Expression and distribution of neuroglobin and hypoxia-inducible factor-1α in the diencephalon of young yaks

The diencephalon, or interbrain, is a primary relay and processing center for sensory information and autonomic control. It connects structures of the endocrine system with the nervous system and works with the limbic system to generate and manage emotions and memories. Neuroglobin (Ngb) is a member of the vertebrate globin family involved in cellular oxygen homeostasis and reactive oxygen/nitrogen scavenging, while hypoxia-inducible factor (Hif-1α) is a transcription factors that respond to decreases in available oxygen in the cellular environment or hypoxia. The study explored the expression of Ngb and Hif-1α in the diencephalon of young yaks and examined factors that influenced the levels of Ngb and Hif-1α. Immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and Western blot (WB) were employed to investigate the expression of Ngb and Hif-1α in the diencephalon of young yaks. Ngb and Hif-1α are significantly expressed in all tissues of the diencephalon except the hypothalamus and epithalamus. The thalamus, cerebellar cortex, the white matter of the cerebellum, basal ganglia, and cerebrum showed significant levels of expression, and each plays an important role in the diencephalon. The overall expression of Ngb was higher than that of Hif-1α. Both Ngb and Hif-1α participate in oxygen transport throughout the telencephalon and have functions in neuroprotection. The results suggest that Ngb and Hif-1α influence the mechanism of adaptation of young yaks to their high altitude environment. Further studies on the mechanism of adaptation are recommended.

Download Full-text

The last common ancestor of animals lacked the HIF pathway and respired in low-oxygen environments

eLife ◽

10.7554/elife.31176 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 40

Author(s):

Daniel B Mills ◽

Warren R Francis ◽

Sergio Vargas ◽

Morten Larsen ◽

Coen PH Elemans ◽

...

Keyword(s):

Common Ancestor ◽

Hypoxia Inducible Factor ◽

Last Common Ancestor ◽

Low Oxygen ◽

Oxygen Homeostasis ◽

Animal Phyla ◽

Cellular Oxygen ◽

Hif Pathway ◽

Anaerobic Production ◽

Oxygen Concentrations

Animals have a carefully orchestrated relationship with oxygen. When exposed to low environmental oxygen concentrations, and during periods of increased energy expenditure, animals maintain cellular oxygen homeostasis by enhancing internal oxygen delivery, and by enabling the anaerobic production of ATP. These low-oxygen responses are thought to be controlled universally across animals by the hypoxia-inducible factor (HIF). We find, however, that sponge and ctenophore genomes lack key components of the HIF pathway. Since sponges and ctenophores are likely sister to all remaining animal phyla, the last common ancestor of extant animals likely lacked the HIF pathway as well. Laboratory experiments show that the marine sponge Tethya wilhelma maintains normal transcription under oxygen levels down to 0.25% of modern atmospheric saturation, the lowest levels we investigated, consistent with the predicted absence of HIF or any other HIF-like pathway. Thus, the last common ancestor of all living animals could have metabolized aerobically under very low environmental oxygen concentrations.

Download Full-text

Overexpression of Pygo2 Increases Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Cardiomyocyte-like Cells

Current Molecular Medicine ◽

10.2174/1566524019666191017150416 ◽

2020 ◽

Vol 20 (4) ◽

pp. 318-324 ◽

Cited By ~ 3

Author(s):

