bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depolarization regulates cyclin D1 degradation and neuronal apoptosis: a hypothesis about the role of the ubiquitin/proteasome signalling pathway
Authors: Boutillier Anne‐Laurence , Kienlen‐Campard Pascal , Loeffler Jean‐Philippe 
Published: March 2003

AbstractDepolarization and subsequent calcium entry exert essential neuroprotective effects but the ultimate effector by which calcium blocks apoptosis is not known. Here we show that inhibition of calcium entry into cerebellar neurons by switching from high to low extracellular K+ concentrations (30–5 mm) induces apoptosis, that correlates with a rapid accumulation of cyclin D1 (CD1), an early marker of the G1/S transition of the cell cycle. These effects on apoptosis and cyclin D1 are mimicked either by blocking calcium entry into neurons (LaCl3, 100 μm or nifedipine, 10–6 m) or by inhibiting the calcium/calmodulin pathway (calmidazolium, 10–7 m). The increased CD1 protein levels do not result from a transcriptional upregulation of the CD1 gene by the Ca2+/calmodulin pathway but rather reflect an accumulation due to the lack of degradation by the proteasome‐dependent pathway. Specific proteasome antagonists: carbobenzoxyl‐leucinyl‐leucinyl‐norvalinal‐H (MG‐115), carbobenzoxyl‐leucinyl‐leucinyl‐leucinal‐H (MG‐132) and clasto‐lactacystin β‐lactone, induce neuronal apoptosis by themselves. Finally, this pathway is functional only at neuroprotective concentrations of K+ (30 mm), suggesting that calcium/CamK signalling pathway may regulate neuronal death by regulating the proteasome‐mediated degradation activity of rapidly turning‐over proteins (constitutively expressed genes or pre‐existing pools of mRNA).
Effect of catecholamines on the hyperpolarization‐activated cationic Ih and the inwardly rectifying potassium IKir currents in the rat substantia nigra pars compacta
Authors: Cathala L. , Paupardin‐Tritsch D. 
Published: March 2003

AbstractWhole‐cell ruptured‐patch and perforated‐patch recordings were used in principal neurons of the rat substantia nigra pars compacta (SNc) to study the effect of catecholamines both on the hyperpolarization‐activated cationic (Ih) and the inwardly rectifying potassium (IKir) currents. In internal potassium, a 2 min bath application of noradrenaline (NA; 50 μm) or dopamine (DA; 50 μm) both inhibited Ih and induced an outward current associated with an increase in IKir conductance. These two effects recovered poorly after wash‐out. Protein kinase A (PKA), protein kinase C (PKC) and phosphatases 1 and 2A inhibitors did not modify the NA and DA effects on the amplitude of Ih and IKir currents. They also had no effect on the recovery of the catecholamine responses. In perforated‐patch experiments, NA and DA also induced an inhibition of Ih and revealed an outward current associated with an increase in conductance. However, both effects recovered in less than 5 min following the wash‐out. These results indicate that neither PKA, PKC, nor phosphatases 1 or 2A were required in the NA and DA modulation of these two currents and that an intracellular factor, that could be either washed‐out or inversely up‐regulated in the ruptured‐patch configuration, was implicated in the recovery of both effects. In the presence of external barium (300 μm) or internal caesium which both blocked the outward current and the increase in conductance, neither NA nor DA affected Ih, suggesting that the effect on Ih observed is secondary to the activation of the IKir channels. Increasing chloride conductance of the cell by activation of GABAA receptors also induced an inhibition of Ih. All together these results suggest that the NA or DA induced inhibition of Ih could result from an occlusion of Ih by a space‐clamp effect.
Distribution of histamine H3‐receptor binding in the normal human basal ganglia: comparison with Huntington's and Parkinson's disease cases
Authors: Goodchild R. E. , Court J. A. , Hobson I. , Piggott M. A. , Perry R. H. , Ince P. , Jaros E. , Perry E. K. 
Published: March 2003

