bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct populations of hypothalamic dopaminergic neurons exhibit differential responses to brain‐derived neurotrophic factor (BDNF) and neurotrophin‐3 (NT3)
Authors: Loudes C. , Petit F. , Kordon C. , Faivre‐Bauman A. 
Published: March 2003

AbstractWe have previously demonstrated that differentiation of hypothalamic dopaminergic (DA) neurons can be induced in culture by their pituitary intermediate lobe target cells, through both membrane and diffusible factors. We also showed that subpopulations of DA neurons from the arcuate nucleus only, not the periventricular area, can respond to the target. Here we investigated the possibility that both neuronal subsets could also respond differentially to brain‐derived neurotrophic factor (BDNF) or neurotrophin‐3 (NT3). Addition of NT3, but not BDNF, enhanced growth and branching of neurites, tyrosine hydroxylase (TH) as well as increasing levels of cultured arcuate DA neurons. Conversely, BDNF, but not NT3, affected the same parameters in cultured periventricular DA neurons. The neurotrophins thus affect DA neurons in a structure and neuronal type‐selective manner, since general neuronal markers were not affected by either neurotrophin. Neurotrophin effects were reversed by addition of specific antibodies directed against them or their respective receptors, TrkB or TrkC. By themselves, the antibodies inhibited development of DA neurons below that of control cultures, suggesting involvement of endogenous neurotrophins. BDNF and NT3 were indeed found in both arcuate and periventricular neurons and in the intermediate lobe. BDNF was always present as the mature peptide. The mature form of NT3 was only detected in the periventricular area; a precursor‐like heavier form was present in all tissues studied. The present data suggest that NT3, but not BDNF, could participate in the differentiating action of intermediate lobe cells on arcuate DA neurons.
Role of α2C‐adrenoceptor subtype in spatial working memory as revealed by mice with targeted disruption of the α2C‐adrenoceptor gene
Authors: Tanila H. , Mustonen K. , Sallinen J. , Scheinin M. , Riekkinen P. 
Published: March 2003

AbstractThe role of the α2C‐adrenoceptor subtype in mediating the beneficial effect of α2‐adrenoceptor agonists on spatial working memory was studied in adult mice with targeted inactivation of the α2C‐receptor gene (KO) and their wild‐type controls (WT). A delayed alternation task was run in a T‐maze with mixed delays varying from 20 s to 120 s. Dexmedetomidine, a specific but subtype non‐selective α2‐adrenoceptor agonist, dose‐dependently decreased the total number of errors. The effect was strongest at the dose of 5 μg/kg (s.c.), and was observed similarly in KO and WT mice. KO mice performed inferior to WT mice due to a higher number of perseverative errors. Dexmedetomidine slowed initiation of the motor response in the start phase at lower doses in WT mice than in KO mice but no such difference was observed in the return phase of the task, suggesting involvement of α2C‐adrenoceptors in the cognitive aspect of response preparation or in response sequence initiation. According to these findings, enhancement of spatial working memory is best achieved with α2‐adrenoceptor agonists which have neither agonistic nor antagonistic effects at the α2C‐adrenoceptor subtype.
Inducing placebo respiratory depressant responses in humans via opioid receptors
Authors: Benedetti Fabrizio , Amanzio Martina , Baldi Sergio , Casadio Caterina , Maggi Giuliano 
Published: March 2003

AbstractSeveral lines of evidence indicate that placebos produce analgesia through the activation of endogenous opioid systems. Recently, we showed that placebos may also produce respiratory depressant responses, a typical side‐effect of narcotics, when a subject had a prior experience of respiratory depression in the course of narcotic treatment. In the present study, we report that the placebo respiratory depression can be induced after repeated administrations of the partial opioid agonist buprenorphine. The placebo respiratory depressant effect that resulted from the buprenorphine conditioning was completely blocked by a dose of 10 mg of naloxone, indicating that it was mediated by endogenous opioids. These findings show that placebos act, via the activation of opioid receptors, not only on pain mechanisms but on the respiratory centres as well, thus mimicking a typical side‐effect of narcotics. In addition, the experimental procedure we used did not produce any expectation of respiratory depression and, similarly, the subjects did not notice any sign of respiratory discomfort. Thus, the placebo respiratory depression elicited in the present study cannot be explained on the basis of cognitive or motivational mechanisms. Rather, it appears to be a sequence effect due to learning, thus suggesting a conditioning mechanism mediated by endogenous opioids.
Inhibition of collagen IV deposition promotes regeneration of injured CNS axons
Authors: Stichel Christine C. , Hermanns Susanne , Luhmann Heiko J. , Lausberg Friederike , Niermann Heike , D'Urso Donatella , Servos Gisela , Hartwig Hans‐Georg , Müller Hans Werner 
Published: March 2003

