scholarly journals Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia–Reperfusion in Rats

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 681 ◽  
Author(s):  
Ivan B. Filippenkov ◽  
Vasily V. Stavchansky ◽  
Alina E. Denisova ◽  
Vadim V. Yuzhakov ◽  
Larisa E. Sevan’kaeva ◽  
...  
Keyword(s):  
Cerebral Ischaemia ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Artery Occlusion ◽  
Biologically Active ◽  
Protective Properties ◽  
Ischaemia Reperfusion ◽  
Expression Of Genes ◽  
The Brain ◽  
Transcriptome Level

Cerebral ischaemia is the most common cause of impaired brain function. Biologically active peptides represent potential drugs for reducing the damage that occurs after ischaemia. The synthetic melanocortin derivative, ACTH(4-7)PGP (Semax), has been used successfully in the treatment of patients with severe impairment of cerebral blood circulation. However, its molecular mechanisms of action within the brain are not yet fully understood. Previously, we used the transient middle cerebral artery occlusion (tMCAO) model to study the damaging effects of ischaemia–reperfusion on the brain transcriptome in rats. Here, using RNA-Seq analysis, we investigated the protective properties of the Semax peptide at the transcriptome level under tMCAO conditions. We have identified 394 differentially expressed genes (DEGs) (>1.5-fold change) in the brains of rats at 24 h after tMCAO treated with Semax relative to saline. Following tMCAO, we found that Semax suppressed the expression of genes related to inflammatory processes and activated the expression of genes related to neurotransmission. In contrast, ischaemia–reperfusion alone activated the expression of inflammation-related genes and suppressed the expression of neurotransmission-related genes. Therefore, the neuroprotective action of Semax may be associated with a compensation of mRNA expression patterns that are disrupted during ischaemia–reperfusion conditions.

scholarly journals MicroRNAs as Potential Biomarkers in Atherosclerosis

2019 ◽  
Vol 20 (22) ◽  
pp. 5547 ◽  
Author(s):  
Alexey Churov ◽  
Volha Summerhill ◽  
Andrey Grechko ◽  
Varvara Orekhova ◽  
Alexander Orekhov
Keyword(s):  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Inflammatory Cells ◽  
Cellular Protein ◽  
Cholesterol Homeostasis ◽  
Transcriptional Level ◽  
High Morbidity ◽  
Industrialized Countries ◽  
Rna Molecules ◽  
Expression Of Genes

Atherosclerosis is a complex multifactorial disease that, despite advances in lifestyle management and drug therapy, remains to be the major cause of high morbidity and mortality rates from cardiovascular diseases (CVDs) in industrialized countries. Therefore, there is a great need in reliable diagnostic/prognostic biomarkers and effective treatment alternatives to reduce its burden. It was established that microRNAs (miRNAs/miRs), a class of non-coding single-stranded RNA molecules, can regulate the expression of genes at the post-transcriptional level and, accordingly, coordinate the cellular protein expression. Thus, they are involved not only in cell-specific physiological functions but also in the cellular and molecular mechanisms of human pathologies, including atherosclerosis. MiRNAs may be significant in the dysregulation that affects endothelial integrity, the function of vascular smooth muscle and inflammatory cells, and cellular cholesterol homeostasis that drives the initiation and growth of an atherosclerotic plaque. Besides, distinct expression patterns of several miRNAs are attributed to atherosclerotic and cardiovascular patients. In this article, the evidence indicating the multiple critical roles of miRNAs and their relevant molecular mechanisms related to atherosclerosis development and progression was reviewed. Moreover, the effects of miRNAs on atherosclerosis enabled to exploit them as novel diagnostic biomarkers and therapeutic targets that may lead to better management of atherosclerosis and CVDs.

scholarly journals Age effects aggressive behavior: RNA-seq analysis in cattle with implications for studying neoteny under domestication

2020 ◽  
Author(s):  
Paulina G. Eusebi ◽  
Natalia Sevane ◽  
Thomas O’Rourke ◽  
Manuel Pizarro ◽  
Cedric Boeckx ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Molecular Mechanisms ◽  
Rna Seq ◽  
Aggressive Behaviors ◽  
Intentional Actions ◽  
Expression Of Genes ◽  
Differential Gene ◽  
The Impact ◽  
The Brain ◽  
Novel Model

