bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal axonal physiology is associated with altered expression and distribution of Kv1.1 and Kv1.2 K+ channels after chronic spinal cord injury
Authors: Nashmi Raad , Jones Owen T. , Fehlings Michael G. 
Published: March 2003

AbstractDysfunction of surviving axons which traverse the site of spinal cord injury (SCI) has been linked to altered sensitivity to the K+ channel blocker 4‐aminopyridine (4‐AP) and appears to contribute to post‐traumatic neurological deficits although the underlying mechanisms remain unclear. In this study, sucrose gap electrophysiology in isolated dorsal column strips, Western blotting and confocal immunofluorescence microscopy were used to identify the K+ channels associated with axonal dysfunction after chronic (6–8 weeks postinjury) clip compresssion SCI of the thoracic cord at T7 in rats. The K+ channel blockers 4‐AP (200 μm, 1 mm and 10 mm) and α‐dendrotoxin (α‐DTX, 500 nm) resulted in a significant relative increase in the amplitude and area of compound action potentials (CAP) recorded from chronically injured dorsal column axons in comparison with control noninjured preparations. In contrast, TEA (10 mm) and CsCl (2 mm) had similar effects on injured and control spinal cord axons. Western blotting and quantitative immunofluorescence microscopy showed increased expression of Kv1.1 and Kv1.2 K+ channel proteins on spinal cord axons following injury. In addition, Kv1.1 and Kv1.2 showed a dispersed staining pattern along injured axons in contrast to a paired juxtaparanodal localization in uninjured spinal cord axons. Furthermore, labelled α‐DTX colocalized with Kv1.1 and Kv1.2 along axons. These findings suggest a novel mechanism of axonal dysfunction after SCI whereby an increased 4‐AP‐ and α‐DTX‐sensitive K+ conductance, mediated in part by increased Kv1.1 and Kv1.2 K+ channel expression, contributes to abnormal axonal physiology in surviving axons.
NO‐mediated cGMP synthesis in cholinergic neurons in the rat forebrain: effects of lesioning dopaminergic or serotonergic pathways on nNOS and cGMP synthesis
Authors: De Vente J. , Van Ittersum M. Markerink‐. , Van Abeelen J. , Emson P. C. , Axer H. , Steinbusch H. W. M. 
Published: March 2003

AbstractNitric oxide synthase (NOS) activity and NO‐mediated cGMP synthesis were studied in the rat forebrain of control animals and animals which had received a unilateral lesioning of dopaminergic or serotonergic pathways. Lesioning of the dopaminergic innervation using 6‐hydroxydopamine resulted in a 50% decrease in NOS activity in the lesioned frontal cortex and caudate putamen. Lesioning of the serotonergic innervation using 5,7‐dihydroxytryptamine had no effect on NOS activity. NO‐mediated cGMP accumulation in rat forebrain slices was not affected by 6‐hydroxydopamine or 5,7,‐dihydroxytryptamine lesioning. Using cGMP immunocytochemistry, it was demonstrated that NO‐mediated cGMP synthesis was absent from dopaminergic, serotonergic, GABA‐ergic and neuronal NOS‐containing nerve fibres. A minor colocalization of cGMP immunoreactivity was found in parvalbumin‐containing fibres in the cortex. Extensive colocalization between cGMP immunoreactivity and the acetylcholine transporter was found in all cortical areas and in the caudate putamen. There was no effect of the lesions on this colocalization. These results demonstrate NO‐mediated cGMP accumulation in cholinergic fibres in the forebrain of the rat and suggest an anterograde signalling function of NO in cholinergic neuronal systems in the cortex and caudate putamen of the rat.
Hyperpolarization‐activated current, Ih, in inspiratory brainstem neurons and its inhibition by hypoxia
Authors: Mironov S. L. , Langohr K. , Richter D. W. 
Published: March 2003