AbstractScarring impedes axon regrowth across the lesion site and is one major extrinsic constraint to effective regeneration in the adult mammalian central nervous system. In the present study we determined whether specific biochemical or immunochemical modulation of one major component of the scar, the basal membrane (BM), would provide a means to stimulate axon regeneration in the mechanically transected postcommissural fornix of the adult rat. Basal membrane developed within the first 2 weeks after transection in spatiotemporal coincidence with the abrupt growth arrest of spontaneously regrowing axons. Local injection of anticollagen IV antibodies or α, α′‐dipyridyl, an inhibitor of collagen triple helix formation and synthesis, significantly reduced lesion‐induced BM deposition. This treatment allowed massive axon elongation across the lesion site. Anterograde tracing provided unequivocal evidence that regenerating axons follow their original pathway, reinnervate the appropriate target, the mammillary body, and become remyelinated with compact myelin. Presynaptic electrophysiological recordings of regenerated fibre tracts showed recovery to nearly normal conduction properties. Our results indicate that lesion‐induced BM is an impediment for successful axonal regeneration and its reduction is a prerequisite and sufficient condition for regrowing axons to cross the lesion site.
Brain location and visual topography of cortical area V6A in the macaque monkey
Authors: Galletti Claudio , Fattori Patrizia , Kutz Dieter F. , Gamberini Michela 
Published: March 2003

AbstractThe brain location, extent and functional organization of the cortical visual area V6A was investigated in macaque monkeys by using single cell recording techniques in awake, behaving animals. Six hemispheres of four animals were studied. Area V6A occupies a horseshoe‐like region of cortex in the caudalmost part of the superior parietal lobule. It extends from the medial surface of the brain, through the anterior bank of the parieto‐occipital sulcus, up to the most lateral part of the fundus of the same sulcus. Area V6A borders on areas V6 ventrally, PEc dorsally, PGm medially and MIP laterally. Of 1348 neurons recorded in V6A, 61% were visual and 39% non‐visual in nature. The visual neurons were particularly sensitive to orientation and direction of movement of visual stimuli. The inferior contralateral quadrant was the most represented one. Visual receptive fields were also found in the inferior ipsilateral quadrant and in the upper visual field. Receptive fields were on average smaller in the lower visual field than in the upper one. Both central and peripheral parts of the visual field were represented. Large parts of the visual field were represented in small regions of area V6A, and the same regions of the visual field were re‐represented many times in different parts of this area, without any apparent topographical order. The only reliable sign of retinotopic organization was the predominance of central representation dorsally and far periphery ventrally. The functional organization of area V6A is discussed in the view that this area could be involved in the control of reaching out and grasping objects.
Effects of dorsolateral spinal lesions on stretch reflex threshold and stiffness in awake cats
Authors: Taylor Julian , Munson John , Vierck Jr Charles 
Published: March 2003

AbstractMeasurements of threshold angle and incremental dynamic stiffness (IDS) were derived from triceps surae stretch reflexes, elicited by ramp and hold flexion at the ankle joint of four cats that were tested while awake. Stretch reflexes were assessed from trials that began from different ankle joint start positions or were matched using a post‐hoc analysis for initial background force during testing sessions before and following unilateral lesions of the dorsolateral funiculus at levels ranging from T13 to L3. Unilateral lesions of the dorsolateral funiculus (DLF) produced significant ipsilateral decreases in stretch reflex threshold and increases in reflex gain, measured as incremental dynamic stiffness (IDS). ancova testing indicated that the reduction in threshold, but not the increase in IDS, was dependent upon the level of background force. Reflex testing from different start angles demonstrated that DLF lesions diminished the correlation between threshold and IDS. Intravenous infusion of ketamine dose‐dependently reduced IDS, compared with testing in the unanaesthetized state. Postoperative reflex testing during infusion of ketamine at 22.2 mg/kg per h, when electromyographic responses were reduced to 24% of control levels, abolished differences in IDS between the ipsilateral and contralateral hindlimbs. These and related observations suggest that the postoperative increase in IDS in awake animals was not due to an increase in passive stiffness.
Neurotrophic factors modulate hair cells and their potassium currents in chick otocyst explants
Authors: Sokolowski Bernd H. A. , Csus Jolan , Hafez Osama I. , Haggerty Holly S. 
Published: March 2003

