Influence of salidroside, a neuroactive compound of Rhodiola rosea L., on alcohol tolerance development in rats

SummaryIntroduction: In recent years, the search for potential neuroprotective properties of salidroside and its ability to influence the activity of nervous system become the subject of intense studies of many research groups. None of these studies, however, include an attempt to determine the effect of salidroside on the course of alcohol tolerancein vivo.Objective: The aim of this study was to investigate the ability of salidroside to inhibit the development of alcohol tolerance in rats, determining whether the effect of its action may occur in a dose-dependent manner, reducing both metabolic and central tolerance without affecting body temperature in control rats.Methods: Male Wistar rats were injected daily with ethanol at a dose of 3 g/kg for 9 consecutive days to produce ethanol tolerance. Salidroside in two doses (4.5 mg/kg and 45 mg/kgb.w.) orvehiculumwas administered orally. On the 1st, 3rd, 5th and 8th day a hypothermic effect of ethanol was measured, while the loss of righting reflex procedure was performed on the 2nd, 4th, 6th and 7th day. On the 9th day rats were treated with salidroside, sacrificed 1 h after ethanol injections and blood was collected for blood-ethanol concentration measurement.Results: Salidroside at a dose of 45 mg/kg inhibited the development of tolerance to hypothermic and sedative effects of ethanol, whereas insignificant elevation of blood-ethanol concentration was observed. The dose of 4.5 mg/kgb.w.had minimal effect, only small inhibition of tolerance to hypothermic action was observed. Salidroside affected neither body mass growth nor body temperature in non-alcoholic (control) rats.Conclusions: Results of the study indicate that salidroside at a dose of 45 mg/kg inhibited the development of tolerance to the hypothermic effect of ethanol. Observed inhibition of tolerance to the sedative effect of ethanol seems to be associated with salidroside influence on the central nervous system. A comprehensive explanation of the abovementioned observations requires further pharmacological and pharmacodynamic studies.

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Influence of extracts from Rhodiola rosea and Rhodiola kirilowii on the development of alcohol tolerance in rats

Herba Polonica ◽

10.2478/hepo-2018-0021 ◽

2018 ◽

Vol 64 (4) ◽

pp. 34-43

Author(s):

Michał Szulc ◽

Piotr Mularczyk ◽

Patryk Grządzielski ◽

Przemysław Zakowicz ◽

Radosław Kujawski ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Rhodiola Rosea ◽

Alcohol Tolerance ◽

Ethanol Injection ◽

Loss Of Righting Reflex ◽

Male Wistar Rats ◽

The Central Nervous System ◽

Development Of Tolerance

Summary Introduction: Rhodiola rosea (RR) and Rhodiola kirilowii (RK) are well known for their influence on central nervous system, however their impact on the development of alcohol tolerance has not yet been proven. Objective: The aim of this study was to determine the ability of RR and RK roots extracts to inhibit the development of alcohol tolerance in vivo, both, peripheral (metabolic) and central ones. Methods: Male Wistar rats were treated with RR and RK extracts (p.o.) and ethanol (i.p.) for ten consecutive days. On the first, third, fifth and eighth days the hypothermic action of ethanol was measured, while on the ninth day the loss of righting reflex was examined. On the tenth day rats were treated with assigned extract and sacrificed 1 h after the ethanol injection. Results: Both extracts inhibited development of tolerance to the hypothermic action of ethanol. The observed effect seems to be specific since none of the extracts affected body temperature in water-treated animals. RK extract also prolonged the hypnotic action of ethanol. RR-treated rats had higher blood-ethanol concentrations, in contrast to RK ones. Conclusions: RR and RK extracts inhibited the development of tolerance to the hypothermic action of ethanol. Prolongation of the hypnotic action of ethanol by RK extract may be associated with influence on the central nervous system, while the RR one also inhibited the development of metabolic tolerance.

