bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of medullary A2 noradrenergic neurons in the activation of oxytocin neurons after conditioned fear stimuli
Authors: Zhu Lingling , Onaka Tatsushi 
Published: March 2003

AbstractFear‐related stimuli activate oxytocin neurons in the hypothalamus and facilitate oxytocin release from the pituitary. Oxytocin neurons in the supraoptic nucleus receive direct noradrenergic innervations from the A1 and A2 cell groups in the medulla oblongata. In the present study, we investigated the role of hypothalamic‐projecting noradrenergic neurons in controlling oxytocin cell activity following fear‐related stimuli in rats. An unconditioned fear stimulus (intermittently applied footshock) or conditioned fear stimulus induced expression of Fos protein, a protein product of an immediate‐early gene, in magnocellular oxytocin neurons in the supraoptic or paraventricular nucleus. A neurotoxin, 5‐amino‐2,4‐dihydroxy‐α‐methylphenylethylamine, microinjected into the vicinity of the supraoptic nucleus, selectively depleted the noradrenaline contents of the nucleus and blocked the Fos expression in the supraoptic nucleus after the unconditioned or conditioned fear stimulus. In the medulla oblongata, the unconditioned fear stimulus induced expression of Fos protein in both A2/C2 and A1/C1 catecholaminergic neurons. On the other hand, the conditioned fear stimulus induced expression of Fos protein preferentially in the A2/C2 neurons. Furthermore, the unconditioned fear stimulus induced Fos expression in the A1/C1 and A2/C2 catecholaminergic neurons labelled with retrograde tracers previously injected into the supraoptic nucleus. The conditioned fear stimulus induced Fos expression preferentially in the A2/C2 catecholaminergic neurons labelled with the retrograde tracers. These data suggest that the conditioned fear‐induced oxytocin cell activity is mediated by the A2 noradrenergic neurons projecting to oxytocin neurons, while the unconditioned fear response is mediated by both A2 and A1 noradrenergic neurons.
Developmental event‐related gamma oscillations: effects of auditory attention
Authors: Yordanova Juliana , Kolev Vasil , Heinrich Hartmut , Woerner Wolfgang , Banaschewski Tobias , Rothenberger Aribert 
Published: March 2003

AbstractThis study describes maturational changes in topographical patterns, stability, and functional reactivity of auditory gamma band (31–63 Hz) responses (GBRs) as brain electrical correlates relevant for cognitive development during childhood. GBRs of 114 healthy children from 9 to 16 years were elicited in an auditory focused attention task requiring motor responding to targets, and analyzed by means of the wavelet transform (WT). The effects of age and task variables (attended side and stimulus type relevance) were examined for GBR power and phase‐locking within 120 ms after stimulation. Similar to the spontaneous gamma band power, the power and phase‐synchronization of GBRs did not depend on the age. However, the functional reactivity of GBRs at specific locations changed in the course of development. In 9–12‐year‐old children, GBRs at frontal locations were larger and better synchronized to target than to nontarget stimulus type, and were larger over the left hemisphere (contralateral to the responding hand), thus manifesting sensitivity to external stimulus features and motor task. In 13–16‐year‐old adolescents, GBRs at parietal sites were enhanced by active attending to the side of stimulation, thus being associated with a maintenance of attentional focus to stimulus location. The results indicate that (i) specific aspects of task‐stimulus processing engage distinct spatially localized gamma networks at functionally relevant areas, and (ii) the neuronal substrates of gamma band networks and the ability to synchronize them in relation to task‐specific processes are available in all age groups from 9 to 16 years. However, the mode and efficiency with which gamma networks can be entrained depends on the age. This age‐dependent reactivity of GBRs to different task variables may reflect a transition in processing strategies emerging at approximately 12–13 years in relation to the maturation of cognitive and executive brain functions.
Interferon‐γ differentially modulates the release of cytokines and chemokines in lipopolysaccharide‐ and pneumococcal cell wall‐stimulated mouse microglia and macrophages
Authors: Häusler Karl Georg , Prinz Marco , Nolte Christiane , Weber Joerg R. , Schumann Ralf R. , Kettenmann Helmut , Hanisch Uwe‐Karsten 
Published: March 2003