AbstractNeurotrophins, retinoids and their receptors are present in the sensory epithelia of the inner ear during development. We show that these factors modulate the proliferation of hair cells and their K+‐currents when the embryonic day 3 (ED 3) presumptive inner ear (i.e. otocyst) is maintained in organ culture. All trans‐retinoic acid (RA) increases hair cell differentiation and enhances the acquisition of outward currents, including a delayed rectifier and a fast activating, transient type, voltage‐gated potassium current. In contrast, brain‐derived neurotrophic factor (BDNF) and neurotrophin‐3 (NT‐3) decrease ionic current activity, and the addition of RA with the neurotrophins enhances this inhibitory response in an age‐dependent manner. We measured the total number of cells per explant over time to determine precisely when and how these factors inhibit explant growth. We found that high concentrations of BDNF and NT‐3 administered together, and low concentrations of both neurotrophins combined and administered with RA suppress otocyst cell numbers after 24 h in vitro. This suppressive response is induced by RA and NT‐3, not by RA and BDNF. The suppressive or inhibitory influence of NT‐3 and RA is the result of NT‐3 binding to the low affinity receptor, p75NTR, not the result of RA increasing mRNA levels for the high affinity receptor, trkC. However, trk may act with p75NTR, as disruption of trk signalling alleviates the inhibitory response induced by NT‐3 and RA. Our data suggest that various combinations and/or concentration gradients of these factors can differentially regulate inner ear development and hair cell excitability.
Adenosine inhibits L‐type Ca2+ current and catecholamine release in the rabbit carotid body chemoreceptor cells
Authors: Rocher A. , Gonzalez C. , Almaraz L. 
Published: March 2003

AbstractIn an in vitro preparation of the intact carotid body (CB) of the rabbit, adenosine (100 μm) inhibited hypoxia‐induced catecholamine release by 25%. The specific A1 antagonist, 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX; 1 μm) prevented the inhibition and increased the response to hypoxia further. In isolated chemoreceptor cells from the same species, adenosine inhibited voltage‐dependent Ca2+ currents by 29% at 1 μm (concentration producing half‐maximal inhibition, IC50 = 50 nM). This inhibition was mimicked by R(–)N6‐(2‐phenylisopropyl)‐adenosine and 2‐chloroadenosine (1 μm), two purinergic agonists poorly active at the intracellular (‘P′) site, and persisted in the presence of dipyridamole (a blocker of adenosine uptake; 1 μm) and was fully inhibited by 8‐phenyltheophylline (10 μm). The A1 antagonists DPCPX (10 μm) and 8‐cyclopentyl‐1,3‐dimethylxantine (0.1 μm) inhibited the effect of adenosine by 93% (IC50 = 0.14 μm) and 59%, respectively. The inhibition of the Ca2+ current (ICa) was reduced by nisoldipine (an L‐type Ca2+ channel antagonist) by nearly 50%, and was unaltered by omega‐conotoxin GVIA, a blocker of N‐type Ca2+ channels. Adenosine did not affect the voltage‐dependent Na+ current (INa) or K+ current (IK.). We conclude that adenosine A1 receptors are located in chemoreceptor cells and mediate the inhibition of L‐type Ca2+ channels and thereby the release of catecholamines produced by hypoxia. The data also indicate that endogenous adenosine acts as a physiological negative modulator of the chemoreceptor cell function. The previously reported excitatory action of adenosine on the activity of the sensory nerve of the CB is discussed in terms of a balance between the inhibition mediated by A1 receptors and the excitation mediated by A2 receptors.
Support stability influences postural responses to muscle vibration in humans
Authors: Ivanenko Yuri P. , Talis Vera L. , Kazennikov Oleg V. 
Published: March 2003

