bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary preferences of Brattleboro rats correlated with an overexpression of galanin in the hypothalamus
Authors: Odorizzi Myriam , Max Jean‐Pierre , Tankosic Pierre , Burlet Claude , Burlet Arlette 
Published: March 2003

AbstractGalanin (GAL) is a neuropeptide cosynthesized with vasopressin (AVP) in neurons of the hypothalamo‐neurohypophysial system. It increases food intake when injected into the brain and elicits an overconsumption of fat. The Brattleboro rat (DI) is genetically unable to produce AVP; the AVP‐deficient‐producing neurons of the hypothalamo‐neurohypophysial system of DI rats are chronically stimulated and DI rats suffer from diabetes insipidus. We studied the central expression of GAL and the dietary preferences in the DI rat. GAL was overexpressed in the hypothalamus of the DI rat. GAL mRNA was higher by 1.8‐fold in the supraoptic (P < 0.05) and by four‐fold in the paraventricular nuclei (P < 0.001) of male and female DI rats compared with those of control Long Evans (LE) rats. However, GAL mRNA was lower in the arcuate nuclei of DI rats and equal to that of LE rats in the dorsomedian nuclei. We also measured a high preference for a lipid diet (45% of the daily consumption) when DI rats ate from a choice of the three macronutrients. Chronic infusion with deamino‐8D‐AVP (agonist of AVP V2 receptors) prevented the diabetes insipidus and the chronic stimulation of the hypothalamo‐neurohypophysial system of the DI rats. However, the treatment did not suppress the overexpression of GAL, nor did it affect the rats’ preference for a lipid diet. We conclude that the DI rat provides a novel animal model in which a spontaneous dietary preference correlates with the overexpression of one of the hypothalamic peptides, GAL.
Network analysis in episodic encoding and retrieval of word‐pair associates: a PET study
Authors: Krause B. J. , Horwitz B. , Taylor J. G. , Schmidt D. , Mottaghy F. M. , Herzog H. , Halsband U. , Müller‐Gärtner H. ‐W. 
Published: March 2003

AbstractThe involvement of distributed brain regions in declarative memory has been hypothesized based on studies with verbal memory tasks. To characterize episodic declarative memory function further, 14 right‐handed volunteers performed a visual verbal learning task using paired word associates. The volunteers underwent positron emission tomography. 15O‐butanol was used as a tracer of regional cerebral blood flow (rCBF). Inter‐regional functional interactions were assessed based on within‐task, across‐subject inter‐regional rCBF correlations. Anatomical connections between brain areas were based on known anatomy. Structural equation modelling was used to calculate the path coefficients representing the magnitudes of the functional influences of each area on the ones to which it is connected by anatomical pathways. The encoding and the retrieval network elicit similarities in a general manner but also differences. Strong functional linkages involving visual integration areas, parahippocampal regions, left precuneus and cingulate gyrus were found in both encoding and retrieval; the functional linkages between posterior regions and prefrontal regions were more closely linked during encoding, whereas functional linkages between the left parahippocampal region and posterior cingulate as well as extrastriate areas and posterior cingulate gyrus were stronger during retrieval. In conclusion, these findings support the idea of a global bihemispheric, asymmetric encoding/retrieval network subserving episodic declarative memory. Our results further underline the role of the precuneus in episodic memory, not only during retrieval but also during encoding.
Requirement for DARPP‐32 in mediating effect of dopamine D2 receptor activation
Authors: Nishi Akinori , Snyder Gretchen L. , Fienberg Allen A. , Fisone Gilberto , Aperia Anita , Nairn Angus C. , Greengard Paul 
Published: March 2003

