bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Afferent Connectivity in the Adult Spinal Cord by Nerve Growth Factor
Authors: Lewin Gary R. , Winter Janet , McMahon Stephen B. 
Published: April 2006

AbstractDuring development, nerve growth factor (NGF) regulates the density and character of peripheral target innervation (Barde, Neuron, 2, 1525–1534, 1989; Ritter et al., Soc. Neurosci. Abstr., 17, 546.2, 1991); its role in adult animals is less well defined. Here we have asked if the availability of growth factors such as NGF in peripheral tissues can influence the pattern of primary afferent connections in the CNS. Using osmotic minipumps, we raised the levels of NGF in rat skeletal muscle in vivo, a tissue where the levels of this factor are normally very low (Korsching and Thoenen, Proc. Natl. Acad. Sci. USA, 80, 3513–3516, 1983; Shelton and Reichardt, Proc. Natl. Acad. Sci. USA, 81, 7951–7955, 1984; Goedert et al., Mol. Brain Res., 1, 85–92, 1986). After 2 weeks of treatment we asked if the sensory neurons innervating this tissue showed an altered strength and distribution of connections with dorsal horn neurons. The contralateral (vehicle‐treated) muscle, and totally untreated animals, served as controls. In normal and vehicle‐treated animals, electrical stimulation of muscle afferents excited relatively few neurons in the dorsal horn, and these generally showed only weak responses. In contrast, on the NGF‐treated side many more dorsal horn neurons in the lumbar enlargement of the spinal cord were excited by muscle afferents. The increased responsiveness could not be explained by a generalized increase in dorsal horn excitability, since spontaneous activity was not enhanced, nor by a change in A‐fibre‐mediated inhibitions from the treated afferents. Thus, these afferents appeared to establish new synaptic connections or strengthened previously weak ones as a result of increased neurotrophic factor availability. The data suggest that, in the adult rat, the levels of growth factors in peripheral targets may be used to regulate an appropriate degree of afferent connectivity within the central nervous system.
Identification of the Serum Complex Which Induces Cerebellar Granule Cell In Vitro Differentiation and Resistance to Excitatory Amino Acids
Authors: Mercanti D. , Galli C. , Liguori M. , Ciotti M. T. , Gullà P. , Calissano P. 
Published: April 2006

AbstractThe protein complex promoting in vitro terminal differentiation of cerebellar granule cells has been isolated from rabbit serum. We designate the complex the neurite outgrowth and adhesion complex (NOAC). The apparent molecular weight, evaluated by gel filtration, is 80–100 kDa. Rat cerebellar granule cells cultured in NOAC exhibit much lower glial cell contamination and survive, in their differentiated state, much longer than in 10% foetal calf serum. While they bind tetanus toxin, express specific antigens such as synapsin l, synaptophisin and A2B5, and release [3H]d‐aspartate in a fashion similar to that shown by cells cultured in foetal calf serum, they show a 60% reduction in the total number of kainate binding sites. Excitatory amino acid (EAA)‐triggered and depolarization‐stimulated calcium influx, measured in the presence of different agonists, is 50–80% lower in NOAC‐cultured cells. NOAC cells are resistant to excitotoxic stimuli carried by EAAs or by depolarizing treatments with 50 mM KCI or 6 μM veratridine. The marked resistance of NOAC‐cultured neurons to EAAs can be attributed to decreased calcium entry through EAA‐coupled and voltage‐gated calcium channels and possibly to other, as yet unidentified, phenotypic properties of these cells. These findings demonstrate that rabbit serum contains one or more polypeptide(s) endowed with the properties of promoting in vitro survival and differentiation of rat cerebellar granule cells and of conferring an EAA‐resistant phenotype.
Activation of Protein Kinase C Modulates Light Responses in Horizontal Cells of the Turtle Retina
Authors: Akopian Abram , McReynolds John , Weiler Reto 
Published: April 2006

AbstractThe effect of phorbol esters on the light‐evoked responses of horizontal cells were studied in the turtle eyecup preparation. Phorbol esters caused a reduction in receptive field size and a significant decrease in the amplitude of responses to annular and full‐field illumination; however, they caused only minor changes in responses to small spots in the receptive field centre. The dark membrane potential was not affected. The results suggest that phorbol esters may affect both coupling resistance and membrane resistance in horizontal cells. The effects of phorbol esters were blocked by the protein kinase C inhibitor staurosporine, and inactive phorbol ester had no effect, making it very likely that the phorbol ester effects were mediated through activation of protein kinase C. The above effects of the phorbol esters were considerably reduced by the dopamine antagonists haloperidol and fluphenazine, suggesting that they were in part mediated by release of dopamine.
Calcitonin Gene‐related Peptide Causes Intraspinal Spreading of Substance P Released by Peripheral Stimulation
Authors: Schaible H.‐G. , Hope P. J. , Lang C. W. , Duggan A. W. 
Published: April 2006