AbstractDuring bacterial infections of the CNS, activated microglia could support leucocyte recruitment to the brain through the synthesis of cyto‐ and chemokines. In turn, invading leucocytes may feedback on microglial cells to influence their chemokine release pattern. Here, we analyzed the capacity of interferon‐γ (IFNγ) to serve as such a leucocyte‐to‐microglia signal. Production of cyto‐ and chemokines was stimulated in mouse microglia cultures by treatments with lipopolysaccharide (LPS) from Gram‐negative Escherichia coli or cell walls from Gram‐positive Streptococcus pneumoniae (PCW). IFNγ presence during the stimulation (0.1–100 ng/mL) modulated the patterns of LPS‐ and PCW‐induced cyto‐ and chemokine release in a dose‐dependent, potent and complex manner. While amounts of TNFα and IL‐6 remained nearly unchanged, IFNγ enhanced the production of IL‐12, MCP‐1 and RANTES, but attenuated that of KC, MIP‐1α and MIP‐2. Release modulation was obtained with IFNγ preincubation (treatment of cells before LPS or PCW administration), coincubation and even delayed addition to an ongoing LPS or PCW stimulation. Together the changes observed for the microglial chemokine release under IFNγ would shift the chemoattractive profile from favouring neutrophils to a preferential attraction of monocytes and T lymphocyte populations – as actually seen during the course of bacterial meningitis. The findings support the view of activated microglia as a major intrinsic source for an instant production of a variety of chemokines and suggest that leucocyte‐derived IFNγ could potentially regulate the microglial chemokine release pattern.
Effects of polyunsaturated fatty acids on voltage‐gated K+ and Na+ channels in rat olfactory receptor neurons
Authors: Seebungkert Benchamaporn , Lynch Joseph W. 
Published: March 2003

AbstractAlthough the polyunsaturated fatty acids arachidonic acid (AA) and docosahexaenoic acid (DHA) are enriched in the olfactory mucosa, their possible contribution to olfactory transduction has not been investigated. This study characterized their effects on voltage‐gated K+ and Na+ channels of rat olfactory receptor neurons. Physiological (3–10 µm) concentrations of AA and DHA potently and irreversibly inhibited the voltage‐gated K+ current in a voltage‐independent manner. In addition, both compounds significantly reduced the inhibitory potency of the odorants acetophenone and amyl acetate at these channels. By comparison, the steady‐state effects of both AA and DHA on the voltage‐gated Na+ channel were relatively weak, with half‐maximal inhibition requiring ≈ 35 µm of either compound. However, a surprising finding was that the initial application of 3 µm AA to a naïve neuron caused a strong but transient inhibition of the Na+ current. The channels became almost completely resistant to this inhibition within 1 min, and a 2‐min wash in control solution was insufficient to restore the strong inhibitory effect. These observations suggest that polyunsaturated fatty acids have the potential to strongly influence the coding of odorant information by olfactory receptor neurons.
Cholinergic modulation of nucleus accumbens medium spiny neurons
Authors: De Rover Mischa , Lodder Johannes C. , Kits Karel S. , Schoffelmeer Anton N. M. , Brussaard Arjen B. 
Published: March 2003

AbstractThe rat nucleus accumbens contains acetylcholine‐releasing interneurons, presumed to play a regulatory role in the electrical activity of medium spiny output neurons. In order to examine this issue in detail, we made electrophysiological recordings in rat nucleus accumbens slices. These experiments showed that γ‐aminobutyric acid‐mediated inhibition of the output neurons might be facilitated by activation of nicotinic acetylcholine receptors, in addition to being suppressed via activation of muscarinic acetylcholine receptors. In contrast, glutamatergic excitation of output neurons appeared to be inhibited by activation of muscarinic acetylcholine receptors and to be insensitive to activation of nicotinic acetylcholine receptors. The spontaneous firing frequency of cholinergic neurons appeared to be under control of both a muscarinic and a nicotinic pathway in a bi‐directional manner. Finally, we made paired recordings in which the functional connection between cholinergic neurons and output neurons was monitored. Driving the cholinergic neurons at physiological firing frequencies stimulated γ‐aminobutyric acid‐mediated inhibition of the output neurons, via activation of nicotinic acetylcholine receptors. The onset of this effect was slow and lacked a fixed delay. These data indicate that activation of nicotinic acetylcholine receptors in rat nucleus accumbens may mediate the facilitation of γ‐aminobutyric acid‐mediated inhibition of medium spiny output neurons. Possible mechanisms of neurotransmission, mediating this cholinergic modulation are discussed.
Silymarin protects dopaminergic neurons against lipopolysaccharide‐induced neurotoxicity by inhibiting microglia activation
Authors: Wang Mei‐Jen , Lin Wan‐Wan , Chen Huan‐Lian , Chang Ying‐Hsin , Ou Hsio‐Chung , Kuo Jon‐Son , Hong Jau‐Shyong , Jeng Kee‐Ching G. 
Published: March 2003