AbstractIt is well documented that dopamine and dopamine D1 agonists convert the protein phosphatase‐1 inhibitor, DARPP‐32, from its dephosphorylated, inactive form into its Thr34‐phosphorylated, active form, and that these effects on DARPP‐32 constitute essential components of the mechanism by which dopamine and D1 agonists achieve their biological effects. In contrast to dopamine and D1 agonists, dopamine D2 agonists dephosphorylate and inactivate DARPP‐32. Here we have examined the possibility that the biological effects of dopamine D2 receptor agonists might also involve DARPP‐32. For this purpose, we have examined regulation of the activity of the electrogenic ion pump Na+,K+‐ATPase, an established target for dopamine signalling. We have found that dopamine D1 agonists and dopamine D2 agonists inhibit Na+,K+‐ATPase activity in dissociated cells from the mouse neostriatum and that, in each case, the effect is abolished in cells from mice deficient in DARPP‐32. We conclude that DARPP‐32 may play an obligatory role in dopaminergic signalling mediated both by D1 receptors and by D2 receptors.
Caffeine‐mediated induction of c‐fos, zif‐268 and arc expression through A1 receptors in the striatum: different interactions with the dopaminergic system
Authors: Dassesse Donald , Vanderwinden Jean‐Marie , Goldberg Ilan , Vanderhaeghen Jean‐Jacques , Schiffmann Serge N. 
Published: March 2003

AbstractAdenosine and the adenosine receptor antagonist, caffeine, modulate locomotor activity and striatal neuropeptide expression through interactions with the dopaminergic system by mechanisms which remain partially undetermined. We adressed this question by using quantitative immunocytochemistry and in situ hybridization, combined with retrograde tracing of striatal neurons, to characterize the mechanism(s) leading to the striatal increase in the immediate early genes (IEG), c‐fos, zif‐268 and arc, following a single injection of caffeine or the A1 antagonist, 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX). Caffeine and DPCPX induced c‐fos, zif‐268 and arc expression, both at mRNA and protein levels, in large proportions of striatonigral and striatopallidal neurons. The involvement of dopamine systems was evaluated by manipulations of the dopaminergic transmission. Quinpirole, a D2 agonist, almost completely blocked the caffeine‐induced IEG increase in both striatopallidal and striatonigral neurons. Conversely, the lesion of the nigrostriatal pathway and the D1 antagonist SCH23390 abolished the caffeine effects in striatonigral neurons but had no or slight effect, respectively, on its action in striatopallidal neurons. These observations demonstrate that caffeine‐ and DPCPX‐mediated IEG inductions involved different mechanisms in striatonigral and striatopallidal neurons through blockade of A1 receptors. Immediate early gene inductions result from a stimulation of dopamine release in striatonigral neurons and from activation of glutamate release and probably also acetylcholine release in striatopallidal neurons. These results also support the idea that, besides A2A receptors, adenosine acting at the A1 receptor plays pivotal functions in the basal ganglia physiology and that blockade of these receptors by specific or nonspecific antagonists, DPCPX and caffeine, may influence a broad range of neuronal functions in the striatum.
LSD and DOB: interaction with 5‐HT2A receptors to inhibit NMDA receptor‐mediated transmission in the rat prefrontal cortex
Authors: Arvanov Viktor L. , Liang Xiaofu , Russo Angelo , Wang Rex Y. 
Published: March 2003