Lei Yang ◽

Shuoji Zhu ◽

Yongqing Li ◽

Jian Zhuang ◽

Jimei Chen ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Heart Function ◽

Critical Role ◽

Human Umbilical Cord ◽

Stem Cell Markers ◽

Quantitative Real Time Pcr ◽

Qrt Pcr

Background: Our previous studies have shown that Pygo (Pygopus) in Drosophila plays a critical role in adult heart function that is likely conserved in mammals. However, its role in the differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) into cardiomyocytes remains unknown. Objective: To investigate the role of pygo2 in the differentiation of hUC-MSCs into cardiomyocytes. Methods: Third passage hUC-MSCs were divided into two groups: a p+ group infected with the GV492-pygo2 virus and a p− group infected with the GV492 virus. After infection and 3 or 21 days of incubation, Quantitative real-time PCR (qRT-PCR) was performed to detect pluripotency markers, including OCT-4 and SOX2. Nkx2.5, Gata-4 and cTnT were detected by immunofluorescence at 7, 14 and 21 days post-infection, respectively. Expression of cardiac-related genes—including Nkx2.5, Gata-4, TNNT2, MEF2c, ISL-1, FOXH1, KDR, αMHC and α-Actin—were analyzed by qRT-PCR following transfection with the virus at one, two and three weeks. Results : After three days of incubation, there were no significant changes in the expression of the pluripotency stem cell markers OCT-4 and SOX2 in the p+ group hUC-MSCs relative to controls (OCT-4: 1.03 ± 0.096 VS 1, P > 0.05, SOX2: 1.071 ± 0.189 VS 1, P > 0.05); however, after 21 days, significant decreases were observed (OCT-4: 0.164 ± 0.098 VS 1, P < 0.01, SOX2: 0.209 ± 0.109 VS 1, P < 0.001). Seven days following incubation, expression of mesoderm specialisation markers, such as Nkx2.5, Gata-4, MEF2c and KDR, were increased; at 14 days following incubation, expression of cardiac genes, such as Nkx2.5, Gata-4, TNNT2, MEF2c, ISL-1, FOXH1, KDR, αMHC and α-Actin, were significantly upregulated in the p+ group relative to the p− group (P < 0.05). Taken together, these findings suggest that overexpression of pygo2 results in more hUCMSCs gradually differentiating into cardiomyocyte-like cells. Conclusion: We are the first to show that overexpression of pygo2 significantly enhances the expression of cardiac-genic genes, including Nkx2.5 and Gata-4, and promotes the differentiation of hUC-MSCs into cardiomyocyte-like cells.

Download Full-text

Neuromuscular Control of Movement

10.1093/oso/9780198743156.003.0008 ◽

2018 ◽

Keyword(s):

Nervous System ◽

Sensory Information ◽

Neuromuscular Control ◽

Complex Environments ◽

Locomotor Rhythm ◽

Motor Responses ◽

Reflex Pathways ◽

Local Reflex ◽

Local Circuits ◽

And Control

The control of movement is essential for animals traversing complex environments and operating across a range of speeds and gaits. We consider how animals process sensory information and initiate motor responses, primarily focusing on simple motor responses that involve local reflex pathways of feedback and control, rather than the more complex, longer-term responses that require the broader integration of higher centers within the nervous system. We explore how local circuits facilitate decentralized coordination of locomotor rhythm and examine the fundamentals of sensory receptors located in the muscles, tendons, joints, and at the animal’s body surface. These sensors monitor the animal’s physical environment and the action of its muscles. The sensory information is then carried back to the animal’s nervous system by afferent neurons, providing feedback that is integrated at the level of the spinal cord of vertebrates and sensory-motor ganglia of invertebrates.

Download Full-text

Defining the transcriptomic landscape of the developing enteric nervous system and its cellular environment

BMC Genomics ◽

10.1186/s12864-017-3653-2 ◽

2017 ◽

Vol 18 (1) ◽

Cited By ~ 15

Author(s):

Sweta Roy-Carson ◽

Kevin Natukunda ◽

Hsien-chao Chou ◽

Narinder Pal ◽

Caitlin Farris ◽

...

Keyword(s):

Nervous System ◽

Enteric Nervous System ◽

Cellular Environment

Download Full-text

Behavioral Endocrinology: Integrating Mind and Body

Evolutionary Studies in Imaginative Culture ◽

10.26613/esic.4.2.192 ◽

2020 ◽

Vol 4 (2) ◽

pp. 97-110

Author(s):

Peter T. Ellison

Keyword(s):

