scholarly journals Comparative Transcriptomic Analysis of the Brain in Takifugu Rubripes Shows Its Tolerance to Acute Hypoxia

2021 ◽  
Author(s):  
Mingxiu Bao ◽  
Fengqin Shang ◽  
Fujun Liu ◽  
Ziwen Hu ◽  
Shengnan Wang ◽  
...  
Keyword(s):  
Acute Hypoxia ◽  
Enrichment Analysis ◽  
Takifugu Rubripes ◽  
Low Oxygen ◽  
Short Term ◽  
Protection Mechanism ◽  
Complete Set ◽  
Self Protection ◽  
The Brain ◽  
Comparative Transcriptomic Analysis

Abstract Hypoxia is reduced levels of oxygen. Especially in water, due to the complex environment, hypoxic situations often occur. Although fish can survive in low-oxygen waters, this survival ability depends on a complete set of coping mechanisms such as oxygen perception and gene-protein interaction regulation. The research on this mechanism is very meaningful. The present study was undertaken to examine the short-term effects of hypoxia on the brain in Takifugu rubripes. We sequenced the transcriptomes of the brain in T. rubripes to studied their response mechanism to acute hypoxia. Total 167 genes with adjusted P values<0.05 were differentially expressed in the brain of T. rubripes exposed to acute hypoxia. However, hif1a, the master transcriptional regulator of the adaptive response to hypoxia, was not significantly regulated, which indicated that the T. rubripes brain might prevent the HIF-1 signaling pathway. Then Gene Ontology and KEGG Enrichment Analysis were carried out. The results indicated that hypoxia could cause metabolic and neurological changes, showing the clues of their adaptation to acute hypoxia. Overall, the sequenced transcriptomes of the brain in T. rubripes showed small changes under acute hypoxia. As the most complex and important organ, the brain of T. rubripes might be able to create a self-protection mechanism to resist or reduce damage caused by acute hypoxia stress.

Adaptation to hypobaric hypoxia involves GABAA receptors in the pons

2008 ◽  
Vol 294 (2) ◽  
pp. R549-R557 ◽  
Author(s):  
Yee-Hsee Hsieh ◽  
Thomas E. Dick ◽  
Ruth E. Siegel
Keyword(s):  
Brain Stem ◽  
Hypobaric Hypoxia ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Acute Hypoxia ◽  
Receptor Expression ◽  
Dependent Manner ◽  
Low Oxygen ◽  
Subunit Expression ◽  
The Brain

Survival in low-oxygen environments requires adaptation of sympathorespiratory control networks located in the brain stem. The molecular mechanisms underlying adaptation are unclear. In naïve animals, acute hypoxia evokes increases in phrenic (respiratory) and splanchnic (sympathetic) nerve activities that persist after repeated challenges (long-term facilitation, LTF). In contrast, our studies show that conditioning rats to chronic hypobaric hypoxia (CHH), an environment characteristic of living at high altitude, diminishes the response to hypoxia and attenuates LTF in a time-dependent manner. Phrenic LTF decreases following 7 days of CHH, and both sympathetic and phrenic LTF disappear following 14 days of CHH. Previous studies demonstrated that GABA is released in the brain stem during hypoxia and depresses respiratory activity. Furthermore, the sensitivity of brain stem neurons to GABA is increased following prolonged hypoxia. In this study, we demonstrate that GABAA receptor expression changes along with the CHH-induced physiological changes. Expression of the GABAA receptor α4 subunit mRNA increases two-fold in animals conditioned to CHH for 7 days. In addition, de novo expression of δ and α6, a subunit normally found exclusively in the cerebellum, is observed after 14 days. Consistent with these changes, diazepam-insensitive binding sites, characteristic of GABAA receptors containing α4 and α6 subunits, increase in the pons. Immunohistochemistry revealed that CHH-induced GABAA receptor subunit expression is localized in regions of sympathorespiratory control within the pons. Our findings suggest that a GABAA receptor mediated-mechanism participates in adaptation of the sympathorespiratory system to hypobaric hypoxia.

