scholarly journals Glucocorticoid-Dependent Mechanisms of Brain Tolerance to Hypoxia

2021 ◽  
Vol 22 (15) ◽  
pp. 7982
Author(s):  
Elena Rybnikova ◽  
Natalia Nalivaeva
Keyword(s):  
Cross Talk ◽  
Glucocorticoid Receptors ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Later Life ◽  
Adaptation To Hypoxia ◽  
Hypoxic Injury ◽  
Hypoxic Tolerance ◽  
Resistance To Stress ◽  
The Brain

Adaptation of organisms to stressors is coordinated by the hypothalamic-pituitary-adrenal axis (HPA), which involves glucocorticoids (GCs) and glucocorticoid receptors (GRs). Although the effects of GCs are well characterized, their impact on brain adaptation to hypoxia/ischemia is still understudied. The brain is not only the most susceptible to hypoxic injury, but also vulnerable to GC-induced damage, which makes studying the mechanisms of brain hypoxic tolerance and resistance to stress-related elevation of GCs of great importance. Cross-talk between the molecular mechanisms activated in neuronal cells by hypoxia and GCs provides a platform for developing the most effective and safe means for prevention and treatment of hypoxia-induced brain damage, including hypoxic pre- and post-conditioning. Taking into account that hypoxia- and GC-induced reprogramming significantly affects the development of organisms during embryogenesis, studies of the effects of prenatal and neonatal hypoxia on health in later life are of particular interest. This mini review discusses the accumulated data on the dynamics of the HPA activation in injurious and non-injurious hypoxia, the role of the brain GRs in these processes, interaction of GCs and hypoxia-inducible factor HIF-1, as well as cross-talk between GC and hypoxic signaling. It also identifies underdeveloped areas and suggests directions for further prospective studies.

scholarly journals Evolutionary conserved neural signature of early life stress affects animal social competence

2018 ◽  
Vol 285 (1871) ◽  
pp. 20172344 ◽  
Author(s):  
Cecilia Nyman ◽  
Stefan Fischer ◽  
Nadia Aubin-Horth ◽  
Barbara Taborsky
Keyword(s):  
Social Competence ◽  
Social Environment ◽  
Life Stress ◽  
Glucocorticoid Receptors ◽  
Molecular Mechanisms ◽  
Cichlid Fish ◽  
Early Life Stress ◽  
Later Life ◽  
Stress Axis ◽  
Molecular Pathway

In vertebrates, the early social environment can persistently influence behaviour and social competence later in life. However, the molecular mechanisms underlying variation in animal social competence are largely unknown. In rats, high-quality maternal care causes an upregulation of hippocampal glucocorticoid receptors ( gr ) and reduces offspring stress responsiveness. This identifies gr regulation as a candidate mechanism for maintaining variation in animal social competence. We tested this hypothesis in a highly social cichlid fish, Neolamprologus pulcher , reared with or without caring parents. We find that the molecular pathway translating early social experience into later-life alterations of the stress axis is homologous across vertebrates: fish reared with parents expressed the glucocorticoid receptor gr1 more in the telencephalon. Furthermore, expression levels of the transcription factor egr-1 (early growth response 1) were associated with gr1 expression in the telencephalon and hypothalamus. When blocking glucocorticoid receptors (GR) with an antagonist, mifepristone (RU486), parent-reared individuals showed more socially appropriate, submissive behaviour when intruding on a larger conspecific's territory. Remarkably, mifepristone-treated fish were less attacked by territory owners and had a higher likelihood of territory takeover. Our results indicate that early social-environment effects on stress axis programming are mediated by an evolutionary conserved molecular pathway, which is causally involved in environmentally induced variation of animal social competence.

scholarly journals Hypoxic regulation of erythropoiesis and iron metabolism

2010 ◽  
Vol 299 (1) ◽  
pp. F1-F13 ◽  
Author(s):  
Volker H. Haase
Keyword(s):  
Transcription Factor ◽  
Blood Cell ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Oxygen Sensor ◽  
Hypoxia Inducible Factor ◽  
Adaptation To Hypoxia ◽  
Cellular Adaptation ◽  
Hypoxic Induction ◽  
Highly Sensitive

The kidney is a highly sensitive oxygen sensor and plays a central role in mediating the hypoxic induction of red blood cell production. Efforts to understand the molecular basis of oxygen-regulated erythropoiesis have led to the identification of erythropoietin (EPO), which is essential for normal erythropoiesis and to the purification of hypoxia-inducible factor (HIF), the transcription factor that regulates EPO synthesis and mediates cellular adaptation to hypoxia. Recent insights into the molecular mechanisms that control and integrate cellular and systemic erythropoiesis-promoting hypoxia responses and their potential as a therapeutic target for the treatment of renal anemia are discussed in this review.

scholarly journals Regulation of HIF-1α and p53 in stress responses in the subterranean rodents Lasiopodomys mandarinus and Lasiopodomys brandtii (Rodentia: Cricetidae)