AbstractAn inflammatory response in the central nervous system mediated by activation of microglia is a key event in the early stages of the development of neurodegenerative diseases. Silymarin is a polyphenolic flavanoid derived from milk thistle that has anti‐inflammatory, cytoprotective and anticarcinogenic effects. In this study, we first investigated the neuroprotective effect of silymarin against lipopolysaccharide (LPS)‐induced neurotoxicity in mesencephalic mixed neuron–glia cultures. The results showed that silymarin significantly inhibited the LPS‐induced activation of microglia and the production of inflammatory mediators, such as tumour necrosis factor‐α and nitric oxide (NO), and reduced the damage to dopaminergic neurons. Therefore, the inhibitory mechanisms of silymarin on microglia activation were studied further. The production of inducible nitric oxide synthase (iNOS) was studied in LPS‐stimulated BV‐2 cells as a model of microglia activation. Silymarin significantly reduced the LPS‐induced nitrite, iNOS mRNA and protein levels in a dose‐dependent manner. Moreover, LPS could induce the activation of p38 mitogen‐activated protein kinase (MAPK) and c‐jun N‐terminal kinase but not extracellular signal‐regulated kinase. The LPS‐induced production of NO was inhibited by the selective p38 MAPK inhibitor SB203580. These results indicated that the p38 MAPK signalling pathway was involved in the LPS‐induced NO production. However, the activation of p38 MAPK was not inhibited by silymarin. Nevertheless, silymarin could effectively reduce LPS‐induced superoxide generation and nuclear factor kappaB (NF‐κB) activation. It suggests that the inhibitory effect of silymarin on microglia activation is mediated through the inhibition of NF‐κB activation.
Activity‐dependent modulation of GABAergic synapses in developing rat spinal networks in vitro
Authors: Rosato‐Siri Marcelo , Grandolfo Micaela , Ballerini Laura 
Published: March 2003

AbstractThe role of activity‐dependent plasticity in modulating inhibitory synapses was investigated in embryonic rat spinal cord slice cultures, by chronic exposure to non‐NMDA receptor blockers. GABAergic synaptic efficacy in control and chronic‐treated cultures was investigated by patch‐recordings from visually identified spinal interneurons. In both culture groups proximal stimulation induced the appearance of postsynaptic currents (PSCs), which were fully antagonized by 20 µM bicuculline application and reverse polarity at potential values close to those reported for spontaneous GABAergic PSCs. In chronically treated cells GABAergic evoked PSCs displayed a larger failure rate and a smaller coefficient of variation of mean PSC amplitude, when compared to controls. As opposed to controls, chronic GABAergic evoked PSCs did not facilitate upon paired‐pulse stimulation. Facilitation at chronic synapses was observed when extracellular calcium levels were decreased below physiological values (< 2 mM). Kainate was used to disclose any functional differences between control and treated slices. In accordance with the presynaptic action of kainate, the application of this drug along with GYKI, an AMPA receptor selective antagonist, changed, with analogous potency, short‐term plasticity of GABAergic synapses from control and treated cultures. Nevertheless, in chronic cultures, the downstream effects of such activation unmasked short‐term depression. Ultrastructural analysis of synapses in chronically treated cultures showed a reduction both in symmetric synapses and in the number of vesicles at symmetric terminals. Thus, based on electrophysiological and ultrastructural data, it could be suggested that during the development of spinal circuits, GABAergic synapses are modulated by glutamatergic transmission, and thus implying that excitatory transmission regulates the strength of GABAergic synapses.
Substance P mobilizes intracellular calcium and activates a nonselective cation conductance in rat spiral ganglion neurons
Authors: Ito Ken , Rome Claire , Bouleau Yohan , Dulon Didier 
Published: March 2003