AbstractA hyperpolarization‐activated current, Ih, is often implied in pacemaker‐like depolarizations during rhythmic oscillatory activity. We describe Ih in the isolated respiratory centre of immature mice (P6–P11). Ih was recorded in 15% (22/146) of all inspiratory neurons examined. The mean half‐maximal Ih activation occurred at −78 mV and the reversal potential was −40 mV. Ih was inhibited by Cs+ (1–5 mm) and by organic blockers N‐ethyl‐1,6‐dihydro‐1,2‐dimethyl‐6‐(methylimino)‐N‐phenyl‐4‐pyrimidinamine (ZD 7288; 0.3–3 μm) and N,N′‐bis‐(3,4‐dimethylphenylethyl)‐N‐methylamine (YS 035, 3–30 μm), but not by Ba2+ (0.5 mm). The organic Ih blockers did not change the inspiratory bursts recorded from the XIIth nerve and synaptic drives in inspiratory neurons. Hypoxia reversibly inhibited Ih but, in the presence of organic blockers, the hypoxic reaction remained unchanged. We conclude that although Ih channels are functional in a minority of inspiratory neurons, Ih does not contribute to respiratory rhythm generation or its modulation by hypoxia.
Reduction of stress‐induced analgesia but not of exogenous opioid effects in mice lacking CB1 receptors
Authors: Valverde Olga , Ledent Catherine , Beslot Francoise , Parmentier Marc , Roques Bernard P. 
Published: March 2003

AbstractCB1 cannabinoid receptors are widely distributed in the central nervous system where they mediate most of the cannabinoid‐induced responses. Here we have evaluated the interactions between the CB1 cannabinoid receptors and the endogenous opioid system by assaying a number of well‐characterized opioid responses, e.g. antinociception and stress‐mediated effects, on mutant mice in which the CB1 receptor gene was invalidated. The spontaneous responses to various nociceptive stimuli (thermal, mechanical and visceral pain) were not changed in mutant CB1 mice. Furthermore, the absence of the CB1 cannabinoid receptor did not modify the antinociceptive effects induced by different opioid agonists: morphine (preferential mu opioid agonist), d‐Pen2‐d‐Pen5‐enkephalin (DPDPE) and deltorphin II (selective delta opioid agonists), and U‐50,488H (selective kappa opioid agonist) in the hot‐plate and tail‐immersion tests. In contrast, the stress‐induced opioid mediated responses were modified in CB1 mutants. Indeed, these mutants did not exhibit antinociception following a forced swim in water at 34 °C and presented a decrease in the immobility induced by the previous exposure to electric footshock. However, the antinociception induced by a forced swim in water at 10 °C was preserved in CB1 mutants. These results indicate that CB1 receptors are not involved in the antinociceptive responses to exogenous opioids, but that a physiological interaction between the opioid and cannabinoid systems is necessary to allow the development of opioid‐mediated responses to stress.
Connective tissue growth factor: a novel player in tissue reorganization after brain injury?
Authors: Hertel Moritz , Tretter Yvonne , Alzheimer Christian , Werner Sabine 
Published: March 2003

AbstractRecent studies have suggested a role of connective tissue growth factor (CTGF) in repair processes of the skin as well as in various types of fibrotic disease. However, a function of this molecule in central nervous system (CNS) repair has not been demonstrated yet. In this study we analysed the temporal and spatial expression pattern of CTGF after unilateral kainic acid lesions of the hippocampal CA3 region in mice. We found a strong induction of CTGF mRNA and protein expression in neurons and glial cells of the lesioned hippocampus. Interestingly, increased expression of this mitogen was accompanied by elevated levels of the extracellular matrix molecule fibronectin, which is a known target of CTGF action. Therefore, our data indicate a novel function of CTGF in postlesional restructuring of the hippocampus, where it possibly participates in glial scar formation.
Dynamics of munc18‐1 phosphorylation/dephosphorylation in rat brain nerve terminals
Authors: De Vries Klaas Jan , Geijtenbeek Arwin , Brian Elisabeth C. , De Graan Pierre N. E. , Ghijsen Wim E. J. M. , Verhage Matthijs 
Published: March 2003

AbstractMunc18‐1 is a mammalian member of the SEC1 protein family implicated in neuronal secretion. Its sequence contains several consensus sites for phosphorylation by protein kinase C (PKC), a kinase known to enhance secretion. We have characterized the phosphorylation of the synaptic munc18‐1 pool by endogenous, presynaptic PKC‐isoforms. In isolated rat brain nerve terminals, munc18‐1 was almost completely nonphosphorylated. Its phosphorylation state increased by 250% on inhibition of endogenous phosphatases and by 1500% on additional, direct PKC activation using phorbol esters. K+‐evoked depolarization also increased munc18‐1 phosphorylation, by 50% within 5 s in a Ca2+‐dependent manner. Munc18‐1 phosphorylation in nerve terminals was blocked by PKC inhibitors. Activation of endogenous PKC in nerve terminals inhibited the interaction of synaptic munc18‐1 with its binding partner syntaxin‐1A by 50%. Munc18‐1 antisera precipitated 80% of native, brain‐derived munc18‐1 from salt solutions, but only 12% from synaptosomal lysates, together with 6% synaptic syntaxin‐1A/B; these amounts were not changed by PKC activation. In this 12%, the phosphate incorporation per mole of munc18 was four‐fold lower than the total pool. We conclude that the synaptic munc18‐1 pool can be readily and rapidly phosphorylated by endogenous presynaptic PKC isoforms. A high constitutive phosphatase activity keeps its basal phosphorylation state low so that PKC activation can increase the phosphorylation state dramatically. These phosphorylation dynamics and the effects on the interaction with syntaxin‐1A make munc18‐1 a prominent candidate to account for PKC‐dependent enhancement of secretion.
Serotonin may stimulate granule cell proliferation in the adult hippocampus, as observed in rats grafted with foetal raphe neurons
Authors: Brezun Jean Michel , Daszuta Annie 
Published: March 2003