Nervous System ◽

Steroid Hormones ◽

Behavioral Ecology ◽

Endocrine System ◽

Behavioral Endocrinology ◽

Paternal Behavior ◽

Mind And Body ◽

The Central Nervous System ◽

Primary Focus

Abstract The nervous system and the endocrine system interact to integrate behavior and physiology. Hormones play an important role in this interaction, particularly steroid hormones. Other molecules, notably oxytocin, can serve both as hormones in the soma and neuromodulators in the central nervous system. Understanding the influence of the endocrine system on human behavior, both individual and social, has been a primary focus of behavioral endocrinology for many decades, though technical and methodological challenges have been formidable. The recent enthusiasm for enzyme-linked immunoassay kits for measuring steroid hormones in saliva has been found to be largely unsound, for example. Despite these difficulties, advances in many areas have been made and new areas, such as the endocrinology of paternal behavior and the role of oxytocin in social interactions, have emerged. Reproductive ecology provides a theoretical framework for integrating the diverse content of human behavioral ecology.

Download Full-text

Frequent Abdominal Pain in Childhood and Youth: A Systematic Review of Psychophysiological Characteristics

Gastroenterology Research and Practice ◽

10.1155/2014/524383 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Marco Daniel Gulewitsch ◽

Judith Müller ◽

Paul Enck ◽

Katja Weimer ◽

Juliane Schwille-Kiuntke ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Abdominal Pain ◽

Endocrine System ◽

Gastrointestinal Disorder ◽

Autonomous Nervous System ◽

Journal Articles ◽

Childhood And Youth ◽

Endocrine Parameters ◽

The Central Nervous System

Background. Frequent abdominal pain (AP) in children and adolescents is often designated as functional gastrointestinal disorder. In contrast to research on psychological and social influences on the experience of AP in this population, psychophysiological features such as function of the autonomic nervous system, the central nervous system, or the endocrine system have rarely been studied.Methods. We conducted a systematic literature search for peer-reviewed journal articles referring to children with AP between 4 and 18 years. Studies on experimental baseline characteristics or reactivity of psychophysiological outcome parameters (autonomous nervous system, central nervous system, and endocrine parameters) were included.Key Results. Twelve of 18 included studies found psychophysiological differences between children with AP and healthy ones. These studies indicate a possible autonomic dysregulation and hypersensitivity of the central nervous system in children with AP following stimulation with stress or other intense stimuli. Mainly conflicting results were found regarding baseline comparisons of autonomic and endocrine parameters.Conclusions and Inferences. Frequent AP in children may be associated with an altered psychophysiological reaction on intense stimuli. It has to be considered that the current literature on psychophysiological characteristics of childhood AP is small and heterogeneous. In particular, multiparameter studies using validated experimental paradigms are lacking.

Download Full-text

Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis

Blood ◽

10.1182/blood-2009-05-189985 ◽

2009 ◽

Vol 114 (10) ◽

pp. 2015-2019 ◽

Cited By ~ 136

Author(s):

Gregg L. Semenza

Keyword(s):

Blood Cells ◽

Tissue Oxygenation ◽

Hypoxia Inducible Factor ◽

Α Subunit ◽

Vhl Gene ◽

Von Hippel Lindau ◽

Hypoxia Inducible Factor 1 ◽

Oxygen Homeostasis ◽

Genes Encoding ◽

Asparaginyl Hydroxylase

Abstract Red blood cells deliver O2 from the lungs to every cell in the human body. Reduced tissue oxygenation triggers increased production of erythropoietin by hypoxia-inducible factor 1 (HIF-1), which is a transcriptional activator composed of an O2-regulated α subunit and a constitutively expressed β subunit. Hydroxylation of HIF-1α or HIF-2α by the asparaginyl hydroxylase FIH-1 blocks coactivator binding and transactivation. Hydroxylation of HIF-1α or HIF-2α by the prolyl hydroxylase PHD2 is required for binding of the von Hippel-Lindau protein (VHL), leading to ubiquitination and proteasomal degradation. Mutations in the genes encoding VHL, PHD2, and HIF-2α have been identified in patients with familial erythrocytosis. Patients with Chuvash polycythemia, who are homozygous for a missense mutation in the VHL gene, have multisystem pathology attributable to dysregulated oxygen homeostasis. Intense efforts are under way to identify small molecule hydroxylase inhibitors that can be administered chronically to selectively induce erythropoiesis without undesirable side effects.

