bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotype Specification of Cortical Neurons During a Period of Molecular Plasticity
Authors: Obst Kirstin , Wahle Petra 
Published: April 2006

AbstractThe transient expression of neuropeptide transmitters is a common feature of the developing cortex. We have now analysed the role of cortical afferents in shaping the neurochemical architecture of rat visual cortex using organotypic cultures. Deafferented cortex monocultures prepared from newborn rats reveal a constant NPY mRNA expression in 6–8% of all cortical neurons up to 90 days in vitro (DIV). In contrast, afferent thalamocortical and corticocortical axonal innervation elicits a progressive reduction in the percentage of NPY mRNA expressing neurons from initially 6–8% in 30DIV cocultures to 2–3% and 3–4% respectively in 60DIV cocultures, which is maintained for up to 90DIV. This phenotype restriction is not observed in only efferently connected corticocollicular cocultures. Further, axonal innervation does not change the percentage of GAD mRNA‐expressing neurons, which remains at 13% in mono‐ and cocultures. When feeding thalamocortical cocultures with monoculture‐conditioned medium between 3–20DIV followed by normal medium up to 60DIV, the phenotype restriction fails to occur in the cocultured cortex. We conclude that cortex‐derived factors secreted into the medium by a monoculture suppress the phenotype‐restricting capacity of the afferents, but only when present within the first 14DIV during the period of formation of axonal connections. To elucidate the nature of the cortex‐derived factors, brain‐derived neurotrophic factor was applied to the medium. When applied for the first 14DIV, it does not prevent the phenotype restriction from occurring. This suggests that epigenetic factors such as axonal innervation and cortex‐derived factors other than brain‐derived neurotrophic factor govern a phenotype decision in neocortical neurons during a period of molecular plasticity.
Learning Deficit in BDNF Mutant Mice
Authors: Linnarsson Sten , Björklund Anders , Ernfors Patrik 
Published: April 2006

AbstractBrain‐derived neurotrophic factor (BDNF) has been implicated in the regulation of high‐frequency synaptic transmission and long‐term potentiation in the hippocampus, processes that are also thought to be involved in the learning of spatial tasks such as the Morris water maze. In order to determine whether BDNF is required for normal spatial learning, mice carrying a deletion in one copy of the BDNF gene were subjected to the Morris water maze task. Young adult BDNF mutant mice were significantly impaired compared with wild‐type mice, requiring twice the number of days to reach full performance. Aged wild‐type mice performed significantly worse than young wild‐type mice and the effect was even more pronounced in the BDNF mutant mice, which did not learn at all. Although there was no difference in mean swimming speed between BDNF mutant and wild‐type mice, we cannot exclude the possibility that developmental or peripheral deficits also contribute to the learning deficits in these mice. In situ hybridization and RNase protection analysis revealed that BDNF mRNA expression was indeed decreased in BDNF mutant mice. Furthermore, a pronounced effect of age on BDNF mRNA expression was seen, displayed as both a reduced level of mRNA expression and a reduced or entirely absent layer‐specific expression pattern in the cerebral cortex of aged animals. Thus, our data suggest that BDNF expression may be linked to learning.
HERG‐ and IRK‐like Inward Rectifier Currents are Sequentially Expressed During Neuronal Development of Neural Crest Cells and their Derivatives
Authors: Arcangeli Annarosa , Rosati Barbara , Cherubini Alessia , Crociani Olivia , Fontana Lucrezia , Ziller Catherine , Wanke Enzo , Olivotto Massimo 
Published: April 2006

