Abstract:
:Peroxisome proliferator activated receptors (PPARs) are nuclear hormone receptors that act as transcription factors in response to endogenous lipid messengers. The fibrates and thiazolidinediones are synthetic PPAR agonists used clinically to treat dyslipidemia and Type 2 Diabetes Mellitus, respectively, but also improve symptoms of several other diseases. Transposable elements (TEs), repetitive sequences in mammalian genomes, are implicated in many of the same conditions for which PPAR agonists are therapeutic, including neurodegeneration, schizophrenia, and drug addiction. We tested the hypothesis that there is a link between actions of PPAR agonists and TE expression. We developed an innovative application of microarray data by mapping Illumina mouse WG-6 microarray probes to areas of the mouse genome that contain TEs. Using this information, we assessed the effects of systemic administration of three PPAR agonists with different PPAR subtype selectivity: fenofibrate, tesaglitazar, and bezafibrate, on TE probe expression in mouse brain [prefrontal cortex (PFC) and amygdala] and liver. We found that fenofibrate, and bezafibrate to a lesser extent, up-regulated probes mapped to retrotransposons: Short-Interspersed Elements (SINEs) and Long-Interspersed Elements (LINEs), in the PFC. Conversely, all PPAR agonists down-regulated LINEs and tesaglitazar and bezafibrate also down-regulated SINEs in liver. We built gene coexpression networks that partitioned the diverse transcriptional response to PPAR agonists into groups of probes with highly correlated expression patterns (modules). Most of the differentially expressed retrotransposons were within the same module, suggesting coordinated regulation of their expression, possibly by PPAR signaling. One TE module was conserved across tissues and was enriched with genes whose products participate in epigenetic regulation, suggesting that PPAR agonists affect TE expression via epigenetic mechanisms. Other enriched functional categories included phenotypes related to embryonic development and learning and memory, suggesting functional links between these biological processes and TE expression. In summary, these findings suggest mechanistic relationships between retrotransposons and PPAR agonists and provide a basis for future exploration of their functional roles in brain and liver.
journal_name
Front Mol Neuroscijournal_title
Frontiers in molecular neuroscienceauthors
Ferguson LB,Zhang L,Wang S,Bridges C,Harris RA,Ponomarev Idoi
10.3389/fnmol.2018.00331subject
Has Abstractpub_date
2018-09-19 00:00:00pages
331issn
1662-5099journal_volume
11pub_type
杂志文章abstract::In the last decade, bioinformatic analyses of high-throughput proteomics and transcriptomics data have enabled researchers to gain insight into the molecular networks that may underlie lasting changes in synaptic efficacy. Development and utilization of these techniques have advanced the field of learning and memory s...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00045
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abstract::Neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA) are chronic, progressive, and age-associated neurological disorders characterized by neuronal deterioration in specific brain regions. Although the specific path...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2019.00141
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abstract::Glycine receptors (GlyRs) containing the α2 subunit are highly expressed in the developing brain, where they regulate neuronal migration and maturation, promote spontaneous network activity and subsequent development of synaptic connections. Mutations in GLRA2 are associated with autism spectrum disorder, but the unde...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00380
更新日期:2018-10-15 00:00:00
abstract::γ-Aminobutyric acid type A receptors (GABAARs) mediate the majority of fast synaptic inhibition in the central nervous system (CNS). GABAARs belong to the Cys-loop superfamily of pentameric ligand-gated ion channels (pLGIC) and are assembled from 19 different subunits. As dysfunctional GABAergic neurotransmission mani...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00191
更新日期:2019-08-07 00:00:00
abstract::There are many unanswered questions about the roles of the actin pointed end capping and actin nucleation by tropomodulins (Tmod) in regulating neural morphology. Previous studies indicate that Tmod1 and Tmod2 regulate morphology of the dendritic arbor and spines. Tmod3, which is expressed in the brain, had only a min...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00357