Download Full-text

Ascorbic acid improves parthenogenetic embryo development through TET proteins in mice

Bioscience Reports ◽

10.1042/bsr20181730 ◽

2019 ◽

Vol 39 (1) ◽

Cited By ~ 5

Author(s):

Wei Gao ◽

Xianfeng Yu ◽

Jindong Hao ◽

Ling Wang ◽

Minghui Qi ◽

...

Keyword(s):

Ascorbic Acid ◽

Vitamin C ◽

Embryonic Development ◽

Real Time Pcr ◽

Quantitative Real Time Pcr ◽

Qrt Pcr ◽

Tet Proteins ◽

Parthenogenetic Embryo ◽

Blastocyst Rate

Abstract The TET (Ten-Eleven Translocation) proteins catalyze the oxidation of 5mC (5-methylcytosine) to 5hmC (5-hydroxymethylcytosine) and play crucial roles in embryonic development. Ascorbic acid (Vc, Vitamin C) stimulates the expression of TET proteins, whereas DMOG (dimethyloxallyl glycine) inhibits TET expression. To investigate the role of TET1, TET2, and TET3 in PA (parthenogenetic) embryonic development, Vc and DMOG treatments were administered during early embryonic development. The results showed that Vc treatment increased the blastocyst rate (20.73 ± 0.46 compared with 26.57 ± 0.53%). By contrast, DMOG reduced the blastocyst rate (20.73 ± 0.46 compared with 11.18 ± 0.13%) in PA embryos. qRT-PCR (quantitative real-time PCR) and IF (immunofluorescence) staining results revealed that TET1, TET2, and TET3 expressions were significantly lower in PA embryos compared with normal fertilized (Con) embryos. Our results revealed that Vc stimulated the expression of TET proteins in PA embryos. However, treatment with DMOG significantly inhibited the expression of TET proteins. In addition, 5hmC was increased following treatment with Vc and suppressed by DMOG in PA embryos. Taken together, these results indicate that the expression of TET proteins plays crucial roles mediated by 5hmC in PA embryonic development.

Download Full-text

Crosstalk in oxygen homeostasis networks: SKN-1/NRF inhibits the HIF-1 hypoxia-inducible factor in Caenorhabditis elegans

10.1101/2021.03.12.435071 ◽

2021 ◽

Author(s):

Dingxia Feng ◽

Zhiwei Zhai ◽

Zhiyong Shao ◽

Yi Zhang ◽

Jo Anne Powell-Coffman

Keyword(s):

Oxidative Stress ◽

Hypoxia Inducible Factor ◽

Regulatory Sequences ◽

Low Oxygen ◽

Transcriptional Responses ◽

C Elegans ◽

Protein Levels ◽

Oxygen Homeostasis ◽

Genome Wide ◽

A Genome

AbstractDuring development, homeostasis, and disease, organisms must balance responses that allow adaptation to low oxygen (hypoxia) with those that protect cells from oxidative stress. The evolutionarily conserved hypoxia-inducible factors are central to these processes, as they orchestrate transcriptional responses to oxygen deprivation. Here, we employ genetic strategies in C. elegans to identify stress-responsive genes and pathways that modulate the HIF-1 hypoxia-inducible factor and facilitate oxygen homeostasis. Through a genome-wide RNAi screen, we show that RNAi-mediated mitochondrial or proteasomal dysfunction increases the expression of hypoxia-responsive reporter Pnhr-57:GFP in C. elegans. Interestingly, only a subset of these effects requires hif-1. Of particular importance, we found that skn-1 RNAi increases the expression of hypoxia-responsive reporter Pnhr-57:GFP and elevates HIF-1 protein levels. The SKN-1/NRF transcription factor has been shown to promote oxidative stress resistance. We present evidence that the crosstalk between HIF-1 and SKN-1 is mediated by EGL-9, the prolyl hydroxylase that targets HIF-1 for oxygen-dependent degradation. Treatment that induces SKN-1, such as heat, increases expression of a Pegl-9:GFP reporter, and this effect requires skn-1 function and a putative SKN-1 binding site in egl-9 regulatory sequences. Collectively, these data support a model in which SKN-1 promotes egl-9 transcription, thereby inhibiting HIF-1. We propose that this interaction enables animals to adapt quickly to changes in cellular oxygenation and to better survive accompanying oxidative stress.