AbstractWe demonstrate the expression of functional tachykinin receptors in rat spiral ganglion neurons (SGNs) using calcium signal measurement and whole‐cell patch clamp recording. Substance P (SP; 10 µm, 1 s application) induced a transient increase in intracellular calcium. The SP dose–response study showed an EC50 of 18.8 µm and a Hill slope of 0.77. Comparison between specific agonists for the three tachykinin receptor (NKR) types showed the potency NKR3 > NKR1 > NKR2 at 10 µm. The Ca2+ response could be evoked in Ca2+‐free medium and was blocked by N‐ethylmaleimide and U‐73122, indicating that Ca2+ was released from intracellular stores via a G‐protein and phospholipase C pathway. Under whole‐cell voltage clamp recording at a holding potential of −50 mV, SP (10 µm, 1 s) evoked a slowly developing transient inward current. The current reversed near to 0 mV and ionic permeability experiments revealed a cation nonselective conductance also permeable to large organic cations such as N‐methyl‐d‐glucamine and tetraethylammonium. Neither removing extracellular calcium nor chelating intracellular calcium with 10 mm BAPTA could block the SP‐evoked current. This conductance appeared coupled to G‐protein activation as intracellular GDP‐βS blocked the SP‐evoked current. Mutual desensitization and occlusion studies with acetylcholine and ATP showed that the SP‐evoked conductance share effector channels and/or intracellular processes with the purinergic/cholinergic conductance. In SGNs, SP could have both a trophic action, via a calcium response, and a neuromodulatory role, by a depolarizing action through the activation of nonselective cation channels.
Chemoreceptor activity is normal in mice lacking the NK1 receptor
Authors: Rigual Ricardo , Rico Alberto J. , Prieto‐Lloret Jesus , De Felipe Carmen , González Constancio , Donnelly David F. 
Published: March 2003

AbstractSubstance P has been proposed to be an important neurotransmitter in the carotid body with the neurokinin 1 (NK1) receptor, mediating excitation between the glomus cells and afferent nerve endings. In order to better understand the role of substance P, this study examined chemoreceptor afferent activity, in vitro, and tissue catecholamine levels and release in adult, wild‐type mice and mice lacking the gene for the NK1 receptor (NK1‐KO). Groups did not differ significantly in body weight, carotid body dopamine content or carotid body norepinephrine content. In wild‐type mice, single unit activity increased from 0.59 ± 0.14 Hz to 19.78 ± 2.27 Hz during superfusion with strong hypoxia (PO2 ≈ 25 Torr). Chemoreceptor activity in NK1‐KO mice, increased from 0.71 ± 0.23 to 21.50 ± 3.62 Hz, and neither baseline or peak frequencies were significantly different from the wild‐type group. Less severe hypoxia (PO2≈ 45 torr), evoked peak activities of 12.50 ± 1.88 and 10.64 ± 3.72 Hz in wild‐type and NK1‐KO mice, which were also not significantly different. In response to severe hypoxia, free‐tissue catecholamine increased to 4.92 ± 0.85 µm in wild‐type mice and 4.26 ± 0.63 µm in NK1‐KO mice, which were also not significantly different. It may therefore be concluded that loss of NK1 receptors has little effect on chemoreceptor function in the mouse, and thus they play, at best, a minor role in the hypoxic chemoreception process.
Reduced stress‐induced hyperthermia in mGluR5 knockout mice
Authors: Brodkin J. , Bradbury M. , Busse C. , Warren N. , Bristow L. J. , Varney M. A. 
Published: March 2003