AbstractExperiments were performed in barbiturate‐anaesthetized, spinalized cats to investigate the effect of calcitonin gene‐related peptide (CGRP) on the spatial distribution of immunoreactive substance P (ir‐SP) in the spinal cord released by electrical nerve stimulation and noxious mechanical stimuli. The presence of ir‐SP was assessed with microprobes bearing C‐terminus‐directed antibodies to SP. CGRP was microinjected into the grey matter of the spinal cord near microprobe insertion sites at depths of 2500, 2000, 1500 and 1000 μm using minute amounts (in total 0.2–0.5 μl) of Ringer solution containing CGRP at a concentration of 10−5 or 10−3 M. In the untreated cord electrical stimulation of the tibial nerve (suprathreshold for all C fibres) elicited release of ir‐SP which was centred in and around the lamina II. After microinjection of CGRP, stimulation‐associated ir‐SP was detected in a region extending from the cord surface down to the ventral horn. This pattern was similar to that observed after the microinjection of synthetic peptidase inhibitors (Duggan et al., Brain Res., 579, 261–269, 1992). The large expansion of sites accessed by ir‐SP was time‐dependent, reaching a maximal effect within 10–40 min after microinjection of CGRP, and reversal was observed in subsequent probes. A similar expansion of the regions accessed by ir‐SP after microinjection of CGRP was also observed when release of ir‐SP was evoked by noxious mechanical stimulation of the toes. These results indicate that one important function of CGRP in the spinal cord may be the control of the intraspinal sites and neuronal circuits accessed by released substance P, possibly by inhibition of endopeptidases responsible for peptide degradation.
Cycloheximide Reduces the Effects of Anoxic Insult In Vivo and In Vitro
Authors: Papas S. , Crépel V. , Hasboun D. , Jorquera I. , Chinestra P. , Ben‐Ari Y. 
Published: April 2006

Abstract In vivo and in vitro techniques were utilized to examine the influence of a protein synthesis blocker, cycloheximide (CHX), on the damaging effects of anoxia in the rat. CHX administered 1 h before transient (30 min) forebrain ischaemia increased the survival of animals, decreased body weight loss and reduced the occurrence of delayed degeneration in the CA1 pyramidal region. The same dose of CHX injected 1 h after ischaemia induced status epilepticus, a decrease in survival rate, and did not reduce weight loss or CA1 damage in any of the surviving rats. Electrophysiological techniques were then used to determine the effects of various periods of anoxia and aglycaemia (AA) on CA1 field excitatory postsynaptic potentials (EPSPs) in hippocampal slices incubated in the presence or absence of CHX. In CHX‐treated slices, recuperation of EPSP amplitude (45±16%) was significantly greater than in control slices (9±9%) following an AA episode of 3 min 45 s. No difference was seen in the percent recuperation of EPSPs in the control and CHX‐treated slices after shorter or longer episodes of AA. From these studies, it appears that CHX protects against the damaging effect of ischaemia in vivo or AA in vitro.
On the Distribution of GAP‐43 and its Relation to Serotonin in Adult Monkey and Cat Spinal Cord and Lower Brainstem
Authors: Arvidsson Ulf , Risling Mårten , Cullheim Staffan , Dagerlind Åke , Lindå Hans , Shupliakov Oleg , Ulfhake Brun , Hökfelt Tomas 
Published: April 2006

