scholarly journals Dopamine regulates spine density in striatal projection neurons in a concentration-dependent manner

2020 ◽  
Vol 134 ◽  
pp. 104666 ◽  
Author(s):  
Samuel Alberquilla ◽  
Aldo Gonzalez-Granillo ◽  
Eduardo Daniel Martín ◽  
Rosario Moratalla
Keyword(s):  
Projection Neurons ◽  
Dependent Manner ◽  
Spine Density ◽  
Concentration Dependent Manner ◽  
Striatal Projection Neurons

scholarly journals Differential Muscarinic Modulation of Synaptic Transmission in Dorsal and Ventral Regions of the Rat Nucleus Accumbens Core

2014 ◽  
pp. 135-142
Author(s):  
X. JIANG ◽  
J. J. ZHANG ◽  
M. Y. WANG ◽  
N. SUI
Keyword(s):  
Nucleus Accumbens ◽  
Acetylcholine Receptors ◽  
Muscarinic Acetylcholine Receptors ◽  
Membrane Properties ◽  
Projection Neurons ◽  
Dependent Manner ◽  
Nucleus Accumbens Core ◽  
Concentration Dependent Manner ◽  
Paired Pulse ◽  
Presynaptic Mechanisms

The nucleus accumbens (NAc) core is critical in the control of motivated behaviors. The muscarinic acetylcholine receptors (mAChRs) modulating the excitatory inputs into the NAc core have been reported to impact such behaviors. Recent studies suggest that ventral and dorsal regions of the NAc core seem to be innervated by distinct populations of glutamatergic projection neurons. To further examine mAChRs modulation of these glutamatergic inputs to the NAc core, we employed intracellular recordings in rat NAc coronal slice preparation to characterize: 1) the effects of muscarine, an mAChRs agonist, on membrane properties of the NAc core neurons; 2) depolarizing synaptic potentials (DPSP) elicited by ventral and dorsal focal electrical stimuli; and 3) paired-pulse response with paired-pulse stimulation. Here we report that the paired-pulse ratio (PPR) elicited by dorsal stimuli was greater than that elicited by ventral stimuli. Bath application of muscarine (1-30 μM) decreased both ventral and dorsal DPSP in a concentration-dependent manner, with no effect on electrophysiological properties of NAc core neurons. Muscarine at 30 μM also elicited larger depression of dorsal DPSP than ventral DPSP. Moreover, muscarine increased the PPR of both dorsal and ventral DPSP. These data indicate that the glutamatergic afferent fibers traversing the dorsal and ventral NAc are separate, and that differential decrease of distinct afferent excitatory neurotransmission onto NAc core neurons may be mediated by presynaptic mechanisms.

scholarly journals Dopamine D4 Receptor Is a Regulator of Morphine-Induced Plasticity in the Rat Dorsal Striatum

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 31
Author(s):  
Alicia Rivera ◽  
Diana Suárez-Boomgaard ◽  
Cristina Miguelez ◽  
Alejandra Valderrama-Carvajal ◽  
Jérôme Baufreton ◽  
...  
Keyword(s):  
Critical Role ◽  
Combined Treatment ◽  
Dorsal Striatum ◽  
Prolonged Treatment ◽  
Projection Neurons ◽  
Spine Density ◽  
Dopamine D4 Receptor ◽  
Striatal Projection Neurons ◽  
D4 Receptor

Long-term exposition to morphine elicits structural and synaptic plasticity in reward-related regions of the brain, playing a critical role in addiction. However, morphine-induced neuroadaptations in the dorsal striatum have been poorly studied despite its key function in drug-related habit learning. Here, we show that prolonged treatment with morphine triggered the retraction of the dendritic arbor and the loss of dendritic spines in the dorsal striatal projection neurons (MSNs). In an attempt to extend previous findings, we also explored whether the dopamine D4 receptor (D4R) could modulate striatal morphine-induced plasticity. The combined treatment of morphine with the D4R agonist PD168,077 produced an expansion of the MSNs dendritic arbors and restored dendritic spine density. At the electrophysiological level, PD168,077 in combination with morphine altered the electrical properties of the MSNs and decreased their excitability. Finally, results from the sustantia nigra showed that PD168,077 counteracted morphine-induced upregulation of μ opioid receptors (MOR) in striatonigral projections and downregulation of G protein-gated inward rectifier K+ channels (GIRK1 and GIRK2) in dopaminergic cells. The present results highlight the key function of D4R modulating morphine-induced plasticity in the dorsal striatum. Thus, D4R could represent a valuable pharmacological target for the safety use of morphine in pain management.