Polychlorinated biphenyl induced hepatocyte alterations

1987 ◽  
Vol 45 ◽  
pp. 716-717
Author(s):  
D.N. Collins ◽  
J.N. Turner ◽  
K.O. Brosch ◽  
R.F. Seegal
Keyword(s):  
Lipid Droplets ◽  
Wistar Rats ◽  
Homovanillic Acid ◽  
Polychlorinated Biphenyl ◽  
Corn Oil ◽  
Environmental Pollutants ◽  
Short Term ◽  
Pcb Congeners ◽  
Urinary Levels ◽  
The Brain

Polychlorinated biphenyls (PCBs) are a ubiquitous class of environmental pollutants with toxic and hepatocellular effects, including accumulation of fat, proliferated smooth endoplasmic recticulum (SER), and concentric membrane arrays (CMAs) (1-3). The CMAs appear to be a membrane storage and degeneration organelle composed of a large number of concentric membrane layers usually surrounding one or more lipid droplets often with internalized membrane fragments (3). The present study documents liver alteration after a short term single dose exposure to PCBs with high chlorine content, and correlates them with reported animal weights and central nervous system (CNS) measures. In the brain PCB congeners were concentrated in particular regions (4) while catecholamine concentrations were decreased (4-6). Urinary levels of homovanillic acid a dopamine metabolite were evaluated (7).Wistar rats were gavaged with corn oil (6 controls), or with a 1:1 mixture of Aroclor 1254 and 1260 in corn oil at 500 or 1000 mg total PCB/kg (6 at each level).

Morphological Changes in the Brain of Acutely Ill and Weight-Recovered Patients with Anorexia Nervosa

2014 ◽  
Vol 42 (1) ◽  
pp. 7-18 ◽  
Author(s):  
Jochen Seitz ◽  
Katharina Bühren ◽  
Georg G. von Polier ◽  
Nicole Heussen ◽  
Beate Herpertz-Dahlmann ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Cognitive Deficits ◽  
Time Course ◽  
Morphological Changes ◽  
Meta Analysis ◽  
Short Term ◽  
Clinical Prognosis ◽  
Qualitative Review ◽  
Brain Changes ◽  
The Brain

Objective: Acute anorexia nervosa (AN) leads to reduced gray (GM) and white matter (WM) volume in the brain, which however improves again upon restoration of weight. Yet little is known about the extent and clinical correlates of these brain changes, nor do we know much about the time-course and completeness of their recovery. Methods: We conducted a meta-analysis and a qualitative review of all magnetic resonance imaging studies involving volume analyses of the brain in both acute and recovered AN. Results: We identified structural neuroimaging studies with a total of 214 acute AN patients and 177 weight-recovered AN patients. In acute AN, GM was reduced by 5.6% and WM by 3.8% compared to healthy controls (HC). Short-term weight recovery 2–5 months after admission resulted in restitution of about half of the GM aberrations and almost full WM recovery. After 2–8 years of remission GM and WM were nearly normalized, and differences to HC (GM: –1.0%, WM: –0.7%) were no longer significant, although small residual changes could not be ruled out. In the qualitative review some studies found GM volume loss to be associated with cognitive deficits and clinical prognosis. Conclusions: GM and WM were strongly reduced in acute AN. The completeness of brain volume rehabilitation remained equivocal.

scholarly journals Expression Analysis of Zinc Transporters in Nervous Tissue Cells Reveals Neuronal and Synaptic Localization of ZIP4

2021 ◽  
Vol 22 (9) ◽  
pp. 4511
Author(s):  
Chiara A. De Benedictis ◽  
Claudia Haffke ◽  
Simone Hagmeyer ◽  
Ann Katrin Sauer ◽  
Andreas M. Grabrucker
Keyword(s):  
Brain Function ◽  
Zinc Homeostasis ◽  
Zinc Transporters ◽  
Excitatory Synapses ◽  
Short Term ◽  
Synaptic Localization ◽  
Zinc Levels ◽  
Rat Astrocyte ◽  
Cellular Zinc ◽  
The Brain

