scholarly journals Omega-3 PUFAs Suppress IL-1β-Induced Hyperactivity of Immunoproteasomes in Astrocytes

2021 ◽  
Vol 22 (11) ◽  
pp. 5410
Author(s):  
Emilia Zgorzynska ◽  
Barbara Dziedzic ◽  
Monika Markiewicz ◽  
Anna Walczewska
Keyword(s):  
Connexin 43 ◽  
Regulatory Element ◽  
Dependent Manner ◽  
Omega 3 ◽  
Junction Protein ◽  
Proteasome Subunits ◽  
Gap Junction Protein ◽  
Dose Dependent ◽  
The Brain

The role of immunoproteasome (iP) in astroglia, the cellular component of innate immunity, has not been clarified. The results so far indicate that neuroinflammation, a prominent hallmark of Alzheimer’s disease, strongly activates the iP subunits expression. Since omega-3 PUFAs possess anti-inflammatory and pro-resolving activity in the brain, we investigated the effect of DHA and EPA on the gene expression of constitutive (β1 and β5) and inducible (iβ1/LMP2 and iβ5/LMP7) proteasome subunits and proteasomal activity in IL-1β-stimulated astrocytes. We found that both PUFAs downregulated the expression of IL-1β-induced the iP subunits, but not the constitutive proteasome subunits. The chymotrypsin-like activity was inhibited in a dose-dependent manner by DHA, and much strongly in the lower concentration by EPA. Furthermore, we established that C/EBPα and C/EBPβ transcription factors, being the cis-regulatory element of the transcription complex, frequently activated by inflammatory mediators, participate in a reduction in the iP subunits’ expression. Moreover, the expression of connexin 43 the major gap junction protein in astrocytes, negatively regulated by IL-1β was markedly increased in PUFA-treated cells. These findings indicate that omega-3 PUFAs attenuate inflammation-induced hyperactivity of iPs in astrocytes and have a beneficial effect on preservation of interastrocytic communication by gap junctions.

scholarly journals Effect of γ-ethyl-γ-phenyl-butyrolactone (EFBL), anticonvulsant and hypnotic drug, on mouse brain catecholamine levels

2017 ◽  
Vol 67 (2) ◽  
pp. 215-226 ◽  
Author(s):  
Lourdes A. Vega Rasgado ◽  
Iván Villanueva ◽  
Fernando Vega Díaz
Keyword(s):  
Seizure Activity ◽  
Refractory Epilepsy ◽  
Aminooxyacetic Acid ◽  
Dependent Manner ◽  
Dopaminergic Receptors ◽  
Hypnotic Drug ◽  
Brain Levels ◽  
Dose Dependent ◽  
The Brain

Abstractγ-Ethyl-γ-phenyl-butyrolactone (EFBL) is a structural combination of the anticonvulsant γ-hydroxy-γ-ethyl-γ-phenylbutyramide (HEPB) and the hypnotic γ-butyrolactone (GBL), which inherits both properties. To clarify its mechanism of action, the effects of EFBL, GBL and HEPB on dopamine (DA) and noradrenaline (NA) brain levels were investigated. Influences of chlorpromazine, phenelzine and aminooxyacetic acid were also studied. EFBL increased DA in a dose-dependent manner, remaining enhanced by 80 % over a period of 24 h and augmented NA by 54 % one hour after treatment. HEPB increased DA and NA approximately 2-fold after the first hour. GBL raised DA and NA after three and 24 h, resp. EFBL reversed chlorpromazine effects but potentiated those of phenelzine on DA. Amino-oxyacetic modified neither DA nor NA brain levels, not even in the presence of EFBL. The anticonvulsant and hypnotic properties of EFBL are attributed to its effect on presynaptic dopaminergic receptors and its lasting effect on ethyl and phenyl radicals that hinder its degradation. The results support the role of DA and NA in regulating seizure activity in the brain and indicate that EFBL offers a potential treatment for refractory epilepsy without complementary drugs and Parkinson’s disease, without the drawbacks of oral therapies.

Omega-3 fatty acids and atorvastatin affect connexin 43 expression in the aorta of hereditary hypertriglyceridemic ratsThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.