Na+-Gated Nonselective Cation Channel From Lobster Olfactory Projection Neurons

1998 ◽  
Vol 80 (6) ◽  
pp. 3387-3391 ◽  
Author(s):  
Aslbek B. Zhainazarov ◽  
Barry W. Ache
Keyword(s):  
Alkali Metal ◽  
Oscillatory Behavior ◽  
Cation Channel ◽  
Projection Neurons ◽  
Dependent Manner ◽  
Nonselective Cation Channel ◽  
Plateau Potentials ◽  
Concentration Dependent Manner ◽  
Olfactory Interneurons

Zhainazarov, Aslbek B. and Barry W. Ache. Na+-gated nonselective cation channel from lobster olfactory projection neurons. J. Neurophysiol. 80: 3387–3391, 1998. A nonselective cation channel specifically activated by intracellular Na+ was identified in cell-free patches taken from cultured lobster olfactory projection neurons. Na+ reversibly activates the channel in a concentration-dependent manner, with a “half-effect” Na+ concentration of 76.4 mM at −60 mV. The conductance of the channel is 32 pS. The channel is permeable to both alkali metal (Li+ > Na+ > K+ > Rb+ > Cs+) and divalent (Ca2+ > Mn2+ > Sr2+ > Mg2+ > Ba2+ > Na+) cations. The presence of a channel with the ability to generate plateau potentials suggests that the channel may potentially contribute to oscillatory behavior in these olfactory interneurons.

The Anti-Atherogenic Properties of Sesamin are Mediated via Improved Macrophage Cholesterol Efflux Through PPARγ1-LXRα and MAPK Signaling

2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro
Keyword(s):  
Cholesterol Efflux ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Mapk Signaling ◽  
Luciferase Reporter ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Macrophage Cholesterol Efflux

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.

Neutrophil Elastase Potentiates Cathepsin G-lnduced Platelet Activation

1992 ◽  
Vol 68 (05) ◽  
pp. 570-576 ◽  
Author(s):  
Mary A Selak
Keyword(s):  
Neutrophil Elastase ◽  
Cell Activation ◽  
Thromboxane A2 ◽  
Creatine Phosphate ◽  
Dense Granule ◽  
Cathepsin G ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Low Concentrations ◽  
High Concentrations

SummaryWe have previously demonstrated that human neutrophil cathepsin G is a strong platelet agonist that binds to a specific receptor. This work describes the effect of neutrophil elastase on cathepsin G-induced platelet responses. While platelets were not activated by high concentrations of neutrophil elastase by itself, elastase enhanced aggregation, secretion and calcium mobilization induced by low concentrations of cathepsin G. Platelet aggregation and secretion were potentiated in a concentration-dependent manner by neutrophil elastase with maximal responses observable at 200 nM. Enhancement was observed when elastase was preincubated with platelets for time intervals of 10–60 s prior to addition of a low concentration of cathepsin G and required catalytically-active elastase since phenylmethanesulphonyl fluoride-inhibited enzyme failed to potentiate cell activation. Neutrophil elastase potentiation of platelet responses induced by low concentrations of cathepsin G was markedly inhibited by creatine phosphate/creatine phosphokinase and/or indomethacin, indicating that the synergism between elastase and cathepsin G required the participation of ADP and thromboxane A2. On the other hand, platelet responses were not attenuated by the PAF antagonist BN 52021, signifying that PAF-acether did not play a role in elastase potentiation. At higher concentrations porcine pancreatic elastase exhibits similar effects to neutrophil elastase, demonstrating that the effect of elastase was not unique to the neutrophil protease. While neutrophil elastase failed to alter the ability of cathepsin G to hydrolyze a synthetic chromogenic substrate, preincubation of platelets with elastase increased the apparent affinity of cathepsin G binding to platelets. In contrast to their effect on cathepsin G-induced platelet responses, neither neutrophil nor pancreatic elasatse potentiated aggregation or dense granule release initiated by ADP, PAF-acether, arachidonic acid or U46619, a thromboxane A2 mimetic. Moreover, unlike its effect on cathepsin G, neutrophil elastase inhibited thrombin-induced responses. The current observations demonstrate that elastase can potentiate platelet responses mediated by low concentrations of cathepsin G, suggesting that both enzymes may function synergistically to activate platelets under conditions where neutrophil degranulation occurs.

Trimucytin: A Collagen-Like Aggregating Inducer Isolated from Trimeresurus mucrosquamatus Snake Venom

1993 ◽  
Vol 69 (03) ◽  
pp. 286-292 ◽  
Author(s):  
Che-Ming Teng ◽  
Feng-Nien Ko ◽  
Inn-Ho Tsai ◽  
Man-Ling Hung ◽  
Tur-Fu Huang
Keyword(s):  
Platelet Aggregation ◽  
Snake Venom ◽  
Inositol Phosphate ◽  
Shape Change ◽  
Platelet Activating Factor ◽  
Atp Release ◽  
Platelet Membrane ◽  
Thromboxane B2 ◽  
Dependent Manner ◽  
Concentration Dependent Manner