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Neurons Are Host Cells for Mycobacterium tuberculosis

Infection and Immunity ◽

10.1128/iai.00474-13 ◽

2014 ◽

Vol 82 (5) ◽

pp. 1880-1890 ◽

Cited By ~ 6

Author(s):

Philippa J. Randall ◽

Nai-Jen Hsu ◽

Dirk Lang ◽

Susan Cooper ◽

Boipelo Sebesho ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Mycobacterium Tuberculosis ◽

Host Cells ◽

Productive Infection ◽

Target Cells ◽

Dependent Manner ◽

Content Type ◽

The Central Nervous System

ABSTRACTMycobacterium tuberculosisinfection of the central nervous system is thought to be initiated once the bacilli have breached the blood brain barrier and are phagocytosed, primarily by microglial cells. In this study, the interactions ofM. tuberculosiswith neuronsin vitroandin vivowere investigated. The data obtained demonstrate that neurons can act as host cells forM. tuberculosis.M. tuberculosisbacilli were internalized by murine neuronal cultured cells in a time-dependent manner after exposure, with superior uptake by HT22 cells compared to Neuro-2a cells (17.7% versus 9.8%). Internalization ofM. tuberculosisbacilli by human SK-N-SH cultured neurons suggested the clinical relevance of the findings. Moreover, primary murine hippocampus-derived neuronal cultures could similarly internalizeM. tuberculosis. InternalizedM. tuberculosisbacilli represented a productive infection with retention of bacterial viability and replicative potential, increasing 2- to 4-fold within 48 h.M. tuberculosisbacillus infection of neurons was confirmedin vivoin the brains of C57BL/6 mice after intracerebral challenge. This study, therefore, demonstrates neurons as potential new target cells forM. tuberculosiswithin the central nervous system.

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Mitochondrial Calcium Uptake Capacity Modulates Neocortical Excitability

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2013.61 ◽

2013 ◽

Vol 33 (7) ◽

pp. 1115-1126 ◽

Cited By ~ 23

Author(s):

Basavaraju G Sanganahalli ◽

Peter Herman ◽

Fahmeed Hyder ◽

Sridhar S Kannurpatti

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Cell Types ◽

Dependent Manner ◽

Evoked Responses ◽

Blood Oxygen Level ◽

Calcium Uniporter ◽

Sensory Evoked

Local calcium (Ca2 +) changes regulate central nervous system metabolism and communication integrated by subcellular processes including mitochondrial Ca2 + uptake. Mitochondria take up Ca2 + through the calcium uniporter (mCU) aided by cytoplasmic microdomains of high Ca2 +. Known only in vitro, the in vivo impact of mCU activity may reveal Ca2 + -mediated roles of mitochondria in brain signaling and metabolism. From in vitro studies of mitochondrial Ca2 + sequestration and cycling in various cell types of the central nervous system, we evaluated ranges of spontaneous and activity-induced Ca2 + distributions in multiple subcellular compartments in vivo. We hypothesized that inhibiting (or enhancing) mCU activity would attenuate (or augment) cortical neuronal activity as well as activity-induced hemodynamic responses in an overall cytoplasmic and mitochondrial Ca2 + -dependent manner. Spontaneous and sensory-evoked cortical activities were measured by extracellular electrophysiology complemented with dynamic mapping of blood oxygen level dependence and cerebral blood flow. Calcium uniporter activity was inhibited and enhanced pharmacologically, and its impact on the multimodal measures were analyzed in an integrated manner. Ru360, an mCU inhibitor, reduced all stimulus-evoked responses, whereas Kaempferol, an mCU enhancer, augmented all evoked responses. Collectively, the results confirm aforementioned hypotheses and support the Ca2 + uptake-mediated integrative role of in vivo mitochondria on neocortical activity.

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Comparison of the Effects of Convulsant and Depressant Barbiturate Stereoisomers on AMPA-type Glutamate Receptors

Anesthesiology ◽

10.1097/00000542-199906000-00028 ◽

1999 ◽

Vol 90 (6) ◽

pp. 1704-1713. ◽

Cited By ~ 23

Author(s):

Yoshinori Kamiya ◽

Tomio Andoh ◽

Ryosuke Furuya ◽

Satoshi Hattori ◽

Itaru Watanabe ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Glutamate Receptors ◽