2021 ◽  
Vol 38 ◽  
pp. 1-11
Author(s):  
Luye Shi ◽  
Mengwan Jiang ◽  
Mengyang Li ◽  
Xiaozhen Shang ◽  
Xiujuan Li ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Stress Responses ◽  
Adaptation To Hypoxia ◽  
Subterranean Rodents ◽  
Interaction Patterns ◽  
P53 Expression ◽  
Hippocampal Ca1 ◽  
Hypoxic Tolerance ◽  
The Brain ◽  
Lasiopodomys Brandtii

The response mechanism and interaction patterns of HIF-1α and p53 in animals in an hypoxic environment are crucial for their hypoxic tolerance and adaptation. Many studies have shown that underground rodents have better hypoxic adaptation characteristics. However, the mechanism by which HIF-1α and p53 in underground rodents respond to hypoxic environments compared with in ground rodents remains unclear. Further, whether a synergy between HIF-1α and p53 enables animals tolerate extremely hypoxic environments is unclear. We studied HIF-1α and p53 expression in the brain tissue and cell apoptosis in the hippocampal CA1 region during 6 hours of acute hypoxia (5% oxygen) in Lasiopodomys mandarinus (Milne-Edwards, 1871) and Lasiopodomys brandtii (Radde, 1861), two closely related small rodents with different life characteristics (underground and aboveground, respectively), using a comparative biology method to determine the mechanisms underlying their adaptation to this environment. Our results indicate that HIF-1α and p53 expression is more rapid in L. mandarinus than in L. brandtii under acute hypoxic environments, resulting in a significant synergistic effect in L. mandarinus. Correlation analysis revealed that HIF-1α expression and the apoptotic index of the hippocampal CA1 regions of the brain tissues of L. mandarinus and L. brandtii, both under hypoxia, were significantly negatively and positively correlated, respectively. Long-term existence in underground burrow systems could enable better adaptation to hypoxia in L. mandarinus than in L. brandtii. We speculate that L. mandarinus can quickly eliminate resulting damage via the synergistic effect of p53 and HIF-1α in response to acute hypoxic environments, helping the organism quickly return to a normal state after the stress.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain’s pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain’s disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

scholarly journals Sublethal Exposure Effects of the Neonicotinoid Clothianidin Strongly Modify the Brain Transcriptome and Proteome in the Male Moth Agrotis ipsilon

Insects ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 152
Author(s):  
Camille Meslin ◽  
Françoise Bozzolan ◽  
Virginie Braman ◽  
Solenne Chardonnet ◽  
Cédric Pionneau ◽  
...  
Keyword(s):  
Sex Pheromone ◽  
Molecular Mechanisms ◽  
Insect Pest ◽  
Agrotis Ipsilon ◽  
Positive Effects ◽  
Male Moth ◽  
Hormetic Effect ◽  
Pest Insects ◽  
Neuronal Processes ◽  
The Brain

Insect pest management relies mainly on neurotoxic insecticides, including neonicotinoids such as clothianidin. The residual accumulation of low concentrations of these insecticides can have positive effects on target pest insects by enhancing various life traits. Because pest insects often rely on sex pheromones for reproduction and olfactory synaptic transmission is cholinergic, neonicotinoid residues could indeed modify chemical communication. We recently showed that treatments with low doses of clothianidin could induce hormetic effects on behavioral and neuronal sex pheromone responses in the male moth, Agrotis ipsilon. In this study, we used high-throughput RNAseq and proteomic analyses from brains of A. ipsilon males that were intoxicated with a low dose of clothianidin to investigate the molecular mechanisms leading to the observed hormetic effect. Our results showed that clothianidin induced significant changes in transcript levels and protein quantity in the brain of treated moths: 1229 genes and 49 proteins were differentially expressed upon clothianidin exposure. In particular, our analyses highlighted a regulation in numerous enzymes as a possible detoxification response to the insecticide and also numerous changes in neuronal processes, which could act as a form of acclimatization to the insecticide-contaminated environment, both leading to enhanced neuronal and behavioral responses to sex pheromone.

scholarly journals DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
The Past ◽  
Targeted Analysis ◽  
Lack Of Information ◽  
High Resolution Power ◽  
Resolution Level ◽  
Health And Disease ◽  
High Doses ◽  
The Brain

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.

scholarly journals Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1715
Author(s):  
Macus Hao-Ran Bao ◽  
Carmen Chak-Lui Wong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Liver Cancer ◽  
Effective Treatment ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Metabolic Reprogramming ◽  
Combination Therapies ◽  
Low Oxygen ◽  
Treatment Regimens

Hypoxia, low oxygen (O2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.

scholarly journals Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Virginia Egea ◽  
Kai Kessenbrock ◽  
Devon Lawson ◽  
Alexander Bartelt ◽  
Christian Weber ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Human Mesenchymal Stem Cells ◽  
Target Cells ◽  
Autophagic Flux ◽  
Stromal Cell Derived Factor

AbstractBone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.

Sign in / Sign up

Export Citation Format

Share Document