AbstractQuail neural crest cells were cultured in a differentiative medium to study the inward K+ channel profile in neuronal precursors at various stages of maturation. Between 12 and 24 h of culture, neural crest‐derived neurons displayed, in addition to the previously described outward depolarization‐activated K+ currents, an inward current enhanced in high K+ medium. A biophysical and pharmacological analysis led us to conclude that this inward K+ current is identical to that previously demonstrated in mouse and human neuroblastoma cell lines (IIR). This current (quail IIR or qllR), which is active at membrane potentials positive to ‐35 mV, was blocked by Cs+ and by class Ill antiarrhythmic drugs, thus resembling the K+ current encoded by the human ether‐a‐go‐go‐related gene (HERG). At later stages of incubation (>48 h), neural crest‐derived neurons underwent morphological and biochemical differentiation and expressed fast Na+ currents. At this stage the cells lost qllR, displaying instead a classical inward rectifier K+ (IRK) current (quail IIRK= qIIRK). This substitution was reflected in the resting potential (VREST), which became hyperpolarized by >20 mV compared with the 24 h cells. Neurons were also harvested from peripheral ganglia and other derivatives originating from the migration of neural crest cells, viz. ciliary ganglia, dorsal root ganglia, adrenal medulla and sympathetic chain ganglia. After brief culture following harvesting from young embryos, ganglionic neurons always expressed qilR. On the other hand, when ganglia were explanted from older embryos (7–12 days), briefly cultured neurons displayed the IRK‐like current. Again, in all the above derivatives the qllR substitution by qllRK was accompanied by a 20 mV hyperpolarization of VREST. Together, these data indicate that the VREST of normal neuronal precursors is sequentially regulated by HERG‐ and IRK‐like currents, suggesting that HERG‐like channels mark an immature and transient stage of neuronal differentiation, probably the same stage frozen in neuroblastomas by neoplastic transformation.
Evidence from Confocal Fluorescence Microscopy for a Dense, Reciprocal Innervation Between AVP‐,somatostatin‐, VIP/PHI‐, GRP‐ and VIP/PHI/GRP‐immunoreactive Neurons in the Rat Suprachiasmatic Nucleus
Authors: Romijn H. J. , Sluiter A. A. , Pool C. W. , Wortel J. , Buijs R. M. 
Published: April 2006

AbstractThe rat suprachiasmatic nucleus (SCN) consists of several classes of neurons which can be identified by their transmitter content. Knowledge of putative interaction between these different cell types is essential in order to understand the possibilities of information processing within the SCN. The aim of the present study was therefore to obtain more information about the mutual innervation between the main cell classes in the rat SCN, viz. those containing the neuropeptides arginine vasopressin (AVP), vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), gastrin‐releasing peptide (GRP) and somatostatin respectively. For this purpose, vibratome sections were double‐immunolabelled for seven different peptide combinations and subsequently analysed by high‐resolution confocal laser scanning fluorescence microscopy. Attention was focused on axosomatic appositions, the occurrence and frequency of which were quantitatively estimated. Our analysis of double‐immunolabelled sections demonstrated that some of the VIP‐ and some of the GRP‐immunoreactive nerve cells and endings showed colocalization. Assuming, on the basis of literature data, that VIP and PHI are always colocalized at the cellular level, the five main cell classes in the SCN appeared to be interconnected, at least axosomatically, in the following reciprocal way: AVP ↔ VIP/PHI, AVP ↔ GRP, AVP ↔ somatostatin, somatostatin ↔ VIP/PHI, somatostatin ↔ GRP, VIP/PHI ↔ GRP, VIP/PHI/GRP ↔ GRP, VIP/PHI/GRP ↔ VIP/ PHI. In addition to this heterologous axosomatic innervation, these cell groups also showed substantial homologous innervation. Supported by electron microscope data from the literature showing the existence of axodendritic synapses for some of these peptide combinations, our findings strongly suggest that the rat SCN comprises a complex synaptic network with strong interactive capabilities, which is probably a requisite for its biological clock function.
Pronase Acutely Modifies High Voltage‐activated Calcium Currents and Cell Properties of Lymnaea Neurons
Authors: Hermann P. M. , Lukowiak K. , Wildering W. C. , Bulloch A. G. M. 
Published: April 2006

AbstractPronase E (‘pronase’) is one of the proteolytic enzymes that are used in preparative procedures such as cell isolation and to soften the sheath of invertebrate ganglia. Although several effects of proteolytic enzymes on the physiology of non‐neuronal tissues have been described, the effects of these enzymes on central neurons have received little attention. We examined the effects of bath‐applied pronase on neurons in the Lymnaea central nervous system and in vitro. Pronase caused action potential broadening in neurons that exhibit a shoulder on the repolarization phase of their action potentials. This effect of pronase was accompanied by, although unrelated to, a depolarization and decrease in action potential interval. Some, but not all, effects of pronase in the central nervous system were reversible. For example, the decreases in membrane potential and action potential interval were both reversed after ∼1 h of washing with saline. However, the effect of pronase on the action potential duration was not reversed after a period of 90 min. The modulation of action potential width prompted us to examine Ca2+ currents. Exposure to pronase resulted in an increase in both peak and late high voltage‐activated Ca2+ currents in isolated neurons. Pronase neither changed the inactivation rate nor caused a shift in the current‐voltage relationship of the current. The changes in action potential duration could be prevented by application of 0.1 mM Cd2+, indicating that the action potential broadening caused by pronase depends on Ca2+ influx. This is the first systematic study of the acute and direct actions of pronase on Ca2+ currents and cell properties both in the CNS and in vitro.
The Role of the Mouse Macrophage Scavenger Receptor in Myelin Phagocytosis
Authors: da Costa Cristiane Cabral , van der Laan Luc J. W. , Dijkstra Christine D. , Brück Wolfgang 
Published: April 2006