AbstractWe studied the effect of support stability on postural responses to the vibration of Achilles tendons and of neck dorsal muscles in healthy humans. For this purpose we compared postural responses on a rigid floor and on 6 cm high rocking supports (see‐saws) of different curvatures (different radii: 30, 60 and 120 cm). The subject stood with eyes closed, the centre of the feet coincided with the centre of the see‐saw. We recorded platform tilt, horizontal displacements of the upper body, ankle joint angle and activity of ankle joint muscles. On the rocking platform subjects maintained balance in a sagittal direction by making see‐saw rotations placing the support under the body's centre of gravity. Equilibrium maintenance requires that the torque in the ankle joint increases during forward body displacements, as on the rigid floor, and be accompanied by a plantar flexion (not by a dorsiflexion) in the ankle joint. The directional dependence of vibration‐induced reactions on the see‐saw was the same (relative to space) as on the rigid floor: backward body displacement during Achilles tendon vibration and forward body displacement during neck muscle vibration. A decrease of support stability (with a decrease of the radius from 120 to 30 cm) diminished significantly the effect of Achilles tendon vibration and to a lesser extent the effect of neck muscle vibration. In contrast, the increase of platform stability by hand contact with a stable external object gave rise to prominent body sway in response to Achilles tendon vibration. Neck muscle vibration on the movable support provoked a quick initial forward body sway. This initial quick response was absent during vibration of the Achilles tendons. We conclude that postural responses to muscle vibration reflect the participation of different muscles in posture control and depend on the support properties. Support instability changes the role of proprioceptive information and the state of the system of equilibrium maintenance.
Small cardioactive peptide gene: structure, expression and mass spectrometric analysis reveals a complex pattern of co‐transmitters in a snail feeding neuron
Authors: Dobbins Stephen J. Perry andrew C. , Schofield Michael G. , Piper Marian R. , Benjamin Paul R. 
Published: March 2003

AbstractThe small cardioactive peptides (SCPs) are an important group of neural cotransmitters in molluscs where they are known to play both central and peripheral modulatory roles in the control of feeding behaviour. Here we show that in the snail Lymnaea the SCP gene exists in one interrupted copy that produces a single species of transcript which encodes a prepropeptide containing two structurally related SCPs SGYLAFPRMamide (SCPA) and pQNYLAFPRMamide (SCPB). In situ hybridization was used to localize expression specifically to the soma of several types of motoneurons in the feeding system of Lymnaea, including the giant B2 foregut motoneurons. The peptide content of individual B2 cell bodies was analysed by matrix‐assisted laser desorption/ionization mass spectrometry and the structures of the SCPs predicted from the cloned gene were confirmed in these cells by post‐source decay fragmentation analysis. Identical stimulatory activity for the two SCP peptides was demonstrated by their application to the isolated foregut, suggesting that their co‐release from the B2 cells may play an important part in the co‐modulation of gut motility, together with acetylcholine and the myomodulin family of peptides.
Presynaptic GABAergic control of the locomotor drive in the isolated spinal cord of neonatal rats
Authors: Bertrand Sandrine , Cazalets Jean‐René 
Published: March 2003

AbstractThe in vitro newborn rat isolated brain stem/spinal cord preparation was used to study the involvement of presynaptic inhibition in the control of the synaptic locomotor drive. The recording chamber was partitioned with Vaseline walls to separate the L1–L2 locomotor network from the motoneurons in the lower segments. When locomotor like activity was induced by bath applying a mixture of N‐methyl‐d‐l‐aspartate and serotonin to the L1–L2 segments, intracellular recordings of L3–L5 motoneurons show an alternating pattern of monosynaptic excitatory glutamatergic and inhibitory glycinergic inputs known as the locomotor drive. Gamma‐aminobutyric acid (GABA), baclofen and muscimol (respectively GABAB and GABAA agonists) superfused on the L3–L5 segments depressed the synaptic locomotor drive of motoneurons during the ongoing activity. On the contrary, the GABAB receptor antagonist CGP35348 enhanced the locomotor drive, which suggests that an endogenous release of GABA occurs during locomotor‐like activity. Baclofen, unlike muscimol and GABA, did not affect the passive membrane properties and the firing discharge of synaptically isolated motoneurons. Baclofen and muscimol acted on the two phases (inhibitory and excitatory) of the synaptic drive. The effects of GABAergic agonists on the whole locomotor activity were tested. When superfused on the L3–L5 part of the cord, they affected only the L5 burst amplitude. When bath‐applied to the L1–L2 network, GABA and muscimol decreased the amplitude of the L2 and L5 bursts and increased the locomotor period while baclofen had significant effects only on the period. It was concluded that GABA modulates the information conveyed by the L1–L2 network to its target motoneurons presynaptically via GABAB and possibly GABAA receptors and postsynaptically, via GABAA receptors.
Differential brain expression of a new β‐actin gene from zebrafish (Danio rerio)
Authors: Barrallo Alejandro , González‐Sarmiento Rogelio , García‐Isidoro María , Cidad Pilar , Porteros Angel , Rodríguez Raquel E. 
Published: March 2003