更新日期:2018-10-09 00:00:00
abstract::Spinal cord injury (SCI) causes the death of neurons and glial cells due to the initial mechanical forces (i.e., primary injury) and through a cascade of secondary molecular events (e.g., inflammation or excitotoxicity) that exacerbate cell death. The loss of neurons and glial cells that are not replaced after the inj...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2018.00101
更新日期:2018-04-03 00:00:00
abstract::Spinal cord injury (SCI) can result in an irreversible disability due to loss of sensorimotor function below the lesion. Presently, clinical treatments for SCI mainly include surgery, drugs and postoperative rehabilitation. The prospective roles of bioscaffolds and exosomes in several neurological diseases have been r...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00081
更新日期:2019-04-12 00:00:00
abstract::Alzheimer's disease (AD) is a progressive disease with early degeneration of the central cholinergic neurons. Currently, three of four AD drugs act by inhibiting the acetylcholine (ACh) degrading enzyme, acetylcholinesterase (AChE). Efficacy of these drugs depends on available amount of ACh, which is biosynthesized by...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00239
更新日期:2019-10-11 00:00:00
abstract::Neuronal identity is generated by the cell-surface expression of clustered protocadherin (Pcdh) isoforms. In mice, 58 isoforms from three gene clusters, Pcdhα, Pcdhβ, and Pcdhγ, are differentially expressed in neurons. Since cis-heteromeric Pcdh oligomers on the cell surface interact homophilically with that in other ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00114
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abstract::Genetic studies have managed to explain many cases of familial amyotrophic lateral sclerosis (ALS) through mutations in several genes. However, the cause of a majority of sporadic cases remains unknown. Recently, epigenetics, especially miRNA studies, show some promising aspects. We aimed to evaluate the differential ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00106
更新日期:2018-04-04 00:00:00
abstract::Parkinson's disease (PD) is a progressive CNS disorder that is primarily associated with impaired movement. PD develops over decades and is linked to the gradual loss of dopamine delivery to the striatum, via the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). While the administration o...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00010
更新日期:2019-02-11 00:00:00
abstract::Mercury is a toxic metal that can be found in the environment in three different forms - elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood-brain barrier. For this reason, exposure models that use inorganic ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00125
更新日期:2018-05-15 00:00:00
abstract::Studies on the association between post-traumatic stress disorder (PTSD) and levels of catecholamines have yielded inconsistent results. The aim of this study was to conduct a systematic review and meta-analysis to assess whether concentrations of the catecholamines dopamine, norepinephrine, and epinephrine are associ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00450
更新日期:2018-12-04 00:00:00
abstract::The importance of catecholamines in post-traumatic stress disorder (PTSD) still needs to be explored. We aimed to evaluate epinephrine's (EPI) causal role and molecular mechanism for the persistence of PTSD traumatic memories. Wild-type (WT) and EPI-deficient mice (phenylethanolamine-N-methyltransferase-knockout mice,...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.588802
更新日期:2020-10-26 00:00:00
abstract::Maternal cigarette smoke exposure (SE) causes detrimental changes associated with the development of chronic neurological diseases in the offspring as a result of oxidative mitochondrial damage. Maternal L-Carnitine administration has been shown to reduce renal oxidative stress in SE offspring, but its effect in the b...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00033
更新日期:2017-02-13 00:00:00
abstract::Sex-determining region Y box 2 (Sox2), expressed in neural tissues, plays an important role as a transcription factor not only in the pluripotency and proliferation of neuronal cells but also in the opposite function of cell differentiation. Nevertheless, how Sox2 is linked to motor neuron development remains unknown....