AbstractMyelin phagocytosis during Wallerian degeneration and immune‐mediated demyelination depends on the action of mononuclear cells of the monocyte/macrophage system. The present study investigated the role of the macrophage scavenger receptor, a trimeric membrane glycoprotein, in myelin uptake by macrophages. Two in vitro models of myelin phagocytosis were used: an organ culture model of mouse peripheral nerves exposed to cocultured macrophages and a quantitative flow cytometric assay. Different concentrations of the monoclonal rat anti‐mouse scavenger receptor antibody (2F8) were applied to these systems to selectively block the macrophage scavenger receptor. Concentration‐dependent effects on macrophage migration and myelin uptake were seen when the macrophage scavenger receptor was blocked by the antibody 2F8. Low concentrations reduced myelin phagocytosis by the invading macrophages; higher concentrations completely abolished macrophage invasion of the nerves. Using a quantitative flow cytometric assay it was also shown that the 2F8 antibody inhibits phagocytosis of myelin in a dose‐dependent manner. These data indicate that the macrophage scavenger receptor is involved in myelin phagocytosis by macrophages.
Localization of Putative Receptors for Tetanus Toxin and Botulinum Neurotoxin Type A in Rat Central Nervous System
Authors: Herreros J. , Marti E. , Ruiz‐Montasell B. , Casanova A. , Niemann H. , Blasi J. 
Published: April 2006

AbstractClostridial neurotoxins (tetanus and botulinum toxins) are potent blockers of neurotransmitter release. These toxins act specifically on the nervous system by interacting with still non‐identified protein receptors together with gangliosides. Whereas many biochemical data are available on their binding properties to neuronal membranes in vitro, there is poor morphological evidence of their binding to mammalian central nervous system. In the present study, the binding of tetanus and botulinum neurotoxin type A to rat brain sections is reported. Both toxins bound to nerve terminals with a broad distribution in brain. Tetanus toxin additionally bound to nerve fibres. The staining patterns were clearly shown to be due to the interaction of the heavy chains, which contain the binding moiety, with the tissue. In an attempt to investigate the nature of the acceptors present in the tissue, some sections were pre‐incubated with periodic acid. This treatment resulted in the additional binding of botulinum neurotoxin type A to nerve fibres. Since the extended staining of nerve terminals was not modified by this pretreatment, it is suggested that protein receptors of clostridial neurotoxins are located at the nerve terminals, which may be common constituents of the synapses.
NMDA Receptor Activation Triggers Voltage Oscillations, Plateau Potentials and Burstinq in Neonatal Rat Lumbar Motoneurons ln Vitro
Authors: MacLean Jason N. , Schmidt Brian J. , Hochman Shawn 
Published: April 2006