AbstractBy use of a monoclonal antibody, the distribution of growth‐associated protein (GAP)‐43‐like immunoreactivity (LI) has been studied in the spinal cord of adult grey monkeys (Macaca fascicularis) and adult cats by use of immunofluorescence and peroxidase‐antiperoxidase techniques. The brainstem was also studied with in situ hybridization histochemistry. In both monkeys and cats, a dense innervation of GAP‐43‐immunoreactive (IR) fibres was seen in close apposition to large cell bodies and their processes in the motor nucleus of the ventral horn. Double‐labelling experiments revealed a high degree of coexistence between GAP‐43‐ and 5‐hydroxytryptamine (5‐HT, serotonin)‐LI in the monkey motor nucleus, while in the cat no such colocalization could be verified. At the electron microscopic level, GAP‐43 labelling was seen as a coating of vesicles and axolemma inside the terminals. In both monkey and cat, cell bodies expressing mRNA encoding GAP‐43 were demonstrated in the medullary midline raphe nuclei. A similar location was also encountered for mRNA for aromatic l‐amino acid decarboxylase, an enzyme found in both catecholamine‐ and serotonin‐containing neurons. The present results suggest that GAP‐43 is present in the 5‐HT bulbospinal pathway of the monkey. In the cat, GAP‐43 mRNA‐expressing cell bodies were demonstrated in areas where descending 5‐HT neurons are located, but no convincing colocalization of 5‐HT‐ and GAP‐43‐LI was found at spinal cord levels, despite the existence of extensive fibre networks containing either of the two compounds. Possible explanations for this species discrepancy are discussed. The function of GAP‐43 in nerve terminals impinging on the motoneurons is unknown. However, it may play a role in transmitter release and/or plasticity, since such roles have been proposed for this protein in other systems.
Protein Kinase C Facilitation of Acetylcholine Release at the Rat Neuromuscular Junction
Authors: D'Angelo Egidio , Rossi Paola , Tanzi Franco , Taglietti Vanni 
Published: April 2006

AbstractProtein kinase C (PKC) is a Ca2+‐dependent enzyme involved in synaptic transmission, which can be experimentally activated by the phorbol ester, phorbol 12‐myristate‐13‐acetate (TPA). We studied the effects of TPA application on acetylcholine (ACh) release at the rat neuromuscular junction by means of the focal recording technique; possible effects of TPA at the postsynaptic site had been ruled out in preliminary studies. In extracellular solutions containing 2 mM Ca2+ and at the stimulation frequency of 0.1 Hz, TPA increased endplate current (EPC) amplitude. In non‐stimulated preparations spontaneous current frequency was increased at a similar rate. The similar time course of TPA action on evoked and spontaneous currents suggests that an increased presynaptic Ca2+ efficacy can be considered to be the probable mechanism of action. The interactions of PKC with ACh release were further investigated. In 0.1 mM Ca2+ extracellular solutions, TPA enhanced evoked currents only at stimulation frequencies (e.g. 40 Hz) that were themselves capable of inducing facilitation. This facilitation is classically associated with presynaptic Ca2+ accumulation, indicating that PKC interacts synergistically with Ca2+ to facilitate ACh release. In particular, since mean quantum size and release probability remained almost unchanged during TPA facilitation, it was concluded that PKC acted by enlarging the immediately available store. Interestingly, TPA also increased the presynaptic currents that were observed to be largely brought about by Ca2+‐dependent K+ currents: evidence was obtained to suggest that increases in these currents provide negative feedback against excess release activation rather than being an expression of enhanced Ca2+ influx.
Survival of Purkinje Cells in Cerebellar Cultures is Increased by Insulin‐like Growth Factor I
Authors: Torres‐Aleman I. , Pons S. , Santos‐Benito F. F. 
Published: April 2006

AbstractInsulin‐like growth factor I (IGF‐I) is a trophic factor for both neurons and glia. Its presence in the developing and adult cerebellum suggests a role for this growth factor in this area of the brain. Recently, we have described the existence of an IGF‐I‐containing pathway in afferents of Purkinje neurons arising from the inferior olive. In addition, IGF‐I receptors are present in the molecular layer of the cerebellar cortex. These observations prompted us to investigate whether the Purkinje cell is a target for IGF‐I. Addition of IGF‐I to rat cerebellar cultures produced a 7‐fold increase in the number of Purkinje cells (calbindin‐positive) together with an increase in the calbindin content of the cultures. IGF‐I also doubled the number of surviving neurons and produced a moderate, non‐significant increase in [3H]thymidine incorporation by the cultures. On the other hand, basic fibroblast growth factor (bFGF), which is also present in the cerebellum, produced a dramatic increase in both the proportion of astrocytes and in the mitotic activity of the cultures, without affecting neuron survival. We conclude that IGF‐I is a specific promoter of Purkinje cell survival and that its effects differ from those produced by bFGF in fetal cerebellar cultures. These findings reinforce our hypothesis that the Purkinje cell is a target neuron for IGF‐I action in the developing cerebellum.
Diversity of mRNAs in the Axonal Compartment of Peptidergic Neurons in the Rat
Authors: Mohr Evita , Richter Dietmar 
Published: April 2006