Ampa Receptor ◽

Ampa Receptors ◽

Dependent Manner ◽

Induced Current ◽

Gaba A ◽

The Central Nervous System

Background Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system. Although barbiturates have been shown to suppress the AMPA receptor-mediated responses, it is unclear whether this effect contributes to the anesthetic action of barbiturates. The authors compared the effects of depressant [R(-)] and convulsant [S(+)] stereoisomers of 1-methyl-5-phenyl-5-propyl barbituric acid (MPPB) on the AMPA and gamma-aminobutyric acid type A (GABA(A)) receptor-mediated currents to determine if the inhibitory effects on AMPA receptors correlate to the in vivo effects of the isomers. Method The authors measured whole-cell currents in the rat cultured cortical neuron at holding potential of -60 mV. Kainate 500 microM was applied as the agonist for AMPA receptors. Thiopental (3-300 microM), R(-)-MPPB or S(+)-MPPB (100-1,000 microM) was coapplied with kainate under the condition in which the GABA(A) receptor-mediated current was blocked. Effects of MPPB isomers on the current elicited by GABA 1 microM were studied in the separate experiments. Results Thiopental inhibited the kainate-induced current reversibly and in a dose-dependent manner, with a concentration for 50% inhibition of 49.3 microM. Both R(-)-MPPB and S(+)-MPPB inhibited the kainate-induced current with a little stereoselectivity. R(-)-MPPB was slightly but significantly more potent than S(+)-MPPB. In contrast, R(-)-MPPB enhanced but S(+)-MPPB reduced the GABA-induced current. Conclusions Both convulsant and depressant stereoisomers of the barbiturate inhibited the AMPA receptor-mediated current despite of their opposite effects on the central nervous system in vivo. Although thiopental exhibited a considerable inhibition of AMPA receptors, the results suggest that the inhibition of AMPA receptors contributes little to the hypnotic action of the barbiturates.

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Cannabinoid CB2 receptors in the enteric nervous system modulate gastrointestinal contractility in lipopolysaccharide-treated rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.90285.2008 ◽

2008 ◽

Vol 295 (1) ◽

pp. G78-G87 ◽

Cited By ~ 81

Author(s):

Marnie Duncan ◽

Abdeslam Mouihate ◽

Ken Mackie ◽

Catherine M. Keenan ◽

Nancy E. Buckley ◽

...

Keyword(s):

Nervous System ◽

Enteric Nervous System ◽

Myenteric Plexus ◽

Electrical Field Stimulation ◽

Receptor Expression ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Receptor Agonists ◽

Lps Treatment

Enhanced intestinal transit due to lipopolysaccharide (LPS) is reversed by cannabinoid (CB)2 receptor agonists in vivo, but the site and mechanism of action are unknown. We have tested the hypothesis that CB2 receptors are expressed in the enteric nervous system and are activated in pathophysiological conditions. Tissues from either saline- or LPS-treated (2 h; 65 μg/kg ip) rats were processed for RT-PCR, Western blotting, and immunohistochemistry or were mounted in organ baths where electrical field stimulation was applied in the presence or absence of CB receptor agonists. Whereas the CB2 receptor agonist JWH133 did not affect the electrically evoked twitch response of the ileum under basal conditions, in the LPS-treated tissues JWH133 was able to reduce the enhanced contractile response in a concentration-dependent manner. Rat ileum expressed CB2 receptor mRNA and protein under physiological conditions, and this expression was not affected by LPS treatment. In the myenteric plexus, CB2 receptors were expressed on the majority of neurons, although not on those expressing nitric oxide synthase. LPS did not alter the distribution of CB2 receptor expression in the myenteric plexus. In vivo LPS treatment significantly increased Fos expression in both enteric glia and neurons. This enhanced expression was significantly attenuated by JWH133, whose action was reversed by the CB2 receptor antagonist AM630. Taking these facts together, we conclude that activation of CB2 receptors in the enteric nervous system of the gastrointestinal tract dampens endotoxin-induced enhanced intestinal contractility.

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Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways

10.1101/2020.06.09.142133 ◽

2020 ◽

Author(s):

Lihua Ye ◽

Munhyung Bae ◽

Chelsi D. Cassilly ◽

Sairam V. Jabba ◽

Daniel W. Thorpe ◽

...