AbstractWhole‐cell recordings of lumbar motoneurons in the intact neonatal rat spinal cord in vitro were undertaken to examine the effects of Kmethyl‐D‐aspartate (NMDA) receptor activation on membrane behaviour. Bath application of NMDA induced rhythmic voltage oscillations of 5.9 ± 2.1 mV (SD) at a frequency of 4.4 ± 1.5 Hz. Amplitude, but not frequency, of the voltage oscillations was membrane potential‐dependent. Voltage oscillations could recruit action potentials and/or plateau potentials with or without superimposed bursting. Blockade of synaptic transmission with tetrodotoxin (TTX) sometimes resulted in a loss of oscillatory activity which could then be restored by increasing the NMDA concentration. After application of TTX, the trajectory of NMDA‐induced oscillations was similar to the trajectory induced in the presence of intact synaptic networks, although the mean oscillation duration was longer and the oscillation frequency was slower (1.8 ± 1.1 Hz). Current ramps delivered after bath application of NMDA demonstrated bistable membrane properties which may underlie the plateau potentials. Injection of intracellular current pulses could initiate, entrain and terminate individual plateau potentials. The results suggest that membrane depolarization produced by oscillations may activate other intrinsic conductances which generate plateau potentials, thereby providing the neuron with enhanced voltage sensitivity, compared to that produced by NMDA receptor activation alone. These oscillatory events may have a role in the regulation of motor output in a variety of rhythmic behaviours including locomotion.
Phosphorylation‐dependent Effects of Synapsin IIa on Actin Polymerization and Network Formation
Authors: Nielander Hendrikus B. , Onofri Franco , Schaeffer Eric , Menegon Andrea , Fesce Riccardo , Valtorta Flavia , Greengard Paul , Benfenati Fabio 
Published: April 2006

AbstractThe synapsins are a family of synaptic vesicle phosphoproteins which play a key role in the regulation of neurotransmitter release and synapse formation. In the case of synapsin I, these biological properties have been attributed to its ability to interact with both synaptic vesicles and the actin‐based cytoskeleton. Although synapsin II shares some of the biological properties of synapsin I, much less is known of its molecular properties. We have investigated the interactions of recombinant rat synapsin Ila with monomeric and filamentous actin and the sensitivity of those interactions to phosphorylation, and found that: i) dephosphotylated synapsin II stimulates actin polymerization by binding to actin monomers and forming actively elongating nuclei and by facilitating the spontaneous nucleation/elongation processes; ii) dephosphorylated synapsin II induces the formation of thick and ordered bundles of actin filaments with greater potency than synapsin I; iii) phosphorylation by protein kinase A markedly inhibits the ability of synapsin II to interact with both actin monomers and filaments. The results indicate that the interactions of synapsin II with actin are similar but not identical to those of synapsin I and suggest that synapsin II may play a major structural role in mature and developing nerve terminals, which is only partially overlapping with the role played by synapsin I.
DeveIopmentalIy ReguIated Alternative SpIicing of mRNAs encoding N‐Terminal Tau Variants in the Rat Hippocampus: Structural and Functional Implications
Authors: Collet Joan , Fehrat Lotfi , Pollard Hélène , de Pouplana Lluis Ribas , Charton Gérard , Bernard Anne , Moreau Jo'lle , Ben‐Ari Yezekiel , Khrestchatisky Michel 
Published: April 2006

AbstractTau protein variants are axonal microtubule‐associated phosphoproteins whose expression correlates with developmentally regulated neurite outgrowth. A single gene encodes multiple tau transcripts via complex alternative splicing. We studied the expression of the mRNAs encoding N‐terminal variants of tau, and we showed distinct alternative splicing of exons 2 and 3 in nervous tissues of the adult rat, including the inner ear, hippocampus, cortex, striatum, brainstem, cerebellum, olfactory bulb and retina. Using the reverse transcriptase‐coupled polymerase chain reaction and in situ hybridization, we then focused our developmental study on hippocampal neurons, both in vivo and in vitro, to address the developmental and spatial expression of the alternatively spliced mRNAs encoding N‐terminal variants of tau. Tau mRNAs devoid of exons 2 and 3 were present throughout development, although their levels decreased in adults. Those containing exon 2 but not exon 3 were already present in the hippocampus of newborn rats and their levels increased during the first postnatal week, mainly in the pyramidal cell layer. Tau RNAs containing exons 2 and 3 appeared at the end of this period in the pyramidal cell layer and in the dentate granule cells. Exon 2‐containing mRNAs seemed to be associated with cells undergoing axonal sprouting, while exon 3‐containing RNAs were expressed in mature neurons that had established their connections. The timing and pattern of tau alternative splicing were maintained in cultured hippocampal neurons, suggesting that splicing processes are independent of the organized connectivity and of the environmental cues provided in vivo. Secondary structure predictions of tau variants revealed that the insertion of the exon 3‐encoded domain substantially modifies the secondary structure of the N‐terminal region of tau. This N‐terminal heterogeneity may confer distinct regulatory roles on the tau variants during ontogeny and may contribute to plasticity in the adult rat brain.
Rat Mature Sympathetic Neurones Derive Neurotrophin 3 from Peripheral Effector Tissues
Authors: Zhou Xin‐Fu , Chie Edward T. , Deng Yan‐Shen , Rush Robert A. 
Published: April 2006