AbstractBoth the phenethylamine hallucinogen (–)‐1‐2,5‐dimethoxy‐4‐bromophenyl‐2‐aminopropane (DOB), a selective serotonin 5‐HT2A,2C receptor agonist, and the indoleamine hallucinogen d‐lysergic acid diethylamide (LSD, which binds to 5‐HT1A, 1B, 1D, 1E, 1F, 2A, 2C, 5, 6, 7, dopamine D1 and D2, and α1 and α2 adrenergic receptors), but not their non‐hallucinogenic congeners, inhibited N‐methyl‐d‐aspartate (NMDA)‐induced inward current and NMDA receptor‐mediated synaptic responses evoked by electrical stimulation of the forceps minor in pyramidal cells of the prefrontal cortical slices. The inhibitory effect of hallucinogens was mimicked by 5‐HT in the presence of selective 5‐HT1A and 5‐HT3 receptor antagonists. The inhibitory action of DOB, LSD and 5‐HT on the NMDA transmission was blocked by the 5‐HT2A receptor antagonists r‐(+)‐α‐(2,3‐dimethoxyphenil)‐1‐[4‐fluorophenylethyl]‐4‐piperidinemethanol (M100907) and ketanserin. However, at low concentrations, when both LSD and DOB by themselves only partially depressed the NMDA response, they blocked the inhibitory effect of 5‐HT, suggesting a partial agonist action. Whereas N‐(4‐aminobutyl)‐5‐chloro‐2‐naphthalenesulphonamide (W‐7, a calmodulin antagonist) and N‐[2‐[[[3‐(4′‐chlorophenyl)‐ 2‐propenyl]methylamino]methyl]phenyl]‐N‐(2‐hydroxyethyl)‐4′‐methoxy‐benzenesulphonamide phosphate (KN‐93, a Ca2+/CaM‐KII inhibitor), but not the negative control 2‐[N‐4′methoxybenzenesulphonyl]amino‐N‐(4′‐chlorophenyl)‐2‐propenyl‐N‐methylbenzylamine phosphate (KN‐92), blocked the inhibitory action of LSD and DOB, the selective protein kinase C inhibitor chelerythrine was without any effect. We conclude that phenethylamine and indoleamine hallucinogens may exert their hallucinogenic effect by interacting with 5‐HT2A receptors via a Ca2+/CaM‐KII‐dependent signal transduction pathway as partial agonists and modulating the NMDA receptors‐mediated sensory, perceptual, affective and cognitive processes.
Differential effects of Bcl‐2 overexpression on fibre outgrowth and survival of embryonic dopaminergic neurons in intracerebral transplants
Authors: Schierle Gabriele S. , Leist Marcel , Martinou Jean‐Claude , Widner Håkan , Nicotera Pierluigi , Brundin Patrik 
Published: March 2003

AbstractThe causes of death of transplanted neurons are not known in detail, but apoptotic mechanisms involving caspase activation are likely to play a role. We examined whether overexpression of the anti‐apoptotic protein Bcl‐2 may enhance the survival of dopaminergic [tyrosine hydroxylase (TH)‐immunoreactive] grafted neurons. For this purpose, we prepared cells from embryonic day 13 ventral mesencephalon (VM) of mice overexpressing human Bcl‐2, or from their wild‐type littermates. The bcl‐2 transgene was strongly expressed in these cells, and resulted in protection of neuronal cultures from death triggered by serum deprivation or exposure to staurosporine. To model pretransplantation stress more closely in vitro, we stored dissociated embryonic mesencephalic cells for 8 h in the same type of medium used for intracerebral transplantation. This resulted in massive cell death as quantified by lactate dehydrogenase (LDH) release, and increased DNA fragmentation. Although this cell loss was strongly reduced by a caspase inhibitor, Bcl‐2 had no significant protective effect. Finally, mesencephalic cell suspensions were xenografted into the striatum of immunosuppressed hemiparkinsonian rats. Neither the survival of TH‐immunopositive transplanted neurons nor the functional recovery of the rats was improved by Bcl‐2, although the Bcl‐2 protein was strongly expressed in transgenic grafts 5 weeks after implantation, and dopaminergic fibre outgrowth from the grafts was significantly improved. These data suggest that cell death in neuronal transplants involves apoptotic mechanisms that can bypass negative regulation by Bcl‐2.
Action of serotonin on the hyperpolarization‐activated cation current (Ih) in rat CA1 hippocampal neurons
Authors: Gasparini Sonia , DiFrancesco Dario 
Published: March 2003