AbstractThe long‐term effects of hippocampal serotonergic denervation and reinnervation by foetal raphe tissue were examined in the dentate gyrus where neurons are continously born in the adult. Complete lesion of serotonin neurons following injections of 5,7‐dihydroxytryptamine in the dorsal and medial raphe nuclei produced long‐term decreases in the number of newly generated granule cells identified with 5‐Bromo‐2′‐deoxyuridine (BrdU) and the polysialylated form of neural cell adhesion molecule (PSA‐NCAM) immunostaining, as observed in 2‐month‐survival rats. The raphe grafts, but not the control grafts of embryonic spinal tissue, reversed the postlesion‐induced decreases in the density of BrdU‐ and PSA‐NCAM‐labelled cells detected in the granule layer. Inhibition of serotonin synthesis in animals with raphe grafts reversed back to lesion‐induced changes in granule cell proliferation. Furthermore, extensive serotonergic reinnervation of the dentate gyrus in the area proximal to the raphe graft could be associated with supranormal density of BrdU‐labelled cells. These results indicate that serotonin may be considered a positive regulatory factor of adult granule cell proliferation. Finally, the lack of effect of embryonic nonserotonergic tissue grafted to serotonin‐deprived rats suggests that neurotrophic factors may not be involved in the effects of serotonin on adult neurogenesis.
Anisomycin uses multiple mechanisms to stimulate mitogen‐activated protein kinases and gene expression and to inhibit neuronal differentiation in PC12 phaeochromocytoma cells
Authors: Töro"csik Beáta , Szeberényi József 
Published: March 2003

AbstractTreatment of PC12 cells with nerve growth factor (NGF) stimulates extracellular signal‐regulated kinases (ERKs), as well as stress‐activated c‐Jun N‐terminal kinases (JNKs) and p38 kinase, and induces neuronal differentiation. While the pivotal role of ERKs in NGF‐induced morphological differentiation is well established, the contribution of JNK‐ and p38‐pathways is less clear. The role of the JNK‐ and p38‐pathway in PC12 cells was analysed by using anisomycin, a protein synthesis inhibitor that activates JNKs and p38. Non‐toxic concentrations of anisomycin were found to stimulate these enzyme activities as well as the expression of the early response genes c‐jun, c‐fos and zif268, and to inhibit NGF‐induced neurite formation. These effects of anisomycin appear to be mediated by the generation of reactive oxygen species (ROS), which in turn act through both TrkA/Ras‐dependent and ‐independent signalling pathways. In addition, cross‐talk between the p38‐ and ERK‐pathways appears to play a role in the action of anisomycin.
Is right hemisphere specialization for face discrimination specific to humans?
Authors: Broad Kevin D. , Mimmack Michael L. , Kendrick Keith M. 
Published: March 2003

AbstractPatterns of neural activation during face recognition were investigated in sheep by quantifying altered c‐fos mRNA expression in situations where faces (sheep vs. human) can (faces upright) and cannot (faces inverted) be discriminated. Exposure to upright faces selectively increased expression significantly more in the right inferior temporal cortex than in the left, and active choice between upright faces additionally increased expression bilaterally in basal amygdala and hippocampus (CA1–4). Exposure to inverted faces did not lead to enhanced activation in the right inferior temporal cortex, amygdala or hippocampus but instead increased expression levels in the diagonal band of Broca, parietal and cingulate cortices. These results show that discrimination of upright faces in sheep preferentially engages the right temporal cortex, as it does in humans, and that performance of active choices between such faces may additionally involve the basal amygdala and hippocampus.
Responses to linear and logarithmic frequency‐modulated sweeps in ferret primary auditory cortex
Authors: Nelken Israel , Versnel Huib 
Published: March 2003