AbstractIt has been shown that actin genes exhibit distinct tissue and stage‐specific patterns of expression. We have cloned a new β‐actin gene from the teleost zebrafish (Danio rerio), a well‐established model for developmental studies, and analysed its expression by Northern blot and in situ hybridization studies. Our results suggest that in adult brain zebrafish, this new gene is expressed during neuronal cell proliferation.
mGluR7‐like metabotropic glutamate receptors inhibit NMDA‐mediated excitotoxicity in cultured mouse cerebellar granule neurons
Authors: Lafon‐Cazal Mireille , Fagni Laurent , Guiraud Marie‐Jeanne , Mary Sophie , Lerner‐Natoli Mireille , Pin Jean‐Philippe , Shigemoto Ryuichi , Bockaert Joël 
Published: March 2003

AbstractGlutamate‐induced glutamate release may be involved in the delayed neuronal death induced by N‐methyl‐d‐aspartate (NMDA). In order to examine a possible modulatory effect of the presynaptic group III mGluRs on glutamate excitotoxicity, the effect of l‐2‐amino‐4‐phosphonobutyrate (L‐AP4) was examined on NMDA‐induced delayed death of mouse cerebellar granule neurons in culture. We found that L‐AP4, at high concentration (in the millimolar range), inhibited in a non‐competitive manner the NMDA‐induced toxicity. This effect was mimicked by high concentration of l‐serine‐o‐phosphate (L‐SOP), and was inhibited by pertussis toxin (PTX) indicating the involvement of a Gi/o protein. This suggests the involvement of mGluR7 in the L‐AP4 effect, and this was consistent with the detection of both mGluR7 protein and mRNA in these cultured neurons. To examine the mechanism of the L‐AP4‐induced protection from excitotoxic damage, the effect of L‐AP4 on glutamate release was examined. L‐AP4 (≥ 1 mm) non‐competitively inhibited by more than 60% the glutamate release induced by NMDA during the insult. We also observed that the 10‐min NMDA receptor stimulation resulted in a dramatic increase in the extracellular glutamate concentration reaching 6000% of the control value 24 h after the insult. This large increase was also inhibited when NMDA was applied in the presence of ≥ 1 mm L‐AP4. Part of the L‐AP4‐induced protection from excitotoxic damage of granule neurons may therefore result from the inhibition of the vicious cycle: dying cells release glutamate, glutamate induced cell death. The present results add to the hypothesis that presynaptic mGluRs, probably mGluR7, may be the targets of drugs decreasing glutamate release and then neuronal death observed in some pathological situations.
Proliferation in the vomeronasal organ of the rat during postnatal development
Authors: Weiler Elke , McCulloch Mary A. , Farbman Albert I. 
Published: March 2003

AbstractWe investigated proliferation of sensory cell precursors in the rat vomeronasal organ (VNO) at various postnatal ages from birth (P1) to P666. In the rat, which continues to grow during most of its adult life, proliferation might be related to growth and/or replacement. Proliferating cells were labelled by BrdU injection, and histological sections of the VNO were evaluated after immunohistochemical detection of BrdU. Proliferation density (number of proliferating cells/section) decreased dramatically from 115 at P1 to 27.2 at P21, although the area increased. Adult values were reached at P66–P333 (10.3 cells/section); at P400–P666 the value was 8.6 cells/section. Distribution of labelled cells changed considerably with age: in neonates the cells were nearly equally distributed throughout the sensory epithelium, whereas from P21 onwards most proliferating cells were concentrated in clusters near the boundaries with non‐sensory epithelium. Labelled cells in the sensory neuronal layer were adjacent to the undulating basement membrane‐bordering capillaries that intrude into the sensory epithelium, indicating that they were true basal cells. The volume of the sensory epithelium increased between P1 and P66, and remained constant thereafter, although the length still increased. Length and volume of the sensory epithelium were related to body size, not to sex; males and females of the same body size had the same VNO size. The complex changes in proliferation pattern during postnatal development indicate differential growth and replacement. We suggest that in adults the labelled cell clusters near the boundaries are a pool for growth, whereas proliferation in the central parts represents a replacement pool.