AbstractWe studied the effects of serotonin (5‐HT) on hippocampal CA1 pyramidal neurons. In current‐clamp mode, 5‐HT induced a hyperpolarization and reduction of excitability due to the opening of inward rectifier K+ channels, followed by a late depolarization and partial restoration of excitability. These two components could be dissociated, as in the presence of BaCl2 to block K+ channels, 5‐HT induced a depolarization accompanied by a reduction of membrane resistance, whereas in the presence of ZD 7288 [4‐(N‐ethyl‐N‐phenylamino)‐1,2‐dimethyl‐6‐(methylamino) pyrimidinium chloride], a selective blocker of the hyperpolarization‐activated cation current (Ih), 5‐HT only hyperpolarized neurons. We then studied the action of 5‐HT on Ih in voltage‐clamp conditions. 5‐HT increased Ih at −90 mV by 29.1 ± 2.9% and decreased the time constant of activation by 20.1 ± 1.7% (n = 16), suggesting a shift in the voltage dependence of the current towards more positive potentials; however, the fully activated current measured at −140 mV also increased (by 14.1 ± 1.7%, n = 14); this increase was blocked by ZD 7288, implying an effect of 5‐HT on the maximal conductance of Ih. Both the shift of activation curve and the increase in maximal conductance were confirmed by data obtained with ramp protocols. Perfusion with the membrane‐permeable analogue of cAMP, 8‐bromoadenosine 3′5′‐cyclic monophosphate (8‐Br‐cAMP), increased Ih both at −90 and −140 mV, although the changes induced were smaller than those due to 5‐HT. Our data indicate that 5‐HT modulates Ih by shifting its activation curve to more positive voltages and by increasing its maximal conductance, and that this action is likely to contribute to the 5‐HT modulation of excitability of CA1 cells.
Myelination and behaviour of tenascin‐C null transgenic mice
Authors: Kiernan B. W. , Garcion E. , Ferguson J. , Frost E. E. , Torres E. M. , Dunnett S. B. , Saga Y. , Aizawa S. , Faissner A. , Kaur R. , Franklin R. J. M. , Ffrench‐Constant C. 
Published: March 2003

AbstractThe extracellular matrix glycoprotein tenascin‐C is widely expressed during development and repair, making it surprising that few abnormalities have been found in transgenic mice lacking this molecule. We have therefore re‐examined the transgenic mice described by Saga et al. [Saga, Y., Yagi, T., Ikawa, Y., Sakakura, T. & Aizawa, S. (1992) Genes Dev., 6 1821–1831] in which tenascin‐C was knocked‐out by homologous recombination, focusing on two aspects of the nervous system likely to reveal any abnormalities that might follow the loss of tenascin‐C. First, we have determined the pattern of myelin and distribution of oligodendrocyte precursor cells in those areas, such as the optic nerve and retina where local concentrations of tenascin‐C have been proposed to act as barriers to oligodendrocyte precursor migration and so prevent inappropriate myelination. Secondly, we have examined the behaviour of the mice in a number of well‐characterized tests, e.g. beam‐walking, passive avoidance and the Morris water maze. We find no abnormalities of myelination or oligodendrocyte precursor distribution in adult mice, showing that local concentrations of tenascin‐C are not the sole mechanism responsible for the pattern of myelination in these regions of CNS. However, we do find a number of behavioural abnormalities in these mice and show that hyperlocomotion and deficits in coordination during beam walking can be ascribed to tenascin‐C deficiency. The effects on coordination are, however, not seen on a 129 genetic background. Taken together, these results significantly extend the phenotype associated with tenascin‐C deficiency but argue against a role in myelination.
Long‐term neuroprotective effects of glycosaminoglycans–IGF‐I cotreatment in the motor neuron degeneration (mnd ) mutant mouse
Authors: Gorio A. , Germani E. , Lesma E. , Rossoni G. , Muller E. E. , Di Giulio A. M. 
Published: March 2003