2009 ◽  
Vol 87 (12) ◽  
pp. 1074-1082 ◽  
Author(s):  
Katarína Dlugošová ◽  
Peter Weismann ◽  
Iveta Bernátová ◽  
Ružena Sotníková ◽  
Ján Slezák ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Connexin 43 ◽  
Structural Integrity ◽  
Disease Incidence ◽  
Omega 3 ◽  
Cardiovascular Research ◽  
Cx43 Expression ◽  
Junction Protein ◽  
Effect Of Treatment ◽  
Gap Junction Protein

Statins and omega-3 polyunsaturated fatty acids (n-3 PUFA) reduce cardiovascular disease incidence during hypertriglyceridemia (HTG). To elucidate possible cardioprotective mechanisms, we focused on gap junction protein connexin 43 (Cx43). Its expression is disturbed during atherogenesis, but little information is available on its expression during HTG. Experiments were performed on adult male hereditary HTG (hHTG) rats treated with n-3 PUFA (30 mg/day) and atorvastatin (0.5 mg/100 g body weight per day) for 2 months. Cx43 expression and distribution in the aorta were investigated by using Western blotting and immunolabeling, followed by quantitative analysis. Transmission electronmicroscopy was used to study ultrastructure of endothelial contact sites. In contrast to age-matched Wistar, Cx43 expression in aorta of hHTG rats was significantly higher (p < 0.05), and prominent Cx43 immunospots were seen in tunica media and less in endothelium of hHTG rats. Changes in Cx43 expression were accompanied by local qualitative subcellular alterations of interendothelial connections. Treatment of hHTG rats with n-3 PUFA and atorvastatin markedly lowered Cx43 expression in aorta and modified connexin distribution in endothelium and media (p < 0.05 vs. untreated hHTG). The protective effect of treatment of HTG was observed on the structural integrity of the endothelium and was readily visible at the molecular level. Results indicate the involvement of altered Cx43 expression in vascular pathophysiology during HTG and during HTG treatment.

scholarly journals Role of Connexin 43 in an Inflammatory Model for TMJ Hyperalgesia

2021 ◽  
Vol 2 ◽  
Author(s):  
Fabeeha Ahmed ◽  
Md. Rahman ◽  
Randall Thompson ◽  
David A. Bereiter
Keyword(s):  
Temporomandibular Joint ◽  
Connexin 43 ◽  
Temporomandibular Joint Disorders ◽  
Female Rats ◽  
Dependent Manner ◽  
Cx43 Expression ◽  
Cx43 Protein ◽  
Junction Protein ◽  
Males And Females

Temporomandibular joint disorders (TMD) consist of a heterogeneous group of conditions that present with pain in the temporomandibular joint (TMJ) region and muscles of mastication. This project assessed the role of connexin 43 (Cx43), a gap junction protein, in the trigeminal ganglion (TG) in an animal model for persistent inflammatory TMJ hyperalgesia. Experiments were performed in male and female rats to determine if sex differences influence the expression and/or function of Cx43 in persistent TMJ hyperalgesia. Intra-TMJ injection of Complete Freund's Adjuvant (CFA) caused a significant increase in Cx43 expression in the TG at 4 days and 10 days post-injection in ovariectomized (OvX) female rats and OvX females treated with estradiol (OvXE), while TG samples in males revealed only marginal increases. Intra-TG injection of interference RNA for Cx43 (siRNA Cx43) 3 days prior to recording, markedly reduced TMJ-evoked masseter muscle electromyographic (MMemg) activity in all CFA-inflamed rats, while activity in sham animals was not affected. Western blot analysis revealed that at 3 days after intra-TG injection of siRNA Cx43 protein levels for Cx43 were significantly reduced in TG samples of all CFA-inflamed rats. Intra-TG injection of the mimetic peptide GAP19, which inhibits Cx43 hemichannel formation, greatly reduced TMJ-evoked MMemg activity in all CFA-inflamed groups, while activity in sham groups was not affected. These results revealed that TMJ inflammation caused a persistent increase in Cx43 protein in the TG in a sex-dependent manner. However, intra-TG blockade of Cx43 by siRNA or by GAP19 significantly reduced TMJ-evoked MMemg activity in both males and females following TMJ inflammation. These results indicated that Cx43 was necessary for enhanced jaw muscle activity after TMJ inflammation in males and females, a result that could not be predicted on the basis of TG expression of Cx43 alone.