AbstractMulti‐unit responses to frequency‐modulated (FM) sweeps were studied in the primary auditory cortex of ferrets using six different stimulation paradigms. In particular, the differences between the responses to linear FM sweeps (where frequency changes linearly with time) and logarithmic FM sweeps (where frequency changes exponentially with time) were emphasized. Some general features of the responses to FM sweeps are independent of the exact details of the frequency trajectory. Both for linear and for logarithmic FM sweeps, a short burst of spikes occurred when the sweep reached a triggering frequency close to the best frequency of the cluster. The neuronal preference for FM velocity was also independent of frequency trajectory. Thus, clusters that responded best to slow logarithmic FM also preferred slow linear FM and vice versa. Consequently, topographic distributions of velocity preference were roughly independent of the stimulation paradigm. Other characteristics of the responses, however, depended on the exact details of the frequency trajectory. A significant number of clusters showed large differences in directional sensitivity between linear and logarithmic FM sweeps; these differences depended on the velocity preference of the clusters in some paradigms but not in others. Consequently, topographic distributions of directional sensitivity differed between linear and logarithmic paradigms. In conclusion, some characteristics of cluster responses to FM sweeps depend on the exact details of the stimulation paradigm and are not ‘invariants’ of the cluster.
Specific activation of the μ opioid receptor (MOR) by endomorphin 1 and endomorphin 2
Authors: Monory Krisztina , Bourin Marie‐Claude , Spetea Mariana , Tömböly Csaba , Tóth Géza , Matthes Hans W. , Kieffer Brigitte L. , Hanoune Jacques , Borsodi Anna 
Published: March 2003

AbstractThe recently discovered endomorphin 1 (Tyr‐Pro‐Trp‐Phe‐NH2) and endomorphin 2 (Tyr‐Pro‐Phe‐Phe‐NH2) were investigated with respect to their direct receptor‐binding properties, and to their ability to activate G proteins and to inhibit adenylyl cyclase in both cellular and animal models. Both tetrapeptides activated G proteins and inhibited adenylyl cyclase activity in membrane preparations from cells stably expressing the μ opioid receptor, an effect reversed by the μ receptor antagonist CTAP (d‐Phe‐Cys‐Tyr‐d‐Trp‐Arg‐Thr‐Pen‐Thr‐NH2), but they had no influence on cells stably expressing the δ opioid receptor. To further establish the selectivity of these peptides for the μ opioid receptor, brain preparations of mice lacking the μ opioid receptor gene were used to study their binding and signalling properties. Endomorphin 2, tritiated by a dehalotritiation method resulting in a specific radioactivity of 1.98 TBq/mmol (53.4 Ci/mmol), labelled the brain membranes of wild‐type mice with a Kd value of 1.77 nm and a Bmax of 63.33 fmol/mg protein. In membranes of mice lacking the μreceptor gene, no binding was observed, and both endomorphins failed to stimulate [35S]guanosine‐5′‐O‐(3‐thio)triphosphate ([35S]GTPγS) binding and to inhibit adenylyl cyclase. These data show that endomorphins are capable of activating G proteins and inhibiting adenylyl cyclase activity, and all these effects are mediated by the μ opioid receptors.
Hippocampal participation in navigational map learning in young homing pigeons is dependent on training experience
Authors: Ioalè Paolo , Gagliardo Anna , Bingman Verner P. 
Published: March 2003

AbstractThe homing pigeon navigational map is perhaps one of the most striking examples of a naturally occurring spatial representation of the environment used to guide navigation. In a previous study, it was found that hippocampal lesions thoroughly disrupt the ability of young homing pigeons held in an outdoor aviary to learn a navigational map. However, since that study an accumulation of anecdotal data has hinted that hippocampal‐lesioned young pigeons allowed to fly during their first summer could learn a navigational map. In the present study, young control and hippocampal‐lesioned homing pigeons were either held in an outdoor aviary or allowed to fly during the time of navigational map learning. At the end of their first summer, the birds were experimentally released to test for navigational map learning. Independent of training experience, control pigeons oriented homeward during the experimental releases demonstrating that they learned a navigational map. Surprisingly, while the aviary‐held hippocampal‐lesioned pigeons failed to learn a navigational map as reported previously, hippocampal‐lesioned birds allowed flight experience learned a navigational map indistinguishable from the two control groups. A subsequent experiment revealed that the navigational map learned by the three groups was based on atmospheric odours. The results demonstrate that hippocampal participation in navigational map learning depends on the type of experience a young bird pigeon has, and presumably, the type of navigational map learned.
Clustering of δ glutamate receptors is regulated by the actin cytoskeleton in the dendritic spines of cultured rat Purkinje cells
Authors: Hirai Hirokazu 
Published: March 2003