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00034
更新日期:2020-03-27 00:00:00
abstract::Emerging studies have demonstrated that interleukin (IL)-33 and its receptor ST2 act as key factors in inflammatory diseases. Moreover, accumulating evidence has suggested that cytokines, including tumor necrosis factor (TNF)-α and IL-1β, trigger an inflammatory cascade. SIRT1 has been shown to suppress the expression...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00017
更新日期:2020-02-12 00:00:00
abstract::The cells of the neural crest, often referred to as neural crest stem cells, give rise to a number of sub-lineages, one of which is Schwann cells, the glial cells of peripheral nerves. Crest cells transform to adult Schwann cells through the generation of two well defined intermediate stages, the Schwann cell precurso...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2019.00069
更新日期:2019-03-26 00:00:00
abstract::Hoxa5 is a member of the Hox gene family that plays critical roles in successive steps of the central nervous system formation during embryonic and fetal development. In the mouse, Hoxa5 was recently shown to be expressed in the medulla oblongata and the pons from fetal stages to adulthood. In these territories, Hoxa5...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00369
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abstract::Thiol groups can undergo numerous modifications, making cysteine a unique molecular switch. Cysteine plays structural and regulatory roles as part of proteins or glutathione, contributing to maintain redox homeostasis and regulate signaling within and amongst cells. Not surprisingly therefore, cysteines are associated...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00167
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abstract::Atypical Parkinson syndromes (APSs) often have symptoms that overlap with those of Parkinson's disease (PD), especially early in the disease, making these disorders difficult to diagnose. Previous studies have demonstrated an association of oligomeric α-synuclein (α-Syn), a key element in the pathogenesis of PD, with ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00129
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abstract::Being the most common cause of dementia, AD is a polygenic and neurodegenerative disease. Complex and multiple factors have been shown to be involved in its pathogenesis, of which the genetics play an indispensable role. It is widely accepted that discovery of potential genes related to the pathogenesis of AD would be...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00319
更新日期:2017-10-06 00:00:00
abstract::Rod and cone phosphodiesterase 6 (PDE6) are key effector enzymes of the vertebrate phototransduction pathway. Rod PDE6 consists of two catalytic subunits PDE6α and PDE6β and two identical inhibitory PDE6γ subunits, while cone PDE6 is composed of two identical PDE6α' catalytic subunits and two identical cone-specific P...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00233
更新日期:2018-07-09 00:00:00
abstract::It is widely accepted that glutamate is the most important excitatory neurotransmitter in the central nervous system (CNS). However, there is also a large amount of glutamate in the blood. Generally, the concentration gradient of glutamate between intraparenchymal and blood environments is stable. However, this gradie...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00400
更新日期:2017-12-05 00:00:00
abstract::Long non-coding RNAs (lncRNAs) have emerged as an important regulatory control in biological systems. Though the field of lncRNA has been progressing rapidly, a complete understanding of the role of lncRNAs in neuroblastoma pathogenesis is still lacking. To identify the abrogated lncRNAs in primary neuroblastoma and i...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00293
更新日期:2019-12-12 00:00:00
abstract::Background: An imbalance between total training load and total recovery may cause overtraining (OT). The purpose of the present study was to verify the effects of OT on the expression of brain-derived neurotrophic factor (BDNF), its receptor tropomyosin receptor kinase B (TrkB) and p75 and the dynamic expression patte...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00007
更新日期:2020-01-30 00:00:00
abstract::Connexin channels play numerous essential roles in virtually every organ by mediating solute exchange between adjacent cells, or between cytoplasm and extracellular milieu. Our understanding of the structure-function relationship of connexin channels relies on X-ray crystallographic data for human connexin 26 (hCx26) ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00170
更新日期:2018-05-31 00:00:00
abstract::The brain contains an enormous, but finite, number of neurons. The ability of this limited number of neurons to produce nearly limitless neural information over a lifetime is typically explained by combinatorial explosion; that is, by the exponential amplification of each neuron's contribution through its incorporatio...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2012.00045
更新日期:2012-04-12 00:00:00
abstract::Aim: Traumatic brain injury (TBI) is a leading cause of mortality/morbidity and is associated with chronic neuroinflammation. Melanocortin receptor agonists including adrenocorticotropic hormone (ACTH) ameliorate inflammation and provide a novel therapeutic approach. We examined the effect of long-acting cosyntropin (...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00109
更新日期:2020-06-26 00:00:00
abstract::Kainate (KA) is a potent neurotoxin that has been widely used experimentally to induce acute brain seizures and, after repetitive treatments, as a chronic model of temporal lobe epilepsy (TLE), with similar features to those observed in human patients with TLE. However, whether KA activates KA receptors (KARs) as an a...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2018.00217
更新日期:2018-06-22 00:00:00