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.

Evidence That REM Sleep Is Controlled by the Activation of Brain Stem Pedunculopontine Tegmental Kainate Receptor

2002 ◽  
Vol 87 (4) ◽  
pp. 1790-1798 ◽  
Author(s):  
Subimal Datta
Keyword(s):  
Brain Stem ◽  
Rem Sleep ◽  
Kainate Receptors ◽  
Specific Receptor ◽  
Cell Compartment ◽  
Pharmacological Blockade ◽  
Specific Receptors ◽  
Cholinergic Cell ◽  
First Time ◽  
The Brain

Glutamate, the neurotransmitter, enhances rapid-eye-movement (REM) sleep when microinjected into the brain stem pedunculopontine tegmentum (PPT) of the cat and rat. Glutamate and its various receptors are normally present in the PPT cholinergic cell compartment. The aim of this study was to identify which specific receptor(s) in the cholinergic cell compartment of the PPT are involved in glutamate-induced-REM sleep. To identify these glutamate-induced REM-sleep-generating receptor(s) in the PPT cholinergic cell compartment, specific receptors were pharmacologically blocked differentially by localized pretreatment of specific glutamate receptor antagonists; glutamate was then microinjected into the PPT cholinergic cell compartment while quantifying the effects on REM sleep in freely moving chronically instrumented rats. The results demonstrate that when kainate receptors were blocked by pretreatment with a kainate-specific receptor antagonist, microinjection of glutamate was unable to induce REM sleep. Pharmacological blockade of specific N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors was unable to block glutamate-microinjection-induced-REM sleep. These findings suggest, for the first time, that the activation of kainate receptors within the cholinergic cell compartment of the PPT is an essential portion of the mechanism for the generation of glutamate-induced REM sleep in the rat.

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.

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 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.

Excitation of the Brain Stem Pedunculopontine Tegmentum Cholinergic Cells Induces Wakefulness and REM Sleep

1997 ◽  
Vol 77 (6) ◽  
pp. 2975-2988 ◽  
Author(s):  
Subimal Datta ◽  
Donald F. Siwek
Keyword(s):  
Brain Stem ◽  
Slow Wave ◽  
Rem Sleep ◽  
Slow Wave Sleep ◽  
Cholinergic Neurons ◽  
Dependent Manner ◽  
Cell Compartment ◽  
Recording Time ◽  
Cholinergic Cell ◽  
The Brain

Datta, Subimal and Donald F. Siwek. Excitation of the brain stem pedunculopontine tegmentum cholinergic cells induces wakefulness and REM sleep. J. Neurophysiol. 77: 2975–2988, 1997. Considerable evidence suggests that brain stem pedunculopontine tegmentum (PPT) cholinergic cells are critically involved in the normal regulation of wakefulness and rapid eye movement (REM) sleep. However, much of this evidence comes from indirect studies. Thus, although involvement of PPT cholinergic neurons has been suggested by numerous investigations, the excitation of PPT cholinergic neurons causal to the behavioral state of wakefulness and REM sleep has never been directly demonstrated. In the present study we examined the effects of three different levels of activation of PPT cholinergic cells in wakefulness and sleep behavior. The effects of glutamate on the activity of PPT cholinergic cells were studied by microinjection of one of the three different doses of l-glutamate (0.3, 1.0, and 3.0 μg) or saline (vehicle control) into the PPT cholinergic cell compartment while quantifying the effects on wakefulness and sleep in free moving chronically instrumented cats. All microinjections were made during wakefulness and were followed by 4 h of recording. Polygraphic records were scored for wakefulness, slow-wave sleep states 1 and 2, slow-wave sleep with pontogeniculooccipital waves, and REM sleep. Dependent variables quantified after each microinjection included the percentage of recording time spent in each state, the latency to onset of REM sleep, the number of episodes per hour for REM sleep, and the duration of each REM sleep episode. A total of 48 microinjections was made into 12 PPT sites in six cats. Microinjection of 0.3- and 1.0-μg doses of l-glutamate into the cholinergic cell compartment of the PPT increased the total amount of REM sleep in a dose-dependent manner. Both doses of l-glutamate increased REM sleep at the expense of slow-wave sleep but not wakefulness. Microinjection of 3.0 μg l-glutamate kept animals awake for 2–3 h by eliminating slow-wave and REM sleep. The results show that the microinjection of the excitatory amino acid l-glutamate into the PPT cholinergic cell compartments can increase wakefulness and/or REM sleep depending on the l-glutamate dosage. These findings unambiguously confirm the hypothesis that the excitation of the PPT cholinergic cells is causal to the generation of wakefulness and REM sleep.

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.

Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro

2001 ◽  
Vol 91 (6) ◽  
pp. 2703-2712 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Daniel R. Henderson ◽  
Michael R. Wenninger ◽  
Gordon S. Mitchell
Keyword(s):  
Brain Stem ◽  
Respiratory Activity ◽  
Dependent Manner ◽  
Frequency Increase ◽  
Burst Frequency ◽  
Bath Application ◽  
Burst Amplitude ◽  
Dose Dependent ◽  
The Brain

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.

scholarly journals Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

2021 ◽  
Vol 22 (9) ◽  
pp. 4717
Author(s):  
Jin-Young Lee ◽  
Da-Ae Kim ◽  
Eun-Young Kim ◽  
Eun-Ju Chang ◽  
So-Jeong Park ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Map Kinases ◽  
Osteoclast Differentiation ◽  
Dependent Manner ◽  
Dual Action ◽  
Dose Dependent ◽  
Resorptive Activity

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

Role of extracellular calcium and calmodulin in prolactin secretion induced by hyposmolarity, thyrotropin-releasing hormone, and high K+ in GH4C1 cells

1990 ◽  
Vol 123 (2) ◽  
pp. 218-224 ◽  
Author(s):  
Xiangbing Wang ◽  
Noriyuki Sato ◽  
Monte A. Greer ◽  
Susan E. Greer ◽  
Staci McAdams
Keyword(s):  
Smooth Muscle ◽  
Muscle Relaxant ◽  
Prolactin Secretion ◽  
Thyrotropin Releasing Hormone ◽  
Dependent Manner ◽  
Cell Toxicity ◽  
High K ◽  
Dose Dependent ◽  
Smooth Muscle Relaxant

Abstract. The mechanism by which 30% medium hyposmolarity induces PRL secretion by GH4C1 cells was compared with that induced by 100 nmol/l TRH or 30 mmol/l K+. Removing medium Ca2+, blocking Ca2+ channels with 50 μmol/l verapamil, or inhibiting calmodulin activation with 20 μmol/l trifluoperazine, 10 μmol/l chlorpromazine or 10 μmol/l pimozide almost completely blocked hyposmolarity-induced secretion. The smooth muscle relaxant, W-7, which is believed relatively specific in inhibiting the Ca2+-calmodulin interaction, depressed hyposmolarity-induced PRL secretion in a dose-dependent manner (r = −0.991, p<0.01 ). The above drugs also blocked or decreased high K+-induced secretion, but had much less effect on TRH-induced secretion. Secretion induced by TRH, hyposmolarity, or high K+ was optimal at pH 7.3-7.65 and was significantly depressed at pH 6.0 or 8.0, indicating that release of hormone induced by all 3 stimuli is due to an active cell process requiring a physiologic extracellular pH and is not produced by nonspecific cell toxicity. The data suggest hyposmolarity and high K+ may share some similarities in their mechanism of stimulating secretion, which is different from that of TRH.

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