AbstractIt is now widely recognized that histamine acts as a neurotransmitter in the mammalian central nervous system. Three selective histamine receptors have been described, all of which are present in the basal ganglia. This study is a detailed, quantitative, autoradiographical examination of the densities of histamine H3‐receptors in coronal sections of human basal ganglia, using the selective ligand [3H]‐(R)‐α‐methylhistamine. [3H]‐(R)‐α‐methylhistamine binding was highest within the external and internal segments of the globus pallidus together with the substantia nigra. High levels were also found in the striatum, where density was significantly higher (P < 0.05) at a pre‐, as opposed to post‐, anterior commissure coronal level. Within the striatum, binding was noticeably higher in both the nucleus accumbens and acetylcholinesterase‐deficient striosomes, while being undetectable in the subthalamic nucleus and very low in both the ventroanterior and ventrolateral thalamic nuclei. An intermediate level of binding, often with a laminar distribution, was seen in the insular cortex. [3H]‐(R)‐α‐methylhistamine binding was also examined in both Parkinson's disease and Huntington's disease. No difference from control receptor density was found in any area examined in Parkinson's disease, while values were significantly lower in caudate (P < 0.001), putamen (P < 0.001), external (P < 0.001) and internal (P < 0.05) globus pallidus, although not the insular cortex, in Huntington's disease cases. These data suggest that H3‐receptors are present upon striatonigral projection neurons of the direct and indirect movement pathways thus providing histaminergic control over the activity of both these circuits.
The protein kinase C (PKC) substrate GAP‐43 is already expressed in neural precursor cells, colocalizes with PKCη and binds calmodulin
Authors: Esdar Christina , Oehrlein Silke A. , Reinhardt Sigrid , Maelicke Alfred , Herget Thomas 
Published: March 2003

AbstractExpression of the growth‐associated protein of 43‐kDa (GAP‐43), which is described as a postmitotic, neuron‐specific major protein kinase C (PKC) substrate, was investigated in the murine embryonic carcinoma cell line PCC7‐Mz1 which develops into a brain‐tissue‐like pattern of neuronal, fibroblast‐like and astroglial cells upon stimulation with all‐trans retinoic acid (RA). GAP‐43 expression was very low in stem cells, but increased on mRNA and protein level within the 12 h after differentiation was initiated. While the P1 promoter of the GAP‐43 gene gave rise to a 1.6‐kb mRNA and was already active at a very low level in PCC7‐Mz1 stem cells, transcription of the P2 promoter, which resulted in a 1.4‐kb mRNA, was completely blocked in stem cells but increased rapidly after RA treatment.Within the first 2 days of neural differentiation, GAP‐43 was localized with the cytoplasmic membrane and the Golgi complex of proliferating neural precursor cells. Then, GAP‐43 was translocated to the growth cones and neurites, and from day 6, when neurons began to acquire polarity, the protein was found in the axons. GAP‐43 was never detected in the non‐neuronal PCC7‐Mz1 derivatives, i.e. in fibroblasts or glial cells.In the foetal rat brain (prenatal day F11), GAP‐43 was expressed in the optic stalk, the lense plakode and in the postmitotic neurons of the marginal zone of the hindbrain. Moreover, in a layer between the ventricular and marginal zone of the hindbrain (F13) and forebrain (F15), GAP‐43 was already expressed in mitotic neural precursor cells.In PCC7‐Mz1 cultures, 2 days after addition of RA, GAP‐43 became phosphorylated upon activation of PKC, and colocalized specifically with the novel PKC isoform η. Phosphorylation of GAP‐43 caused a disruption of its complex with calmodulin. These data demonstrate that GAP‐43 is already a functional PKC substrate in prolific neuronal precursor cells, and may participate in neuronal cell lineage determination.
Proteolytic processing, axonal transport and differential distribution of chromogranins A and B, and secretogranin II (secretoneurin) in rat sciatic nerve and spinal cord
Authors: Li Jia‐Yi , Leitner Bernd , Lovisetti‐Scamihorn Paola , Winkler Hans , Dahlström Annica 
Published: March 2003