Keyword(s):

Nervous System ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Enteroendocrine Cells ◽

Enteric Neurons ◽

Edwardsiella Tarda ◽

Dependent Manner ◽

Tryptophan Catabolism ◽

Transient Receptor

SUMMARYThe intestinal epithelium senses nutritional and microbial stimuli using epithelial sensory enteroendocrine cells (EECs). EECs can communicate nutritional information to the nervous system, but similar mechanisms for microbial information are unknown. Using in vivo real-time measurements of EEC and nervous system activity in zebrafish, we discovered that the bacteria Edwardsiella tarda specifically activates EECs through the receptor transient receptor potential ankyrin A1 (Trpa1) and increases intestinal motility in an EEC-dependent manner. Microbial, pharmacological, or optogenetic activation of Trpa1+EECs directly stimulates vagal sensory ganglia and activates cholinergic enteric neurons through 5-HT. We identified a subset of indole derivatives of tryptophan catabolism produced by E. tarda and other gut microbes that potently activates zebrafish EEC Trpa1 signaling and also directly stimulates human and mouse Trpa1 and intestinal 5-HT secretion. These results establish a molecular pathway by which EECs regulate enteric and vagal neuronal pathways in response to specific microbial signals.

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VASODILATOR PEPTIDES - CGRP AND VIP

10.1055/s-0038-1643720 ◽

1987 ◽

Author(s):

S Thom ◽

A Hughes ◽

G Martin ◽

P Goldberg ◽

P Server

Keyword(s):

Blood Flow ◽

Nervous System ◽

Cerebral Arteries ◽

Venous Occlusion ◽

Dependent Manner ◽

Pial Arteries ◽

Parasympathetic System ◽

Perivascular Nerves

The two peptides calcitonin gene related peptide (C6RP) and vasoactive intestinalpeptide (VIP) are widely distributed in animal species including man and a number ofdiverse actions of the peptides have been described [1,2]. They share vasoactive properties [3,4] and may have important functions as neurotransmitters in a non-adrenergic, non-cholinergic nervous system [5]. VIP has been located in perivascular nerves supplying several tissues and is co-stored with acetylcholine in the parasympathetic system [6]. CGRP has also been widely identified in the nervous system, the cardiovascular system and perivascular nerves, where it is located with substance P[7]. Our studies have assessed the activity of these peptides in a human vascular resistance bed -the forearm, and on isolated human blood vessels.Forearm studies were performed by infusingCGRP (10,30,100 ng/min) or ViP (10,30,100 ng/min) via the brachial artery for 5 min at each dose level and measuring blood flow by venous occlusion plethysmography. In vitro studies were performed using ringsegments of pulmonary, gastric, coronary, radial, and transverse cervical arteries freshly obtained from surgical resection specimens and cerebral arteries obtained from autogsy tissue within 4 hours of death. Vessels were mounted in organ baths containing Krebs buffer aerated with 95% 02, 5% C02 at 37C, and preconstricted using a submaximal concentration of noradrenaline (1-3 μM) or prostaglandin F2a (I-IO11μ7.CGRP or VIP was added to the tissue bath in a cumulative fashion. All arterial segments used for these studies relaxed in response to acetylcholine (0.1-3μM)or A23187 (0.1-3μM) and this was regarded as indicative of functional endothelial integrity. Studies were performed in the presence of indomethacin (lOμM). The endothelium was deliberately removed from some rings and in others haemoglobin (5μM) ormethylene blue (lOμM) were added to the tissue bath after the arterialrings were effectively relaxed by CGRP orVIP. Both peptides produced marked dose dependent increases in forearm blood flow; at 100 ng/min the mean net increase was 174 ± 24% (mean ±s.e.m.) with CGRP, and 223 + 34% (mean +s.e.m.) with VIP. In vitro CGRP (InM-lμM) relaxed preconstricted segments ofradial Tn=2), coronary (n=4), gastric (n=5) and cerebral (n=3) arteries in an endothelium dependent manner. VIP (1 nM - 1pm) also relaxed human gastric (n=2), splenic (n=2), cervical (n=3) and pulmonary (n=5) arteries VIP relaxation of the gastric and cervical arteries was dependent on the presence of endothelium; however, VIP inducedrelaxation of pulmonary artery was not dependent on functional endothelium. The endothelium dependent relaxations could be abolished either by luminal rubbing, additionor haemoglobin or methylene blue. Together these results might be taken to imply that the forearm vasodilatation response is mediated by EDRF. However, caution is necessary in extrapolating from in vitro observations of large vessels to the in vivo response of a resistance vascular bed.Others have demonstrated that the CGRPand VIP relaxatory responses of smaller human pial arteries (ID 250-600 pm) are endothelium independent [8] and preliminary work in our department supports this. The EDRF mechanism is cyclic GMP linked, but most of the studied functions of VIP and CGRP seem to be linked to a rise in cyclic AMP-. A further paradox is that the blood flow response to infused acetylcholine, the archetypal releaser of EDRF, is evanescent, and yet the vasodilator response to CGRP is persistent.