AbstractVasopressin and oxytocin mRNAs, which are normally translated in the perikarya of magnocellular neurons, have recently been demonstrated to be also present in axons and nerve terminals which are located in the posterior pituitary. The physiological significance of this observation has not yet been resolved. In order to gain further insight into the function and plasticity of the peptidergic neuron the question was addressed whether axonal localization is a unique feature of the above‐mentioned transcripts. Biochemical evidence is presented that magnocellular axons and nerve terminals also contain mRNA species encoding a member of the neurofilament protein family and the prodynorphin precursor. These data imply that axons may harbour a variety of additional protein‐encoding transcripts. Furthermore, it is shown that in the mutant (Brattleboro) rat, which lacks detectable levels of vasopressin but which still transcribes the corresponding gene, axonal vasopressin but not oxytocin mRNA contents are dramatically reduced. Most likely, vasopressin transcripts are absent from the nerve terminals as a consequence of the impaired precursor biosynthesis in the cytoplasm of the mutant rat.
Endothelins Inhibit Junctional Permeability in Cultured Mouse Astrocytes
Authors: Giaume Christian , Cordier Jocelyne , Glowinski Jacques 
Published: April 2006

AbstractEndothelins, a family of potent vasoconstrictor peptides initially characterized in peripheral tissues, have also been reported to be synthesized in the brain. In this structure several cell types, including astrocytes, endothelial cells and certain neurons, are potential targets for these peptides. In astrocytes, endothelins induce changes in the concentration of several second messengers (calcium, diacylglycerol, arachidonic acid, cAMP) known to be involved in the regulation of gap junction channels. Using the scrape loading/dye transfer technique we have observed that two isoforms of endothelin, endothelin‐1 and endothelin‐3, strongly inhibit the extent of dye‐coupling between confluent astrocytes, suggesting that gap junction permeability was reduced. This inhibitory effect on dye coupling was reproduced by the snake venom sarafotoxin. When used at 10−7 M, these three compounds had inhibitory effects on gap junction channels which were comparable to those induced by the well known uncoupling agents octanol and halothane. In the absence of extracellular calcium, the effects of endothelins were largely prevented, suggesting that second messengers linked to the activation of phospholipases C and/or A2, which both are dependent on external calcium, could be involved in the uncoupling mechanism.
Cell Counts of Purkinje and Inferior Olivary Neurons in the ‘Hyperspiny Purkinje Cells’ Mutant Mouse
Authors: Frederic F. , Hainaut F. , Thomasset M. , Guenet J. L. , Delhaye‐Bouchaud N. , Mariani J. 
Published: April 2006

AbstractThe mutant mouse ‘hyperspiny Purkinje cells’(hpc) has morphologically abnormal Purkinje cells and below normal intracerebellar calbindin‐D28k, a calcium‐binding protein that, in the cerebellum, is found only in the Purkinje cells. We counted the Purkinje cells on serial sections stained with thionin or labelled with anti‐calbindin‐D28k antibodies to investigate whether the depletion of the cerebellar content of calbindin‐D28k was correlated with a reduced number of Purkinje cells. We also counted the inferior olivary neurons, as they are one of the major afferents of the Purkinje cells and also contain calbindin‐D28k. The hpc mutant mice had 27% fewer cerebellar Purkinje cells and 12% fewer inferior olivary neurons than did controls. Their Purkinje cells were evenly immunostained but slightly atrophic. These data suggest that the depleted cerebellar calbindin‐D28k content could be explained both by the loss of some Purkinje cells and the reduced size of the remaining ones.
Ca2+‐Mediated Plateau Potentials in a Subpopulation of Interneurons in the Ventral Horn of the Turtle Spinal Cord
Authors: Hounsgaard J. , Kjaerulff O. 
Published: April 2006

AbstractThe response properties of interneurons in the ventral horn were studied in transverse slices of segments D8 to S2 from the turtle spinal cord, using the current clamp technique. In about half of the neurons the response properties were dominated by their ability to generate plateau potentials. In these cells the plateau potential could account for delayed onset of spiking and a phase of increasing spike frequency during depolarizing current pulses and for a depolarizing afterpotential following the stimulus. The cells usually received monosynaptic and polysynaptic input from the ipsilateral dorsal root and occasionally from the contralateral root. The plateau potential was insensitive to tetrodotoxin but blocked by nifedipine and by replacing Ca2+ with Co2+ in the medium. It is concluded that the response properties of neurons in the ventral horn outside the motor nucleus have differentiated response properties that may well contribute to spinal motor function.
Adult Rat Dorsal Root Ganglion Neurons Extend Neurites on Predegenerated But Not on Normal Peripheral Nerves In Vitro
Authors: Bedi Kuldip S. , Winter Janet , Berry Martin , Cohen James 
Published: April 2006