Download Full-text

Imagination der Bewegung durch Vibrationsreize – ein neuer Ansatz in der Frühmobilisation auf der Intensivstation?

Neurologie & Rehabilitation ◽

10.14624/nr2011003 ◽

2020 ◽

Vol 26 (4) ◽

pp. 214-218

Author(s):

M. Lippert-Grüner ◽

B. Bakaláø ◽

R. Zajíèek ◽

F. Duška

Keyword(s):

Nervous System ◽

Intensive Care ◽

Pilot Study ◽

Sensory Information ◽

Early Mobilization ◽

Motor Units ◽

The Body ◽

Entire Body ◽

Vibration Effect ◽

Illusory Movement

Zusammenfassung Die Optimierung der motorischen Leistung und die Einbindung und Vernetzung bisher nicht verwendeter motorischer Einheiten sowie die vermehrte Ausschüttung neurotropher Faktoren sind zentrale Mechanismen der Vibrationswirkung, die therapeutisch auf einzelne Körperteile oder den gesamten Körper angewendet werden können. Eine Möglichkeit, die Frühmobilisation bei kritisch kranken Patienten effektiver zu gestalten und immobilitätsbedingten Veränderungen vorzubeugen, könnte die Verwendung des Vibramoov™-Systems sein. Gezielt programmierte Vibrationssequenzen stimulieren hier das Nervensystem mit sensorischen Informationen, die die Empfindung einer Bewegung nachahmen (z. B. des Gehens) und somit Regenerations- und Reor-ganisationsprozesse im zentralen Nervensystem unterstützen können. Von Bedeutung ist dieser Therapieansatz vor allem bei Patienten, bei denen aufgrund ihres Zustandes konventionelle Maßnahmen nicht oder nur eingeschränkt durchgeführt werden können. Da bisher keine Erfah-rungen zur Anwendung bei intensivpflichtigen Patienten verfügbar sind, wurde eine Pilotstudie durchgeführt mit der Fragestellung, ob diese Therapieform sicher ist und im normalen Betrieb auf der Intensivstation verwendet werden kann. Die Ergebnisse der Pilotstudie mit fünf Patienten zei-gen, dass die Anwendung von Vibramoov™ zu keiner wesentlichen Veränderung kardiopulmo-naler Parameter im Sinne einer Non-Toleranz führte und im klinischen Setting gut umsetzbar war. Schlüsselwörter: Frührehabilitation, Imagination von Bewegung, Intensivstation, Vibramoov™ Imagination of movement through vibrational stimuli – a new approach to early mobilization in intensive care units? A pilot study Abstract The optimization of motor performance and the integration and networking of previously unused motor units, as well as the increased release of neurotrophic factors, are central mechanisms related to the vibration effect that can be applied therapeutically to individual parts of the body or to the entire body. One way to make early mobilization more effective in critically ill patients and to prevent changes due to immobility could be rehabilitation with functional proprioceptive stimulation, also known as “illusory movement”. Specifically programmed vibration sequences stimulate the nervous system with sensory information that mimics the sensation of movement (e. g., walking) and can thus support regeneration and reorganization processes in the central nervous system. This therapeutic approach is particularly important for patients who, due to their condition, cannot – or only to a limited extent – carry out conventional measures. Since no experience has so far been available for use in intensive care patients, we carried out a pilot study to answer the question of whether this form of therapy can be used safely and in normal operations in the intensive care unit. The results of the pilot study with 5 patients showed that the use of Vibramoov™ did not lead to any significant change in cardiopulmonary parameters in terms of non-tolerance and was easy to implement in a clinical setting. Keywords: early rehabilitation, illusory movements, ICU, functional proprio-ceptive stimulation

Download Full-text