AbstractThis study shows that cotreatment with insulin‐like growth factor‐I (IGF‐I) and glycosaminoglycans (GAGs) prevents the onset of neuromuscular deficit in the m/m mutant mouse. These mice show a mid‐to‐late‐life onset of progressive paralysis of the hind limb, that is correlated with altered innervation and reduced nerve‐evoked isometric twitch tension in the extensor digitorum longus (EDL) muscle. Almost 50% of EDL nerve endings are negative for antisynaptophysin staining, while retrograde labelling with β‐cholera‐toxin coupled to type IV horseradish and quantitative histological analysis show a small loss of EDL and lumbar cord motor neurons. At 10 months of age also forelimb function evaluated as grip strength is significantly reduced. Animals treated either with glycosaminoglycans alone or with IGF‐I alone at low and high doses showed only a partial improvement of their condition. However, cotreatment of m/m mice with IGF‐I and GAGs fully prevented the neuromuscular abnormalities, the twitch tension loss, the motor neuron decrease and the reduction of forelimb grip strength.
Peptide‐mediated glial responses to Leydig neuron activity in the leech central nervous system
Authors: Schmidt Joachim , Deitmer Joachim W. 
Published: March 2003

AbstractNeuronal activity may lead to a variety of responses in neighbouring glial cells; in general, an ensemble of neurons needs to be active to evoke a K+‐ and/or neurotransmitter‐induced glial membrane potential change. We have now detected a signal transfer from a single neuromodulatory Leydig neuron to the giant neuropil glial cells in the central nervous system of the leech Hirudo medicinalis. Activation of a Leydig neuron, two of which are located in each segmental ganglion, elicits a hyperpolarization in the giant neuropil glial cells. This hyperpolarization could be mimicked by bath application of the peptide myomodulin A (1 nm–1.0 μm). Myomodulin‐like immunoreactivity has recently been found to be present in a set of leech neurons, including Leydig neurons (Keating & Sahley 1996, J. Neurobiol., 30, 374–384). The glial responses to Leydig neuron stimulation persisted in a high‐divalent cation saline, when polysynaptic pathways are suppressed, indicating that the effects on the glial cell were direct. The glial responses to myomodulin A application persisted in high‐Mg2+/low‐Ca2+ saline, when chemical synaptic transmission is suppressed, indicating a direct effect of myomodulin A on the glial membrane. The glial hyperpolarization evoked by myomodulin A was dose dependent (EC50 = 50 nm) and accompanied by a membrane conductance increase of ≈ 25%. Ion substitution experiments indicated that myomodulin A triggered a Ca2+‐independent K+ conductance. Thus, our results suggest, for the first time, direct signal transmission from an identified modulatory neuron to an identified glial cell using a myomodulin‐like peptide.
A new conotoxin isolated from Conus consors venom acting selectively on axons and motor nerve terminals through a Na+‐dependent mechanism
Authors: Le Gall Frédéric , Favreau Philippe , Benoit Evelyne , Mattei César , Bouet Françoise , Menou Jean‐Louis , Ménez André , Letourneux Yves , Molgó Jordi 
Published: March 2003