AbstractThe chromogranin family comprises chromogranin A and B, and secretogranin II. The present study has focused on the axonal transport of chromogranins/secretogranin II and their detailed distribution in peripheral nerves and the spinal cord. With radioimmunoassay (RIA) and column chromatography, we first studied the processing of chromogranin B and secretogranin II during axonal transport. No larger precursors of these peptides were detected in the sciatic nerves, indicating that they are already processed to a high degree early during axonal transport. We also analysed nerve segments above and below a crush, using RIA, in order to compare these accumulation data with those obtained by the cytofluorimetric‐scanning (CFS) technique. For the latter technique, the amounts of accumulation distal to the crush (presumably representing recycling and retrogradely transported peptides) were 30–40% of the amounts in the proximal accumulation for chromogranin A and secretoneurin, in contrast to chromogranin B, which showed 15% recycling. With the RIA, the corresponding values for secretoneurin and PE‐11 (antibody against chromogranin B) were 42% and 14%, respectively. Therefore, the data obtained by CFS were in excellent agreement with those obtained by RIA. In crushed sciatic nerves, chromogranin A was present in large axons as well as in small‐ and medium‐sized axons. Chromogranin B was mainly restricted to large axons, while secretoneurin was localized to bundles of small axons. This differential distribution was also found in the spinal roots and in the peripheral terminals. Chromogranin A was present in both ventral and dorsal roots, and chromogranin B was detected in ventral roots and in large sensory axons in the dorsal roots. Secretoneurin was dominant in the dorsal root. Double‐labelling studies with antibodies against choline acetyltransferase/vesicular acetylcholine transporter, or against tyrosine hydroxylase, confirmed that chromogranin A was distributed in cholinergic, sensory, as well as adrenergic neurons. Chromogranin B was mainly present in cholinergic motor neurons and large sensory neurons, and secretoneurin was restricted to adrenergic and sensory neurons. The present study demonstrates that chromogranins A and B, and secretoneurin are transported with fast axonal transport in the peripheral nerves, with different amounts of recycling, and that they are differentially distributed in different types of neurons in the peripheral nervous system and the spinal cord, suggesting that each of them may play a special role in subsets of neurons.
Heparan sulphate and HB‐GAM (heparin‐binding rowth‐associated molecule) in the development of the thalamocortical pathway of rat brain
Authors: Kinnunen Anu , Niemi Maria , Kinnunen Tarja , Kaksonen Marko , Nolo Riitta , Rauvala Heikki 
Published: March 2003

AbstractExtracellular matrix (ECM) molecules, such as laminin, tenascin, chondroitin sulphate proteoglycans and heparan sulphate proteoglycans have been suggested to have ‘signpost’ and directing roles in the formation of axonal projections in cortical development. We show here that the expression of the neurite outgrowth‐promoting protein heparin‐binding growth‐associated molecule (HB‐GAM) and N‐syndecan, a transmembrane heparan sulphate proteoglycan previously isolated as a receptor for HB‐GAM, is spatiotemporally associated with the developing thalamocortical pathway in the rat brain. Using in situ hybridization, thalamic neurons were shown to express mRNA for N‐syndecan, and in vitro, thalamic neurons grew more neurites on HB‐GAM than on laminin. The HB‐GAM‐induced neurite outgrowth in thalamic neurons was inhibited by heparitinase, heparin, soluble N‐syndecan and by an excess of soluble HB‐GAM in the culture medium. In a pathway assay, thalamic neurons selectively preferred attaching and growing neurites on matrices containing HB‐GAM than on those containing fibronectin or laminin alone, suggesting that HB‐GAM may modulate the effect of other ECM proteins. On an unfixed brain slice preparation, thalamic neurons repeatedly showed a typical neurite outgrowth and attachment pattern resembling the expression pattern of HB‐GAM. On the brain slices, the neurite outgrowth was significantly inhibited by heparitinase, heparin and soluble HB‐GAM, thus displaying features of neurite outgrowth on matrix‐bound HB‐GAM. Our results suggest that HB‐GAM is important for the neurite outgrowth of thalamic neurons and it may function as an ECM‐bound guidance cue for thalamic neurons that possess HB‐GAM‐binding heparan sulphates on their cell membrane.
Stability and plasticity of primary afferent projections following nerve regeneration and central degeneration
Authors: Belyantseva Inna A. , Lewin Gary R. 
Published: March 2003