AbstractIn a previous study we have demonstrated that endogenous neurotrophin 3 (NT3) is required for the survival of most sympathetic neurones in postnatal rats. However, the mechanisms underlying the action of NT3 on sympathetic neurones is not known. Neither is it understood whether NT3 is retrogradely transported from peripheral tissues or acts locally in an autocrine fashion. In the present study, NT3‐mRNA was quantified in sympathetic effector tissues and NT3 protein was localized in intact and lesioned sympathetic nerves in rats. NT3‐mRNA is expressed and developmentally regulated in many effector tissues including mesenteric arteries, salivary gland, heart and kidney but hardly detectable in the superior cervical ganglia of adult animals. The majority of sympathetic neurones express immunoreactivity for TrkA and TrkC in both neonatal and adult rats. Sympathetic somata are normally immunoreactive for NT3, but the immunoreactivity is abolished by systemic administration of NT3 antibodies or axotomy of postganglionic neurones, suggesting an accumulation of NT3 from extraneuronal sources. Furthermore, the detection of NT3‐immunoreactivity in the internal carotid nerve as early as 3 h following a compression and only on the distal side indicates endogenous NT3 is retrogradely transported by sympathetic neurones. These studies provide evidence indicating that NT3, like nerve growth factor, is an effector tissue‐derived neurotrophic factor for sympathetic neurones both during development and in the adult animal. Thus, we have provided a clear example that one type of neurone derives, through a retrograde transport mechanism, two neurotrophic factors simultaneously from its peripheral effector tissues.
Activation of gp 130 by IL‐6/soluble IL‐6 receptor induces neuronal differentiation
Authors: März Pia , Herget Thomas , Lang Elke , Otter Uwe , Rose‐John Stefan 
Published: April 2006

AbstractInterleukin‐6 (IL‐6) on target cells binds to the specific IL‐6 receptor (IL‐6R) and subsequently induces homodimerization of the signal‐transducing protein gpl30. Cells which express gpl30 but no IL‐6R and which therefore do not respond to IL‐6 can be stimulated by the complex of IL‐6 and soluble IL‐6R (slL‐6R). Here we show that on rat pheochromocytoma cells (PC12), the combination of IL‐6 and slL‐6R but not IL‐6 alone induces expression of c‐fos, GAP‐43 and neuron‐specific enolase followed by neuron‐specific differentiation and formation of a neuronal network. The differentiation was dose‐and time‐dependent and followed the same kinetics as nerve‐growth factor (NGF)‐induced differentiation. The responses of PC12 cells to IL‐6/slL‐6R and NGF were additive, suggesting independent signaling pathways. We demonstrate that activation of gpl30 generates a neuronal differentiation signal that is equivalent to and independent of trk/NGF receptor tyrosine kinase. Interestingly, the failure of IL‐6 to induce differentiation of PC12 cells is not due to lack of surface expression of IL‐6R as IL‐6 alone triggered expression of GAP‐43 mRNA and protein. We hypothesize that PC12 cells express more gp130 than IL‐6R and that the extent of activated gp130 molecules determines the quality of the response.
Effects of Neurotransplants and BDNF on the Survival and Regeneration of Injured Adult Spinal Motoneurons
Authors: Novikova Lioudmila , Novikov Lev , Kellerth Jan‐Olof 
Published: April 2006

AbstractWe compared the effects of peripheral nerve grafts, embryonic spinal cord transplants and brain‐derived neurotrophic factor (BDNF) on the survival and axon regeneration of adult rat spinal motor neurons undergoing retrograde degeneration after ventral root avulsion. Following implantation into the dorsolateral funiculus of the injured spinal cord segment, neither a peripheral nerve graft nor a combination of peripheral nerve graft with embryonic spinal cord transplant could prevent the retrograde motor neuron degeneration induced by ventral root avulsion. However, intrathecal infusion of BDNF promoted long‐term survival of the lesioned motor neurons and induced abundant motor axon regeneration from the avulsion zone along the spinal cord surface towards the BDNF source. A combination of ventral root reconstitution and BDNF treatment might therefore be a promising means for the support of both motor neuron survival and guided motor axon regeneration after ventral root lesions.