AbstractA novel conotoxin was isolated and characterized from the venom of the fish‐hunting marine snail Conus consors. The peptide was identified by screening chromatography fractions of the crude venom that produced a marked contraction and extension of the caudal and dorsal fins in fish, and noticeable spontaneous contractions of isolated frog neuromuscular preparations. The peptide, named CcTX, had 30 amino acids and the following scaffold: X11CCX7CX2CXCX3C. At the frog neuromuscular junction, CcTx at nanomolar concentrations selectively increased nerve terminal excitability so that a single nerve stimulation triggered trains of repetitive or spontaneous synaptic potentials and action potentials. In contrast, CcTx had no noticeable effect on muscle excitability even at concentrations 100 × higher than those that affected motor nerve terminals, as revealed by direct muscle stimulation. In addition, CcTx increased miniature endplate potential (MEPP) frequency in a Ca2+‐free medium supplemented with ethylene glycol‐bis‐(β‐aminoethyl ether)‐N,N,N′,N′‐tetraacetic acid (EGTA). Blockade of voltage‐dependent sodium channels with tetrodotoxin (TTX) either prevented or suppressed the increase of MEPP frequency induced by the toxin. CcTx also produced a TTX‐sensitive depolarization of the nodal membrane in single myelinated axons giving rise, in some cases, to repetitive and/or spontaneous action potential discharges. In addition, CcTx increased the nodal volume of myelinated axons, as determined using confocal laser scanning microscopy. This increase was reversed by external hyperosmolar solutions and was prevented by pretreatment of axons with TTX. It is suggested that CcTx, by specifically activating neuronal voltage‐gated sodium channels at the resting membrane potential, produced Na+ entry into nerve terminals and axons without directly affecting skeletal muscle fibres. CcTx belongs to a novel family of conotoxins that targets neuronal voltage‐gated sodium channels.
Postural responses to combined vestibular and hip proprioceptive stimulation in man
Authors: Popov K. E. , Kozhina G. V. , Smetanin B. N. , Shlikov V. Y. 
Published: March 2003

AbstractVestibular–proprioceptive interaction in human postural control in the frontal plane was studied by analysing the lateral body sway evoked in a standing subject by a weak, near‐threshold galvanic vestibular stimulation combined with a balanced, bilateral vibration of the medial gluteus muscles. The intensities of the stimuli were adjusted so that none of them produced a consistent postural response when delivered alone. The pattern of the lateral body sway evoked by the combined stimulation was compared with postural responses to suprathreshold vestibular stimulation and asymmetric (unilateral) vibration of the hip abductors. During the vestibular stimulation alone the head movement started earlier and was larger than movement of the hip. During unilateral vibration the head movement was delayed with respect to the hip movement and the amplitude of head deviation was less than that of the hip. The pattern of postural response to combined vestibular stimulation and balanced vibration resembled that observed under unbalanced, unilateral vibration in terms of both the latencies and amplitudes of deviation of the body segments from their respective baseline positions. It is suggested that the asymmetric vestibular signal provided by galvanic stimulation of the labyrinth introduces a bias into the reference frame for central interpretation of proprioceptive signals so that a symmetric proprioceptive input gives rise to a lateral body sway when referenced to an asymmetric vestibular input.
Rises in [Ca2+]i mediate capsaicin‐ and proton‐induced heat sensitization of rat primary nociceptive neurons
Authors: Guenther S. , Reeh P. W. , Kress M. 
Published: March 2003

AbstractCapsaicin (CAPS) as well as acidic pH induces Ca2+ influx in a subset of rat dorsal root ganglion neurons. Here we show that CAPS as well as three different approaches to induce experimental tissue acidification (phosphate buffered solution pH 5.4, CO2‐gassed solution pH 6.1 and NPE‐caged protons) yielded a transient heat sensitization of peripheral nociceptive terminals in rat skin in vitro. The heat sensitization induced by CAPS (1 μm) could be prevented by preloading the neurons with the neuroprotective calcium chelator BAPTA‐AM (1 mm). However, this pretreatment had no effect on the sensitization following exposure to acidic solutions (pH 5.4 and pH 6.1). Therefore, the membrane‐permeant proton buffer SNARF‐AM (200 μm) was used together with BAPTA‐AM in order to prevent changes in intracellular pH. Under these conditions heat sensitization by low pH did not occur. To investigate the underlying membrane mechanisms, current recordings together with simultaneous calcium measurements using FURA‐2 were performed in neurons isolated from rat dorsal root ganglia. In a subset of these neurons, an increase in [Ca2+]i and concomitant facilitation of heat‐activated ionic currents was observed after application of CAPS as well as pH 5.6. Rises in [Ca2+]i thus appear to play an essential role in plastic changes not only of central neurons but also of peripheral nociceptive terminals which may account for heat hyperalgesia.