AbstractSensory neurons of the dorsal root ganglia (DRG) regenerate their peripheral axons with relative ease following a nerve lesion. The capacity for central regeneration appears more limited. However, after nerve lesion, some DRG neurons gain a regenerative advantage to sprout centrally. We developed a lesion model in the rat to test whether, after prior lesion of their peripheral axons, subsets of cutaneous afferents benefit differently in their ability to sprout into adjacent spinal segments denervated by dorsal rhizotomy. We found that under identical circumstances, myelinated sensory neurons, small‐diameter peptidergic sensory neurons containing calcitonin gene related peptide (CGRP), and small‐diameter nonpeptidergic neurons that bind the lectin from the plant Griffonia simplificolia, isolectin B4 (IB4) differ dramatically in their ability to regenerate centrally. Myelinated afferent terminals labelled transganglionically with cholera‐toxin β‐subunit gain a small advantage in collaterally sprouting into the adjacent denervated neuropil in lamina III after prior peripheral nerve lesion. This central regenerative response was not mimicked by experimentally induced inflammation of sensory neuron cell bodies. Intact and unlesioned sensory neurons positive for CGRP sprout vigorously into segments denervated by rhizotomy in a nonsomatotopic manner. In contrast, IB4‐positive sensory neurons maintain a somatotopic distribution centrally, which is not altered by prior nerve lesion. These data reveal a remarkably heterogeneous response to regeneration‐promoting stimuli amongst three different types of cutaneous sensory neurons. In particular, the divergent responses of peptidergic and nonpeptidergic sensory neurons suggests profound functional differences between these neurochemically distinct neurons.
Expression of unphosphorylated class III β‐tubulin isotype in neuroepithelial cells demonstrates neuroblast commitment and differentiation
Authors: Fanarraga M. L. , Avila J. , Zabala J. C. 
Published: March 2003

AbstractNeuronal microtubules have unique stability properties achieved through developmental regulation at the expression and post‐translational levels on tubulins and microtubule associated proteins. One of the most specialized tubulins specific for neurons is class‐III β‐tubulin (also known as β6‐tubulin). Both the upregulation and the post‐translational processing of class‐III β‐tubulin are believed to be essential throughout neuronal differentiation. The present investigation documents the temporal and spatial patterns of class‐III β‐tubulin expression throughout neurogenesis. For this study a novel polyclonal antiserum named U‐β6, specific to unphosphorylated class‐III β‐tubulin has been developed, characterized and compared with its commercial homologue TuJ‐1. Our experiments indicate that the two antibodies recognize different forms of class‐III β‐tubulin both in vitro and in vivo. Biochemical data revealed that U‐β6 bound unphosphorylated soluble class‐III β‐tubulin specifically, while TuJ‐1 recognized both the phosphorylated and unphosphorylated forms of the denatured protein. In vivo U‐β6 was associated with neurogenesis and labelled newly committed CNS and PNS neuroblasts expressing neuroepithelial cytoskeletal (nestin and vimentin) and surface markers (the anti‐ganglioside supernatant, A2B5 and the polysialic acid neural adhesion molecule, PSA‐NCAM), as well as differentiating neurons. These studies with U‐β6 illustrate three main developmental steps in the neuronal lineage: the commitment of neuroepithelial cells to the lineage (U‐β6 +ve/TuJ‐1 –ve cells); a differentiation stage (U‐β6 +ve/TuJ‐1 +ve cells); and, finally, neuronal maturation correlating with a drop in unphosphorylated class‐III β‐tubulin immunostaining levels. These investigations also conclude that U‐β6 is an earlier marker than TuJ‐1 for the neuronal lineage in vivo, and it is thus the earliest neuronal lineage marker known so far.
Specific expression of ezrin, a cytoskeletal‐membrane linker protein, in a subset of chick retinotectal and sensory projections
Authors: Takahashi Masakazu , Yamagata Masahito , Noda Masaharu 
Published: March 2003