scholarly journals Spontaneous REM Sleep Is Modulated By the Activation of the Pedunculopontine Tegmental GABAB Receptors in the Freely Moving Rat

2004 ◽  
Vol 91 (4) ◽  
pp. 1822-1831 ◽  
Author(s):  
Jagadish Ulloor ◽  
Vijayakumar Mavanji ◽  
Subhash Saha ◽  
Donald F. Siwek ◽  
Subimal Datta
Keyword(s):  
Rem Sleep ◽  
Gabab Receptors ◽  
Optimum Dose ◽  
Dependent Manner ◽  
Specific Receptors ◽  
Cholinergic Cell ◽  
Freely Moving ◽  
Dose Dependent ◽  
The Brain

Considerable evidence suggests that the neurotransmitter γ-aminobutyric acid (GABA)-ergic system and pedunculopontine tegmentum (PPT) in the brain stem are critically involved in the regulation of rapid-eye-movement (REM) sleep. GABA and its various receptors are normally present in the PPT cholinergic cell compartment. The aim of this study was to identify the role of GABA and its receptors in the regulation of REM sleep. To achieve this aim, specific receptors were activated differentially by local microinjection of selective GABA receptor agonists into the PPT while quantifying its effects on REM sleep in freely moving chronically instrumented rats ( n = 21). The results demonstrated that when GABAB receptors were activated by local microinjection of a GABAB receptor selective agonist, baclofen, spontaneous REM sleep was suppressed in a dose-dependent manner. The optimum dose for REM sleep reduction was 1.5 nmol. In contrast, when GABAA and GABAC receptors were activated by microinjecting their receptor selective agonists, isoguvacine (ISGV) and cis-4-aminocrotonic acid (CACA), respectively, the total percentages of REM sleep did not change compared with the control values. In another eight freely moving rats, effects of baclofen application was tested on firing rates of REM-on cells ( n = 12). Of those 12 neurons, 11 stopped firing immediately after application of baclofen [latency: 50 ± 14 s (SD)] and remained almost silent for 130 ± 12 min. Findings of the present study provide direct evidence that the PPT GABAB receptors and REM-on cells are involved in the regulation of REM sleep.

scholarly journals The role of nesfatin-1 in metabolism regulation: an overview / Rola nesfatyny-1 w regulacji metabolizmu: artykuł przeglądowy

2013 ◽  
Vol 13 (2) ◽  
pp. 195-205
Author(s):  
Michał Bulc ◽  
Sławomir Gonkowski ◽  
Jarosław Całka
Keyword(s):  
Body Weight Gain ◽  
Wide Distribution ◽  
Dark Phase ◽  
Dependent Manner ◽  
Peripheral Tissues ◽  
Functional Studies ◽  
Metabolism Regulation ◽  
Dose Dependent ◽  
The Brain

Abstract The hypothalamus synthesizes molecules involved in the regulation of feeding behaviour. Nesfatin- 1 is a recently discovered substance expressed in both the brain and peripheral tissues and exerts a strong anorectic action. Nesfatin-1-immunoreactive cell bodies are distributed in arcuate (ARC), paraventricular (PVN) and supraoptic (SON) nuclei, where the peptide has been found to be co-expressed with pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART), oxytocin (OX) and vasopressin (VP). More detailed studies have shown a wide distribution of nesfatin-1-positive neurons in several brain areas, such as the forebrain, hindbrain, brainstem and spinal cord. Moreover, nesfatin-1 has been also expressed in peripheral tissues, colocalizing with ghrelin in the gastric mucosa and insulin in β-cells of the endocrine pancreas and adipose tissue. Functional studies have revealed that exogenous nesfatin-1 administered into the brain ventricles, subcutaneously or intraperitoneally, was able to decrease both food intake in the dark phase as well as body weight gain in a dose-dependent manner. In addition, recent findings suggest the involvement of nesfatin-1 in the control of insulin secretion as well as immune and stress-related responses. However, since there is still a deficiency of data concerning the nesfatin-1 receptor, the possible implementation of nesfatin-1 analogs during human metabolic disorders requires further study.