AbstractAggressiveness is one of the most basic behaviors, characterized by targeted intentional actions oriented to cause harm. The reactive type of aggression is regulated mostly by the brain’s prefrontal cortex; however, the molecular changes underlying aggressiveness in adults have not been fully characterized. Here we used an RNA-seq approach to investigate differential gene expression in the prefrontal cortex of bovines from the aggressive Lidia breed at different age stages: young three-year old and adult four-year-old bulls. A total of 50 up and 193 down-regulated genes in the adult group were identified. Furthermore, a cross-species comparative analysis retrieved 29 genes in common with previous studies on aggressive behaviors, representing an above-chance overlap with the differentially expressed genes in adult bulls.Particularly, we detected changes in the regulation of networks such as synaptogenesis, involved in maintenance and refinement of synapses, and the glutamate receptor pathway, which acts as excitatory driver in aggressive responses. Our results provide insights into candidate genes and networks involved in the molecular mechanisms leading to the maturation of the brain. The reduced reactive aggression typical of domestication has been proposed to form part of a retention of juvenile traits as adults (neoteny). The significant age-associated differential expression of genes implicated in aggressive behaviors and concomitant increase in Lidia cattle aggression validates this species as a novel model comparator to explore the impact of behavioral neoteny under domestication.

scholarly journals Brain and Pituitary Transcriptome Analyses Reveal the Differential Regulation of Reproduction-Related LncRNAs and mRNAs in Cynoglossus semilaevis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yani Dong ◽  
Likang Lyu ◽  
Haishen Wen ◽  
Bao Shi
Keyword(s):  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Interaction ◽  
Cynoglossus Semilaevis ◽  
Rna Seq ◽  
Tongue Sole ◽  
Gene Interaction Networks ◽  
Half Smooth Tongue Sole ◽  
The Brain

Long noncoding RNAs (lncRNAs) have been identified to be involved in half-smooth tongue sole (Cynoglossus semilaevis) reproduction. However, studies of their roles in reproduction have focused mainly on the ovary, and their expression patterns and potential roles in the brain and pituitary are unclear. Thus, to explore the mRNAs and lncRNAs that are closely associated with reproduction in the brain and pituitary, we collected tongue sole brain and pituitary tissues at three stages for RNA sequencing (RNA-seq), the 5,135 and 5,630 differentially expressed (DE) mRNAs and 378 and 532 DE lncRNAs were identified in the brain and pituitary, respectively. The RNA-seq results were verified by RT-qPCR. Moreover, enrichment analyses were performed to analyze the functions of DE mRNAs and lncRNAs. Interestingly, their involvement in pathways related to metabolism, signal transduction and endocrine signaling was revealed. LncRNA-target gene interaction networks were constructed based on antisense, cis and trans regulatory mechanisms. Moreover, we constructed competing endogenous RNA (ceRNA) networks. In summary, this study provides mRNA and lncRNA expression profiles in the brain and pituitary to understand the molecular mechanisms regulating tongue sole reproduction.

scholarly journals Natural Food Supplements Reduce Oxidative Stress in Primary Neurons and in the Mouse Brain, Suggesting Applications in the Prevention of Neurodegenerative Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 46
Author(s):  
Miriam Bobadilla ◽  
Josune García-Sanmartín ◽  
Alfredo Martínez
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Developed Countries ◽  
Food Supplements ◽  
Natural Food ◽  
Major Health Problem ◽  
Protective Properties ◽  
Expression Of Genes ◽  
The Brain

Neurodegenerative diseases pose a major health problem for developed countries, and stress has been identified as one of the main risk factors in the development of these disorders. Here, we have examined the protective properties against oxidative stress of several bioactive natural food supplements. We found that MecobalActive®, Olews®, and red and white grape seed polyphenol extracts may have a neuroprotective effect in vitro, both in the SH-SY 5Y cell line and in hippocampal neuron cultures, mainly by reducing reactive oxygen species levels and decreasing caspase-3 activity. In vivo, we demonstrated that oral administration of the supplements reduces the expression of genes involved in inflammation and oxidation mechanisms, whereas it increments the expression of genes related to protection against oxidative stress. Furthermore, we found that preventive treatment with these natural extracts increases the activity of antioxidant enzymes and prevents lipid peroxidation in the brain of stressed mice. Thus, our results indicate that some natural bioactive supplements may have important protective properties against oxidative stress processes occurring in the brain.

scholarly journals Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4–7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia–Reperfusion

2021 ◽  
Vol 22 (12) ◽  
pp. 6179
Author(s):  
Olga Yu. Sudarkina ◽  
Ivan B. Filippenkov ◽  
Vasily V. Stavchansky ◽  
Alina E. Denisova ◽  
Vadim V. Yuzhakov ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Subcortical Structures ◽  
Protein Levels ◽  
Expression Of Genes ◽  
A Genome ◽  
Neurotransmitter Genes