AbstractThe abilities of embryonic and adult rat sensory neurons to regenerate were compared when cultured on cryostat sections of normal and lesioned sciatic nerve tissues. Differences in neurite growth, visualized by GAP‐43 immunolabelling, were most pronounced on substrata consisting of longitudinal sections of normal versus predegenerated sciatic nerve. Adult dorsal root ganglion (DRG) neurons grew only on the lesioned nerves. Neurites extended along these sections in a characteristically longitudinal orientation, and this growth was not dependent on nerve growth factor. Embryonic DRG neurons extended neurites on sections from both types of nerves. These results highlight important differences in the regenerative abilities of embryonic and adult DRG neurons when grown on physiologically appropriate substrata.
L1 Cell Adhesion Molecule is Expressed by Noradrenergic but not Adrenergic Chromaffin Cells: A Possible Major Role for L1 in Adrenal Medullary Design
Authors: Léon Catherine , Grant Nancy , Aunis Dominique , Langley Keith 
Published: April 2006

AbstractThe adrenal medulla of higher animals is constituted of homotypic groups of chromaffin cells secreting either adrenalin or noradrenalin. Since not all chromaffin cells are individually innervated by fibres of the splanchnic nerve, this tissue characteristic is crucial to the physiological function of the gland. In an attempt to analyse differences between these chromaffin cell types which might underlie the establishment of this tissue pattern, we examined the expression of the adhesion molecule L1 in this gland by immunocytochemistry at the optical and ultrastructural levels in rats. L1, an adhesion molecule abundant in the central nervous system, was found to be present in the adrenal medulla of adults; it was strongly expressed on innervating axons and their surrounding Schwann cells and also on a subpopulation of chromaffin cells. The nature of these chromaffin cells was examined by immunocytochemistry using antibodies against the catecholamine‐synthesizing enzyme phenylethanolamine N‐methyltransferase (PNMT), which are capable of distinguishing between adrenergic and noradrenergic cells. Immunofluorescence labelling of sequential frozen sections demonstrated that chromaffin cells which express L1 do not express PNMT; conversely, L1 was not detected in any chromaffin cells expressing PNMT. Ultrastructural immunocytochemistry confirmed the existence of two non‐overlapping populations of chromaffin cells. It is concluded that, in the adrenal medulla, noradrenergic but not adrenergic chromaffin cells express this adhesion molecule. These data, together with our previous observations that all chromaffin cells express the neural cell adhesion molecule, NCAM, suggest that L1, in cooperation with NCAM, could be responsible for the association of noradrenergic cells in the form of homotypic aggregates segregated from groups of adrenergic cells within the adrenal medulla.
A Hidden Retinal Regenerative Capacity from the C Ciliary Margin is Reactivated In Vitro, that is Accompanied by Down‐regulation of Butyrylcholinesterase
Authors: Willbold Elmar , Layer Paul G. 
Published: April 2006

AbstractThe chicken retina has a capacity to regenerate in vivo, which is restricted up to embryonic day 4 (E4). Here we test the proliferative patterns of dissociated chicken cells from the centre retina or the ciliary margin, including pigmented cells, after their transfer into rotation culture. For central cells in culture, the uptake of [3H]thymidine after a short initial rise decreases similarly to their in ovo counterparts. In contrast, marginal cells that have been shown to regenerate up to E9 into retinotypic stratospheroids re‐enter a novel and long‐lasting phase of in vitro cell division. We have shown previously that cell types of all nuclear layers are produced. Both observations taken together indicate a pronounced self‐renewal of multipotent stem cells. Molecularly, the enzyme butyrylcholinesterase, which in other systems has been shown to mark transitory neuronal cells between proliferation and differentiation, is strongly expressed at the ciliary margin over most of the embryonic period. After these cells are transferred into rotation culture, butyrylcholinesterase is down‐regulated. Concomitantly, the neuronal differentiation marker acetylcholinesterase increases. We conclude that the regenerative capacity of the chick retina is not lost at E4, but rather remains hidden in the chicken ciliary margin, since it can be reactivated In vitro at least up to E9. We suggest that butyrylcholinesterase may be linked to the regulation of stem cell activity.