In the last years, research has shown that zinc ions play an essential role in the physiology of brain function. Zinc acts as a potent neuromodulatory agent and signaling ions, regulating healthy brain development and the function of both neurons and glial cells. Therefore, the concentration of zinc within the brain and its cells is tightly controlled. Zinc transporters are key regulators of (extra-) cellular zinc levels, and deregulation of zinc homeostasis and zinc transporters has been associated with neurodegenerative and neuropsychiatric disorders. However, to date, the presence of specific family members and their subcellular localization within brain cells have not been investigated in detail. Here, we analyzed the expression of all zinc transporters (ZnTs) and Irt-like proteins (ZIPs) in the rat brain. We further used primary rat neurons and rat astrocyte cell lines to differentiate between the expression found in neurons or astrocytes or both. We identified ZIP4 expressed in astrocytes but significantly more so in neurons, a finding that has not been reported previously. In neurons, ZIP4 is localized to synapses and found in a complex with major postsynaptic scaffold proteins of excitatory synapses. Synaptic ZIP4 reacts to short-term fluctuations in local zinc levels. We conclude that ZIP4 may have a so-far undescribed functional role at excitatory postsynapses.

scholarly journals Connectivity Map Analysis Indicates PI3K/Akt/mTOR Inhibitors as Potential Anti-Hypoxia Drugs in Neuroblastoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2809
Author(s):  
Paolo Uva ◽  
Maria Carla Bosco ◽  
Alessandra Eva ◽  
Massimo Conte ◽  
Alberto Garaventa ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Drug Repurposing ◽  
Enrichment Analysis ◽  
Mtor Inhibitors ◽  
Gene Set Enrichment Analysis ◽  
Low Oxygen ◽  
Connectivity Map ◽  
Hypoxic Conditions ◽  
Connectivity Score

Neuroblastoma (NB) is one of the deadliest pediatric cancers, accounting for 15% of deaths in childhood. Hypoxia is a condition of low oxygen tension occurring in solid tumors and has an unfavorable prognostic factor for NB. In the present study, we aimed to identify novel promising drugs for NB treatment. Connectivity Map (CMap), an online resource for drug repurposing, was used to identify connections between hypoxia-modulated genes in NB tumors and compounds. Two sets of 34 and 21 genes up- and down-regulated between hypoxic and normoxic primary NB tumors, respectively, were analyzed with CMap. The analysis reported a significant negative connectivity score across nine cell lines for 19 compounds mainly belonging to the class of PI3K/Akt/mTOR inhibitors. The gene expression profiles of NB cells cultured under hypoxic conditions and treated with the mTORC complex inhibitor PP242, referred to as the Mohlin dataset, was used to validate the CMap findings. A heat map representation of hypoxia-modulated genes in the Mohlin dataset and the gene set enrichment analysis (GSEA) showed an opposite regulation of these genes in the set of NB cells treated with the mTORC inhibitor PP242. In conclusion, our analysis identified inhibitors of the PI3K/Akt/mTOR signaling pathway as novel candidate compounds to treat NB patients with hypoxic tumors and a poor prognosis.

scholarly journals Is High Blood Pressure Self-Protection for the Brain?

2016 ◽  
Vol 119 (12) ◽  
Author(s):  
Esther A.H. Warnert ◽  
Jonathan C.L. Rodrigues ◽  
Amy E. Burchell ◽  
Sandra Neumann ◽  
Laura E.K. Ratcliffe ◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Blood Pressure ◽  
Self Protection ◽  
The Brain

Changes of PACAP levels in the brain show gender differences following short-term water and food deprivation

2007 ◽  
Vol 152 (2-3) ◽  
pp. 225-230 ◽  
Author(s):  
P. Kiss ◽  
D. Reglődi ◽  
A. Tamás ◽  
A. Lubics ◽  
I. Lengvári ◽  
...  
Keyword(s):  
Gender Differences ◽  
Food Deprivation ◽  
Short Term ◽  
The Brain

Evaluation of the activity of antihypoxants with an isothiourea structure in a model of hypercapnic hypoxia with a shutdown of the cerebral hemispheres