scholarly journals Role of Bcl2-associated Athanogene 3 in Turnover of Gap Junction Protein, Connexin 43, in Neonatal Cardiomyocytes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Farzaneh Ghasemi Tahrir ◽  
Manish Gupta ◽  
Valerie Myers ◽  
Jennifer Gordon ◽  
Joseph Y. Cheung ◽  
...  
Keyword(s):  
Gap Junction ◽  
Connexin 43 ◽  
Neonatal Cardiomyocytes ◽  
Junction Protein ◽  
Gap Junction Protein

scholarly journals Dose-related effects of clozapine and risperidone on the pattern of brain regional serotonin and dopamine metabolism and on tests related to extrapyramidal functions in rats

2010 ◽  
Vol 60 (2) ◽  
pp. 129-140 ◽  
Author(s):  
Farhat Batool ◽  
Ambreen Hasnat ◽  
Muhammad Haleem ◽  
Darakhshan Haleem
Keyword(s):  
Dopamine Metabolism ◽  
High Dose ◽  
Dependent Manner ◽  
Saline Administration ◽  
Hydroxyindoleacetic Acid ◽  
High Doses ◽  
Home Cage Activity ◽  
Dose Dependent ◽  
The Brain

Dose-related effects of clozapine and risperidone on the pattern of brain regional serotonin and dopamine metabolism and on tests related to extrapyramidal functions in rats The present study was designed to evaluate the behavioral and neurochemical profiles of clozapine and risperidone in rats in a dose-dependent manner. Animals injected intraperitoneally (i.p.) with clozapine (2.5, 5.0 and 10.0 mg kg-1) or risperidone (1.0, 2.5 and 5.0 mg kg-1) were sacrificed 1 h later to collect brain samples. Hypolocomotive effects (home cage activity and catalepsy) were successively monitored in each animal after the drug or saline administration. Both drugs significantly (p < 0.01) decreased locomotor activity at high doses and in a dose-dependent manner. Maximum (100%) cataleptic potential was achieved at a high dose (5.0 mg kg-1) of risperidone. Neurochemical estimations were carried out by HPLC with electrochemical detection. Both drugs, at all doses, significantly (p < 0.01) increased the concentration of homovanillic acid (HVA), a metabolite of dopamine (DA), in the striatum. Dihydroxyphenylacetic acid (DOPAC) levels increased in the striatum and decreased in the rest of the brain, particularly in clozapine-injected rats. 5-Hydroxyindoleacetic acid (5-HIAA), the predominant metabolite of serotonin, significantly (p < 0.01) decreased in the striatum. 5-Hydroxytryptamine (5-HT) was significantly (p < 0.01) increased by risperidone and decreased by clozapine in the rest of the brain. Striatal tryptophan (TRP) was significantly (p < 0.01) decreased by risperidone and increased in the rest of the brain. The striatal HVA/DA ratio increased and the 5-HT turnover rate remained unchanged in the rest of the brain. Results suggest that the affinity of the two drugs towards D2/5-HT1A receptors interaction is involved in lower incidence of extrapyramidal side effects. Role of 5-HT1A receptors in the treatment of schizophrenia is discussed.

Amelioration of Carbon Tetrachloride-Induced Liver Injury by Citrus Leaf Extract

2019 ◽  
Vol 17 (4) ◽  
pp. 426-431
Author(s):  
Jin Xuezhu ◽  
Li Jitong ◽  
Nie Leigang ◽  
Xue Junlai
Keyword(s):  
Carbon Tetrachloride ◽  
Leaf Extract ◽  
Hepatic Injury ◽  
The Body ◽  
Dependent Manner ◽  
Weight Changes ◽  
Citrus Leaf ◽  
Dose Dependent ◽  
And Oxidative Stress

The main purpose of this study is to investigate the role of citrus leaf extract in carbon tetrachloride-induced hepatic injury and its potential molecular mechanism. Carbon tetrachloride was used to construct hepatic injury animal model. To this end, rats were randomly divided into 4 groups: control, carbon tetrachloride-treated, and two carbon tetrachloride + citrus leaf extract-treated groups. The results show that citrus leaf extract treatment significantly reversed the effects of carbon tetrachloride on the body weight changes and liver index. Besides, treatment with citrus leaf extract also reduced the levels of serum liver enzymes and oxidative stress in a dose-dependent manner. H&E staining and western blotting suggested that citrus leaf extract could repair liver histological damage by regulating AMPK and Nrf-2.

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