AbstractLamina‐specific neuronal connections are a fundamental feature in many parts of the vertebrate central nervous system. In the chick, the optic tectum is the primary visual centre, and it has a multilaminated structure consisting of 15 laminae, of which only three or four receive retinal projections. Each of the retinorecipient laminae establishes synaptic connections selectively from one of a few subsets of retinal ganglion cells (RGCs). We have generated a series of monoclonal antibodies that appear to stain only one of the retinorecipient laminae. One of these, TB4, stained lamina F which receives inputs from a subpopulation of ≈ 10–20% of RGCs which express the presynaptic acetylcholine receptor β2‐subunit. TB4 recognized a single 79‐kDa protein on immunoblotting. cDNA cloning and immunochemical analysis revealed that the TB4 antigen molecule was ezrin, a cytoskeletal‐membrane linker molecule belonging to the ezrin‐radixin‐moesin family. Unilateral enucleation of the eye, both prior to and after the establishment of retinotectal projections, attenuated the lamina‐selective staining with TB4 in the contralateral tectum, suggesting that ezrin is anterogradely transported from RGCs to lamina F. Ezrin was thus expressed in a subset of RGCs that project to lamina F. Similar subset‐selective expression and resultant lamina‐selective distribution of ezrin were also observed in the lamina‐specific central projections from the dorsal root ganglia. The staining pattern with TB4 in the dorsal root ganglia and spinal cord indicated that high expression of ezrin was restricted in cutaneous sensory neurons, but not in muscle sensory neurons. Since ezrin modulates cell morphology and cell adhesion profiles by linking membrane proteins with the cytoskeleton, it was suggested that ezrin is involved in the formation and/or maintenance of lamina‐specific connections for neuronal subpopulations in the visual and somatosensory systems.
Do superior colliculus projection zones in the inferior pulvinar project to MT in primates?
Authors: Stepniewska Iwona , Qi Hui‐Xin , Kaas Jon H. 
Published: March 2003

AbstractIn order to determine the relationship of superior colliculus inputs to thalamic neurons projecting to the middle temporal visual area (MT), injections of wheat germ agglutinin conjugated with horseradish peroxidase were placed in the superior colliculus of three owl monkeys, with injections of Fast Blue in the MT. The locations of labelled terminals and neurons in the posterior thalamus were related to four architectonically distinct nuclei of the inferior pulvinar (Stepniewska & Kaas, Vis. Neurosci.14, pp.1043–1060, 1997). Fast Blue injections in the MT labelled neurons largely in the medial nucleus of the inferior pulvinar. A few labelled neurons were found in the adjoining central medial nucleus of the inferior pulvinar, as well as in the lateral pulvinar and the dorsal lateral geniculate nucleus. Superior colliculus inputs were most dense in the posterior and medial nuclei of the inferior pulvinar. There were sparser inputs to the central lateral nucleus of the inferior pulvinar, locations in the lateral and medial pulvinar, and the dorsal lateral geniculate nucleus. The results indicate that the medial nucleus of the inferior pulvinar, the major projection zone to the MT, does not receive a significant input from the superior colliculus.
Chronic morphine exposure and spontaneous withdrawal are associated with modifications of dopamine receptor and neuropeptide gene expression in the rat striatum
Authors: Georges François , Stinus Luis , Bloch Bertrand , Moine Catherine Le 
Published: March 2003

AbstractThe influence of chronic morphine and spontaneous withdrawal on the expression of dopamine receptors and neuropeptide genes in the rat striatum was investigated. Morphine dependence was induced by subcutaneous implantation of two morphine pellets for 6 days. Rats were made abstinent by removal of the pellets 1, 2 or 3 days before they were killed. The mRNA levels coding for D1‐ and D2‐dopamine receptors, dynorphin, preproenkephalin A and substance P were determined by quantitative in situ hybridization. The caudate putamen and the nucleus accumbens showed equivalent modifications in dopamine receptor and neuropeptide gene expression. After 6 days of morphine, a decrease in D2‐dopamine receptor and neuropeptide mRNA levels was observed (– 30%), but there was no change in D1‐dopamine receptor mRNA. In abstinent rats, both D1‐ and D2‐dopamine receptor mRNA levels were decreased 1 day after withdrawal (– 30% compared with chronic morphine). In contrast, neuropeptide mRNA levels were unaffected when compared with those observed after 6 days of morphine. During the second and third day of withdrawal, there was a gradual return to the levels seen in the placebo‐treated group, for both dopamine receptor and neuropeptide mRNAs. Phenotypical characterization of striatal neurons expressing μ and κ opioid receptor mRNAs showed that, in striatonigral neurons, both mRNAs were colocalized with D1‐receptor and Dyn mRNAs. Our results suggest that during morphine dependence, dopamine and morphine exert opposite effects on striatonigral neurons, and that effects occurring on striatopallidal neurons are under dopaminergic control. We also show that withdrawal is associated with a down regulation of the postsynaptic D1 and D2 receptors.