AbstractIt hs been suggested that metabotropic glutamate receptor subtype 5 (mGluR5) play a role in the expression of anxiety, based on anxiolytic‐like effects of the selective mGluR5 antagonist MPEP (2‐methyl‐6‐(phenylethynyl)pyridine) in rodent models of anxiety, including stress‐induced hyperthermia (SIH). To examine the suggested role of mGlu5 receptors in the expression of anxiety, we examined the stress response in mice lacking mGluR5 in several variations of the SIH procedure. In this paradigm, stress causes a mild increase in body temperature that can be blocked by known anxiolytic agents. Three procedures were employed: classical SIH using rectal‐probe measurement of body temperature, and radiotelemetric measurement of body temperature in response to either saline injection or to the introduction of an intruder into the home cage. In all three procedures the mGluR5‐knockout mice displayed a significant attenuation of the hyperthermic response to stress compared to littermate wild‐type control mice. To confirm that our observations were likely to be due to the absence of mGluR5 in the knockout mice we also tested the effect of the recently described selective mGluR5 antagonist MTEP (3‐[(2‐methyl‐1,3‐thiazol‐4‐yl)ethynyl]pyridine) in both the wild‐type and mGluR5 knockout mice. Administration of MTEP in the wild‐type mice, but not the mGluR5 knockout mice, attenuated SIH. That the mGluR5 knockout mice displayed an anxiolytic‐like phenotype and that the mGluR5 antagonist, MTEP, showed a anxiolytic‐like effect only in mice possessing mGluR5 further supports the suggestion that mGluR5 antagonists may be useful in the treatment of anxiety.
Task‐induced modulation of motor evoked potentials in upper‐leg muscles during human gait: a TMS study
Authors: Bonnard Mireille , Camus Mickaël , Coyle Thelma , Pailhous Jean 
Published: March 2003

AbstractThe aim of this study was to determine the relative involvement of the corticospinal (CS) pathway in voluntarily controlled walking compared to unconstrained walking. In the voluntarily controlled walking condition, subjects had to walk at the same speed as in unconstrained walking with a mechanical constraint, which is known to affect specifically the upper‐leg muscles. The motor cortex was activated transcranially using a focal magnetic stimulation coil in order to elicit motor evoked potentials (MEPs) in the rectus femoris (RF) and the biceps femoris (BF). The magnetic stimulation was delivered at the end of the swing (at 90% of the cycle duration), when the EMG backgrounds were similar in the two experimental conditions. For each subject in each condition, MEPs were measured for several stimulus intensities in order to establish the input/output (I/O) curve (MEPs amplitude plotted against stimulus strength). The results showed a significant increase in the MEPs amplitude of both the RF and BF in voluntarily controlled walking compared to unconstrained walking, which is the first evidence of cofacilitation of MEPs in antagonist upper‐leg muscles during human gait. In conclusion, although a lot of studies have emphasized a privileged input of the corticospinal pathway to the distal lower‐leg muscles, this study shows that, if a locomotory task requires fine control of the proximal upper‐leg muscles, a selective facilitation of MEPs is observed in these muscles.
Neurotensin modulates the amplitude and frequency of voltage‐activated Ca2+ currents in frog pituitary melanotrophs: implication of the inositol triphosphate/protein kinase C pathway
Authors: Belmeguenai Amor , Leprince Jérôme , Tonon Marie‐Christine , Vaudry Hubert , Louiset Estelle 
Published: March 2003

AbstractMany excitatory neurotransmitters and neuropeptides regulate the activity of neuronal and endocrine cells by modulating voltage‐operated Ca2+ channels. Paradoxically, however, excitatory neuromediators that provoke mobilization of intracellular calcium from inositol trisphosphate (IP3)‐sensitive stores usually inhibit voltage‐gated Ca2+ currents. We have recently demonstrated that neurotensin (NT) stimulates the electrical and secretory activities of frog pituitary melanotrophs, and increases intracellular calcium concentration in these cells. In the present study, we have investigated the effects of NT on Ca2+ currents in cultured frog melanotrophs by using the perforated patch‐clamp technique. Frog neurotensin (f NT) reduced the amplitude and facilitated the inactivation of both L‐ and N‐type Ca2+ currents. Application of the membrane‐permeant Ca2+ chelator BAPTA‐AM, the sarcoendoplasmic reticulum Ca2+‐ATPase inhibitor thapsigargin, or the IP3 receptor antagonist 2‐APB suppressed the reduction of Ca2+ currents induced by f NT. Incubation of melanotrophs with the diacylglycerol analogue PMA, which causes desensitization of protein kinase C (PKC), or with the PKC inhibitors chelerythrine and calphostin C, reduced the inhibitory effect of f NT. The NT‐induced action potential waveforms, applied as voltage‐clamp commands, decreased the amplitude of Ca2+ currents, and enhanced Ca2+ influx by increasing the Ca2+ spike frequency. Altogether, these data indicate that the inhibitory effect of f NT on Ca2+ currents results from activation of the IP3/PKC pathway. The observation that NT controls Ca2+ signalling through both amplitude and frequency modulations of Ca2+ currents suggests that NT might induce spacial and temporal changes of intracellular Ca2+ concentration leading to stimulation of exocytosis.