2021 ◽  
Vol 19 (1) ◽  
pp. 55-63
Author(s):  
Vera V. Marysheva ◽  
Vladimir V. Mikheev ◽  
Petr D. Shabanov
Keyword(s):  
Acute Hypoxia ◽  
Life Time ◽  
The Body ◽  
Cerebral Hemispheres ◽  
Antihypoxic Activity ◽  
Hypoxic Episode ◽  
Hypoxia With Hypercapnia ◽  
Hypercapnic Hypoxia ◽  
Outbred Mice ◽  
The Brain

PURPOSE: To study the effect of amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) on the resistance of male outbred mice to acute hypoxia with hypercapnia under conditions of isolated functioning of one from the hemispheres, as well as both hemispheres of the brain. METHODS: A model of acute hypoxia with hypercapnia (canned hypoxia) was used in mice of the same mass, the lifespan of all animals was determined. Temporary shutdown of the cortex of one of the hemispheres or both hemispheres was achieved by epidural application of filter paper moistened with 25% potassium chloride solution, creating a spreading depression according to Leao. Amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) at equimolar doses of 25, 32.5, and 50 mg/kg, respectively were used as pharmacological analyzers, the compounds were injected intraperitoneally 30 min before the hypoxic episode. RESULTS: It was shown that, in contrast to amtizol, 2-ABT and VM-606 increase the life time of experimental animals when any hemisphere is turned off. The use of drugs when both hemispheres were turned off revealed that amtizol has approximately equal effect on the brain and the rest of the body, in 2-ABT antihypoxic activity is 1/3 associated with the brain, in VM-606 exclusively with the brain. CONCLUSION: The experimental model used in this work makes it possible to quite easily evaluate the effect of either one drug or compare several drugs, their role in the functioning of the cerebral hemispheres, on which part of the sample highly resistant or low resistant to hypoxia they have the greatest effect.

Short-term intermittent hypoxia enhances sympathetic responses to continuous hypoxia in humans

2007 ◽  
Vol 103 (3) ◽  
pp. 835-842 ◽  
Author(s):  
Urs A. Leuenberger ◽  
Cynthia S. Hogeman ◽  
Sadeq Quraishi ◽  
Latoya Linton-Frazier ◽  
Kristen S. Gray
Keyword(s):  
Blood Pressure ◽  
Sleep Apnea ◽  
Sympathetic Activity ◽  
Intermittent Hypoxia ◽  
Muscle Sympathetic Nerve Activity ◽  
Acute Hypoxia ◽  
Short Term ◽  
Healthy Humans ◽  
Obstructive Sleep ◽  
Normal Humans

Short-term intermittent hypoxia leads to sustained sympathetic activation and a small increase in blood pressure in healthy humans. Because obstructive sleep apnea, a condition associated with intermittent hypoxia, is accompanied by elevated sympathetic activity and enhanced sympathetic chemoreflex responses to acute hypoxia, we sought to determine whether intermittent hypoxia also enhances chemoreflex activity in healthy humans. To this end, we measured the responses of muscle sympathetic nerve activity (MSNA, peroneal microneurography) to arterial chemoreflex stimulation and deactivation before and following exposure to a paradigm of repetitive hypoxic apnea (20 s/min for 30 min; O2 saturation nadir 81.4 ± 0.9%). Compared with baseline, repetitive hypoxic apnea increased MSNA from 113 ± 11 to 159 ± 21 units/min ( P = 0.001) and mean blood pressure from 92.1 ± 2.9 to 95.5 ± 2.9 mmHg ( P = 0.01; n = 19). Furthermore, compared with before, following intermittent hypoxia the MSNA (units/min) responses to acute hypoxia [fraction of inspired O2 (FiO2) 0.1, for 5 min] were enhanced (pre- vs. post-intermittent hypoxia: +16 ± 4 vs. +49 ± 10%; P = 0.02; n = 11), whereas the responses to hyperoxia (FiO2 0.5, for 5 min) were not changed significantly ( P = NS; n = 8). Thus 30 min of intermittent hypoxia is capable of increasing sympathetic activity and sensitizing the sympathetic reflex responses to hypoxia in normal humans. Enhanced sympathetic chemoreflex activity induced by intermittent hypoxia may contribute to altered neurocirculatory control and adverse cardiovascular consequences in sleep apnea.

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