SummaryTrimucytin is a potent platelet aggregation inducer isolated from Trimeresurus mucrosquamatus snake venom. Similar to collagen, trimucytin has a run of (Gly-Pro-X) repeats at the N-terminal amino acids sequence. It induced platelet aggregation, ATP release and thromboxane formation in rabbit platelets in a concentration-dependent manner. The aggregation was not due to released ADP since it was not suppressed by creatine phosphate/creatine phosphokinase. It was not either due to thromboxane A2 formation because indomethacin and BW755C did not have any effect on the aggregation even thromboxane B2 formation was completely abolished by indomethacin. Platelet-activating factor (PAF) was not involved in the aggregation since a PAF antagonist, kadsurenone, did not affect. However, RGD-containing peptide triflavin inhibited the aggregation, but not the release of ATP, of platelets induced by trimucytin. Indomethacin, mepacrine, prostaglandin E1 and tetracaine inhibited the thromboxane B2 formation of platelets caused by collagen and trimucytin. Forskolin and sodium nitroprusside inhibited both platelet aggregation and ATP release, but not the shape change induced by trimucytin. In quin-2 loaded platelets, the rise of intracellular calcium concentration caused by trimucytin was decreased by 12-O-tetradecanoyl phorbol-13 acetate, imipramine, TMB-8 and indomethacin. In the absence of extracellular calcium, both collagen and trimucytin caused no thromboxane B2 formation, but still induced ATP release which was completely blocked by R 59022. Inositol phosphate formation in platelets was markedly enhanced by trimucytin and collagen. MAB1988, an antibody against platelet membrane glycoprotein Ia, inhibited trimucytinand collagen-induced platelet aggregation and ATP release. However, trimucytin did not replace the binding of 125I-labeled MAB1988 to platelets. Platelets pre-exposed to trimucytin were resistant to the second challenge with trimucytin itself or collagen. It is concluded that trimucytin may activate collagen receptors on platelet membrane, and cause aggregation and release mainly through phospholipase C-phosphoinositide pathway.

Influence of Brain Gangliosides on the Formation and Properties of Supported Lipid Bilayers for Binding Kinetics Studies

2018 ◽  
Author(s):  
Luke Jordan ◽  
Nathan Wittenberg
Keyword(s):  
Lipid Bilayers ◽  
Binding Kinetics ◽  
Supported Lipid Bilayers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Supported Lipid Bilayer ◽  
Head Groups ◽  
Lipid Diffusion ◽  
Kinetics Of ◽  
Brain Gangliosides

This is a comprehensive study of the effects of the four major brain gangliosides (GM1, GD1b, GD1a, and GT1b) on the adsorption and rupture of phospholipid vesicles on SiO2 surfaces for the formation of supported lipid bilayer (SLB) membranes. Using quartz crystal microbalance with dissipation monitoring (QCM-D) we show that gangliosides GD1a and GT1b significantly slow the SLB formation process, whereas GM1 and GD1b have smaller effects. This is likely due to the net ganglioside charge as well as the positions of acidic sugar groups on ganglioside glycan head groups. Data is included that shows calcium can accelerate the formation of ganglioside-rich SLBs. Using fluorescence recovery after photobleaching (FRAP) we also show that the presence of gangliosides significantly reduces lipid diffusion coefficients in SLBs in a concentration-dependent manner. Finally, using QCM-D and GD1a-rich SLB membranes we measure the binding kinetics of an anti-GD1a antibody that has similarities to a monoclonal antibody that is a hallmark of a variant of Guillain-Barre syndrome.

Enhancement of hydroxyl radical generation by phenols and their reaction intermediates during ozonation

1998 ◽  
Vol 38 (6) ◽  
pp. 147-154 ◽  
Author(s):  
Hideo Utsumi ◽  
Sang-Kuk Han ◽  
Kazuhiro Ichikawa
Keyword(s):  
Hydroxyl Radical ◽  
Hydroxyl Radicals ◽  
Spin Trapping ◽  
Active Species ◽  
Generation Rate ◽  
Peak Height Ratio ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Phenol Derivatives ◽  
Semiquinone Radicals

Generation of hydroxyl radicals, one of the major active species in ozonation of water was directly observed with a spin-trapping/electron spin resonance (ESR) technique using 5,5-dimethyl-1-pyrrolineN-oxide (DMPO) as a spin-trapping reagent. Hydroxyl radical were trapped with DMPO as a stable radical, DMPO-OH. Eighty μM of ozone produced 1.08 X 10-6M of DMPO-OH, indicating that 1.4% of •OH is trapped with DMPO. Generation rate of DMPO-OH was determined by ESR/stopped-flow measurement. Phenol derivatives increased the amount and generation rate of DMPO-OH, indicating that phenol derivatives enhance •OH generation during ozonation of water. Ozonation of 2,3-, 2,5-, 2,6-dichlorophenol gave an ESR spectra of triplet lines whose peak height ratio were 1:2:1. ESR parameters of the triplet lines agreed with those of the corresponding dichloro-psemiquinone radical. Ozonation of 2,4,5- and 2,4,6-trichlorophenol gave the same spectra as those of 2,5- and 2,6-dichlorophenol, respectively, indicating that a chlorine group in p-position is substituted with a hydroxy group during ozonation. Amounts of the radical increased in an ozone-concentration dependent manner and were inhibited by addition of hydroxyl radical scavengers. These results suggest that p-semiquinone radicals are generated from the chlorophenols by hydroxyl radicals during ozonation. The p-semiquinone radicals were at least partly responsible for enhancements of DMPO-OH generation.

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