AbstractThe interaction of neurotransmitter receptors with the cytoskeleton is an important mechanism for the targeting of receptors to the postsynaptic membrane. Using cytoskeleton‐perturbing agents, it was demonstrated that δ glutamate receptors, predominantly expressed on the dendritic spines of cerebellar Purkinje cells, are anchored to the actin cytoskeleton. The number of δ glutamate receptor‐immunoreactive clusters was dramatically decreased following treatment of the Purkinje cells with the actin‐disrupting agents, cytochalasin D or latrunculin A, without any significant effect on the number of presynaptic contacts of the granule cell axons. The clusters disrupted by latrunculin A were re‐established 24 h after removal of the drug. These results suggest that morphological changes in the actin cytoskeleton regulate the δ glutamate receptor clustering on the dendritic spines, and may affect synaptic efficacy and plasticity.
Circadian modulation of calcium levels in cells in the suprachiasmatic nucleus
Authors: Colwell Christopher S. 
Published: March 2003

AbstractThere is reason to believe that resting free calcium concentration [Ca2+]i in neurons in the suprachiasmatic nucleus (SCN) may vary with the circadian cycle. In order to start to examine this hypothesis, optical techniques were utilized to estimate resting Ca2+ levels in SCN cells in a rat brain slice preparation. [Ca2+]i measured from the soma was significantly higher in the day than in the night. Animals from a reversed light–dark cycle were used to confirm that the phase of the rhythm was determined by the prior light–dark cycle. The rhythm in Ca2+ levels continued to be expressed in tissue collected from animals maintained in constant darkness, thus confirming the endogenous nature of this variation. Interestingly, the rhythm in Ca2+ levels was not observed when animals were housed in constant light. Finally, the rhythm in Ca2+ levels was prevented when slices were exposed to tetrodotoxin (TTX), a blocker of voltage‐sensitive sodium channels. Similar results were obtained with the voltage‐sensitive Ca2+ channel blocker methoxyverapamil. These observations suggest a critical role for membrane events in driving the observed rhythm in Ca2+. Conceptually, this rhythm can be thought of as an output of the circadian oscillator. Because [Ca2+]i is known to play a critical role in many cellular processes, the presence of this rhythm is likely to have many implications for the cell biology of SCN neurons.
Overexpression of spermidine/spermine N1‐acetyltransferase in transgenic mice protects the animals from kainate‐induced toxicity
Authors: Kaasinen Kyllikki , Koistinaho Jari , Alhonen Leena , Jänne Juhani 
Published: March 2003

AbstractWe recently generated a transgenic mouse line with activated polyamine catabolism through overexpression of spermidine/spermine N1‐acetyltransferase (SSAT). A detailed analysis of brain polyamine concentrations indicated that all brain regions of these animals showed distinct signs of activated polyamine catabolism, e.g. overaccumulation of putrescine (three‐ to 17‐fold), appearance of N1‐acetylspermidine and decreases in spermidine concentrations. In situ hybridization analyses revealed a marked overexpression of SSAT‐specific mRNA all over the brain tissue of the transgenic animals. The transgenic animals appeared to tolerate subcutaneous injections of high‐dose kainate substantially better as their overall mortality was less than 50% of that of their syngenic littermates. We used the expression of glial fibrillary acidic protein (GFAP) as a marker of brain injury in response to kainate. In situ hybridization analysis with GFAP oligonucleotide up to 7 days after the administration of sublethal kainate doses showed reduced GFAP expression in transgenic animals in comparison with their non‐transgenic littermates. This difference was especially striking in the cerebral cortex of the transgenic mice where the exposure to kainate hardly induced GFAP expression. The treatment with kainate likewise resulted in loss of the hippocampal (CA3) neurons in non‐transgenic but not transgenic animals. These results support our earlier findings indicating that elevated concentrations of brain putrescine, irrespective whether derived from an overexpression of ornithine decarboxylase, or as shown here, from an overexpression of SSAT, play in all likelihood a neuroprotective role in brain injury.