The Semax (Met-Glu-His-Phe-Pro-Gly-Pro) peptide is a synthetic melanocortin derivative that is used in the treatment of ischemic stroke. Previously, studies of the molecular mechanisms underlying the actions of Semax using models of cerebral ischemia in rats showed that the peptide enhanced the transcription of neurotrophins and their receptors and modulated the expression of genes involved in the immune response. A genome-wide RNA-Seq analysis revealed that, in the rat transient middle cerebral artery occlusion (tMCAO) model, Semax suppressed the expression of inflammatory genes and activated the expression of neurotransmitter genes. Here, we aimed to evaluate the effect of Semax in this model via the brain expression profiling of key proteins involved in inflammation and cell death processes (MMP-9, c-Fos, and JNK), as well as neuroprotection and recovery (CREB) in stroke. At 24 h after tMCAO, we observed the upregulation of active CREB in subcortical structures, including the focus of the ischemic damage; downregulation of MMP-9 and c-Fos in the adjacent frontoparietal cortex; and downregulation of active JNK in both tissues under the action of Semax. Moreover, a regulatory network was constructed. In conclusion, the suppression of inflammatory and cell death processes and the activation of recovery may contribute to the neuroprotective action of Semax at both the transcriptome and protein levels.

scholarly journals Differential regulation of the immune system in a brain-liver-fats organ network during short term fasting

2020 ◽  
Author(s):  
Susie S.Y. Huang ◽  
Melanie Makhlouf ◽  
Eman H. AbouMoussa ◽  
Mayra L. Ruiz Tejada Segura ◽  
Lisa S. Mathew ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Immune System ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Fine Tuning ◽  
Short Term ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Wide Range ◽  
The Brain

ABSTRACTDifferent fasting regimens are known to promote health, mitigate chronic immunological disorders, and improve age-related pathophysiological parameters in animals and humans. Indeed, several clinical trials are currently ongoing using fasting as a potential therapy for a wide range of conditions. Fasting alters metabolism by acting as a reset for energy homeostasis. However, the molecular mechanisms underlying the beneficial effects of short-term fasting (STF) are still not well understood, particularly at the systems or multi-organ level. Here, we investigated the dynamic gene expression patterns associated with six periods of STF in nine different mouse organs. We cataloged the transcriptional dynamics within and between organs during STF and discovered differential temporal effects of STF among organs. Using gene ontology enrichment analysis, we identified an organ network sharing 37 common biological pathways perturbed by STF. This network incorporates the brain, liver, interscapular brown adipose tissue, and posterior-subcutaneous white adipose tissue, hence we named it the brain-liver-fats organ network. Using Reactome pathways analysis, we identified the immune system, dominated by T cell regulation processes, as a central and prominent target of systemic modulations during STF in this organ network. The changes we identified in specific immune components point to the priming of adaptive immunity and parallel the fine-tuning of innate immune signaling. Our study provides a comprehensive multi-organ transcriptomic profiling of mice subjected to multiple periods of STF, and adds new insights into the molecular modulators involved in the systemic immuno-transcriptomic changes that occur during short-term energy loss.

scholarly journals Electroacupuncture Ameliorates Cognitive Impairment through Inhibition of Ca2+-Mediated Neurotoxicity in a Rat Model of Cerebral Ischaemia–reperfusion Injury

2018 ◽  
Vol 36 (6) ◽  
pp. 401-407 ◽  
Author(s):  
Yun Zhang ◽  
Xiang Mao ◽  
Ruhui Lin ◽  
Zuanfang Li ◽  
Jing Lin
Keyword(s):  
Cognitive Impairment ◽  
Rat Model ◽  
Cerebral Ischaemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Sprague Dawley ◽  
Ischaemia Reperfusion Injury ◽  
Tetrazolium Chloride ◽  
Ischaemia Reperfusion ◽  
Intracellular Ca