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Evaluation of central nervous system depressant activity of methanolic and petroleum ether extract of Manilkara zapota leaves (in vivo)

International Journal of Phytomedicine ◽

10.5138/09750185.1896 ◽

2016 ◽

Vol 8 (3) ◽

pp. 308

Author(s):

Manirujjaman ◽

Trudi Collet

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Locomotor Activity ◽

Petroleum Ether ◽

Open Field ◽

Dependent Manner ◽

Manilkara Zapota ◽

Cns Depressant ◽

Cns Depressant Activity

The purpose of this study was to examine the central nervous system (CNS) -depressant activity of methanolic and petroleum ether extracts of leaves obtained from Manilkara zapota (Sapotaceae) in vivo. CNS-depressant action was evaluated by observing the effects of plant extracts on both exploratory and spontaneous locomotor activity in mice using open field and hole cross tests respectively. The extracts were found to exhibit CNS-depressant activity in a dose-dependent manner. In the open field test, both the methanolic and petroleum ether extracts reduced the exploratory behavior of mice significantly (p<0.05). Although the extracts reduced locomotor activity in the hole cross test, the results were found to be insignificant. Overall, these findings indicate that both types of extracts derived from M. zapota leaves possess CNS-depressant activity.

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The Impact of α-Adrenoceptors in the Regulation of the Hypotonicity-Induced Increase in Duodenal Mucosal Permeability In Vivo

Pharmaceutics ◽

10.3390/pharmaceutics13122096 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2096

Author(s):

John Sedin ◽

David Dahlgren ◽

Markus Sjöblom ◽

Olof Nylander

Keyword(s):

Blood Pressure ◽

Nervous System ◽

Sympathetic Nervous System ◽

Arterial Blood Pressure ◽

Dependent Manner ◽

Mucosal Permeability ◽

Arterial Blood ◽

Α2 Adrenoceptor ◽

Sympathetic Nervous

The duodenal mucosa is regularly exposed to a low osmolality, and recent experiments suggest that hypotonicity increases mucosal permeability in an osmolality-dependent manner. The aim was to examine whether the sympathetic nervous system, via action on α-adrenoceptors, affects the hypotonicity-induced increase in duodenal mucosal permeability. The duodenum of anaesthetised rats was perfused in vivo with a 50 mM NaCl solution in the presence of adrenergic α-adrenoceptor drugs. Studied were the effects on mucosal permeability (blood-to-lumen clearance of 51Cr-EDTA), arterial blood pressure, luminal alkalinisation, transepithelial fluid flux, and motility. Hypotonicity induced a six-fold increase in mucosal permeability, a response that was reversible and repeatable. The α2-adrenoceptor agonist clonidine abolished the hypotonicity-induced increase in mucosal permeability, reduced arterial blood pressure, inhibited duodenal motility, and decreased luminal alkalinisation. The α2-adrenoceptor antagonists, yohimbine and idazoxan, prevented the inhibitory effect of clonidine on the hypotonicity-induced increase in mucosal permeability. The α1-agonist phenylephrine or the α1-antagonist prazosin elicited their predicted effect on blood pressure but did not affect the hypotonicity-induced increase in mucosal permeability. None of the α1- or α2-adrenoceptor drugs changed the hypotonicity-induced net fluid absorption. In conclusion, stimulation of the adrenergic α2-adrenoceptor prevents the hypotonicity-induced increase in mucosal permeability, suggesting that the sympathetic nervous system has the capability to regulate duodenal mucosal permeability.

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