesity and cancer. Herein we report dysregulated miRNAs in obesity both in animal models and in humans, and we also document dysregulated miRNAs in colorectal cancer (CRC), as example of an obesity-related cancer. Some of the described miRNAs are found to be similarly dysregulated both in obesity, insulin resistance (IR), and CRC. Thus, we present miRNAs as a potential molecular link between obesity and CRC onset and development, giving a new perspective on the role of miRNAs in obesity-associated cancers.

scholarly journals Zinc and Traumatic Brain Injury: From Chelation to Supplementation

2020 ◽  
Vol 8 (3) ◽  
pp. 36 ◽  
Author(s):  
Cathy W. Levenson
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Incidence Rate ◽  
Molecular Mechanisms ◽  
Behavioral Deficits ◽  
Zinc Accumulation ◽  
Regulated Gene Expression

With a worldwide incidence rate of almost 70 million annually, traumatic brain injury (TBI) is a frequent cause of both disability and death. Our modern understanding of the zinc-regulated neurochemical, cellular, and molecular mechanisms associated with TBI is the result of a continuum of research spanning more than three decades. This review describes the evolution of the field beginning with the initial landmark work on the toxicity of excess neuronal zinc accumulation after injury. It further shows how the field has expanded and shifted to include examination of the cellular pools of zinc after TBI, identification of the role of zinc in TBI-regulated gene expression and neurogenesis, and the use of zinc to prevent cognitive and behavioral deficits associated with brain injury.

scholarly journals Histone exchange is associated with activator function at transcribed promoters and with repression at histone loci

2020 ◽  
Vol 6 (36) ◽  
pp. eabb0333
Author(s):  
Sari Kassem ◽  
Paolo Ferrari ◽  
Amanda L. Hughes ◽  
Julien Soudet ◽  
Oliver J. Rando ◽  
...  
Keyword(s):  
Gene Expression ◽  
Causal Relationship ◽  
Mode Of Action ◽  
Transcriptional Repression ◽  
Transcriptional Activity ◽  
Gene Promoters ◽  
Regulate Gene Expression ◽  
Histone Exchange ◽  
Regulate Gene

Transcription in eukaryotes correlates with major chromatin changes, including the replacement of old nucleosomal histones by new histones at the promoters of genes. The role of these histone exchange events in transcription remains unclear. In particular, the causal relationship between histone exchange and activator binding, preinitiation complex (PIC) assembly, and/or subsequent transcription remains unclear. Here, we provide evidence that histone exchange at gene promoters is not simply a consequence of PIC assembly or transcription but instead is mediated by activators. We further show that not all activators up-regulate gene expression by inducing histone turnover. Thus, histone exchange does not simply correlate with transcriptional activity, but instead reflects the mode of action of the activator. Last, we show that histone turnover is not only associated with activator function but also plays a role in transcriptional repression at the histone loci.

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