Background The hippocampus is vulnerable to severe damage after cerebral ischaemia–reperfusion (I/R) injury. This study aimed to explore the effect of electroacupuncture (EA) on cognitive impairment and its relationship with Ca2+neurotoxicity in a rat model of I/R injury induced by middle cerebral artery occlusion (MCAO). Methods 60 adult male Sprague-Dawley rats were randomly divided into three groups: control (sham surgery) group, untreated MCAO group and EA-treated MCAO+EA group. Rats in the MCAO and MCAO+EA groups underwent modelling of poststroke cognitive impairment by MCAO surgery. EA was performed for 30 min daily at GV20 and GV24 (1–20 Hz) for 1 week. The Morris water maze experiment was used to assess cognitive function. 2,3,5-triphenyl tetrazolium chloride staining was used to measure infarct volume. The intracellular Ca2+content in the Cornu Ammonis (CA)1 area of the hippocampus was assessed by laser confocal scanning microscopy. ELISA was performed to evaluate the concentration of glutamate (Glu) in the hippocampus, and the protein expression of two Glu receptors (N-methyl-D-aspartic acid receptor (NMDAR) 2A and NMDAR2B) were analysed by Western blotting. Results Compared with the untreated MCAO group, EA effectively ameliorated cognitive impairment (P=0.01) and shrunk the infarct volume (P=0.032). The content of intracellular Ca2+, Glu and NMDAR2B in the hippocampus was significantly raised by MCAO (P=0.031-0.043), while EA abrogated these effects. NMDAR2A was decreased by MCAO (P=0.015) but increased by EA (P=0.033). Conclusions EA had a beneficial effect on cognitive repair after cerebral I/R, and its mechanism of action likely involves a reduction of Ca2+influx via inhibition of Glu neurotoxicity and downregulation of NMDAR2B expression.

scholarly journals A Sphingosine 1-Phosphate Gradient Is Linked to the Cerebral Recruitment of T Helper and Regulatory T Helper Cells during Acute Ischemic Stroke

2020 ◽  
Vol 21 (17) ◽  
pp. 6242
Author(s):  
Alexandra Lucaciu ◽  
Hannah Kuhn ◽  
Sandra Trautmann ◽  
Nerea Ferreirós ◽  
Helmuth Steinmetz ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Expression Patterns ◽  
Treg Cells ◽  
Artery Occlusion ◽  
T Helper ◽  
Sphingosine 1 Phosphate ◽  
Cerebral Artery Occlusion ◽  
Kinetics Of ◽  
The Brain

Emerging evidence suggests a complex relationship between sphingosine 1-phosphate (S1P) signaling and stroke. Here, we show the kinetics of S1P in the acute phase of ischemic stroke and highlight accompanying changes in immune cells and S1P receptors (S1PR). Using a C57BL/6 mouse model of middle cerebral artery occlusion (MCAO), we assessed S1P concentrations in the brain, plasma, and spleen. We found a steep S1P gradient from the spleen towards the brain. Results obtained by qPCR suggested that cells expressing the S1PR type 1 (S1P1+) were the predominant population deserting the spleen. Here, we report the cerebral recruitment of T helper (TH) and regulatory T (TREG) cells to the ipsilateral hemisphere, which was associated with differential regulation of cerebral S1PR expression patterns in the brain after MCAO. This study provides insight that the S1P-S1PR axis facilitates splenic T cell egress and is linked to the cerebral recruitment of S1PR+ TH and TREG cells. Further insights by which means the S1P-S1PR-axis orchestrates neuronal positioning may offer new therapeutic perspectives after ischemic stroke.

scholarly journals Molecular basis of parental contributions to the behavioural tolerance of elevated pCO 2 in a coral reef fish

2021 ◽  
Vol 288 (1964) ◽  
Author(s):  
Alison A. Monroe ◽  
Celia Schunter ◽  
Megan J. Welch ◽  
Philip L. Munday ◽  
Timothy Ravasi
Keyword(s):  
Neural Plasticity ◽  
Parental Influence ◽  
Expression Patterns ◽  
Cellular Mechanisms ◽  
Maternal Line ◽  
Expression Of Genes ◽  
Behavioural Tolerance ◽  
Parental Phenotype ◽  
Neuron Growth ◽  
The Brain

Knowledge of adaptive potential is crucial to predicting the impacts of ocean acidification (OA) on marine organisms. In the spiny damselfish, Acanthochromis polyacanthus , individual variation in behavioural tolerance to elevated pCO 2 has been observed and is associated with offspring gene expression patterns in the brain. However, the maternal and paternal contributions of this variation are unknown. To investigate parental influence of behavioural pCO 2 tolerance, we crossed pCO 2 -tolerant fathers with pCO 2 -sensitive mothers and vice versa, reared their offspring at control and elevated pCO 2 levels, and compared the juveniles' brain transcriptional programme. We identified a large influence of parental phenotype on expression patterns of offspring, irrespective of environmental conditions. Circadian rhythm genes, associated with a tolerant parental phenotype, were uniquely expressed in tolerant mother offspring, while tolerant fathers had a greater role in expression of genes associated with histone binding. Expression changes in genes associated with neural plasticity were identified in both offspring types: the maternal line had a greater effect on genes related to neuron growth while paternal influence impacted the expression of synaptic development genes. Our results confirm cellular mechanisms involved in responses to varying lengths of OA exposure, while highlighting the parental phenotype's influence on offspring molecular phenotype.

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