bluuebunny/crossref_metadata_2025_split huggingface dataset:
FGF‐2 Modulates Dopamine and Dopamine‐related Striatal Transmitter Systems in the Intact and MPTP‐lesioned Mouse
Authors: Otto Dörte , Unsicker Klaus 
Published: April 2006

AbstractFollowing a previous study in which we showed ameliorative effects of basic fibroblast growth factor (FGF‐2) locally applied to the nigrostriatal system in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐lesioned mice, we investigated FGF‐2 actions at different time intervals after the lesion and effects on non‐dopaminergic striatal transmitter systems. A triple intraperitoneal injection of 30 mg/kg MPTP at 24 h intervals caused a reduction of striatal dopamine to 23% of control levels that lasted for at least 4 weeks. Four μg FGF‐2 soaked into gel foam and placed onto the right striatum partially and bilaterally restored dopamine levels and tyrosine hydroxylase activity after 2 weeks, when the treatment started simultaneously or 1 day after the toxin lesion. FGF‐2 was ineffective, if administration commenced with a delay of 7 days. Striatal neurotransmitters that are known to be linked to the dopaminergic system were also altered by the MPTP treatment. GABA was significantly increased, while somatostatin levels were reduced. Upon FGF‐2 administration both GABA and somatostatin levels were partially normalized. Our data are consistent with the notion that FGF‐2 protects and rescues acutely and subacutely MPTP‐lesioned nigrostriatal neurons and that its effects must be mainly indirect. Likewise, positive effects of FGF‐2 on non‐dopaminergic neurons may be due to the partial restoration of striatal dopamine.
Neuroprotective Effect of the χ‐Agonist Enadoline (CI‐977) in Rat Models of Focal Cerebral Ischaemia
Authors: Hayward Neil James , McKnight Alexander Thorburn , Woodruff Geoffrey Neil 
Published: April 2006

AbstractThe neuroprotective efficacy of the χ‐opioid agonist enadoline (CI‐977) was examined in two acute rat models of focal cerebral ischaemia [non‐recovery (4 h) and recovery (24 h)]. In the non‐recovery model, Sprague ‐ Dawley rats were anaesthetized throughout the study period. Focal ischaemia was produced by the permanent occlusion of the left middle cerebral artery (MCA). The amount of early ischaemic damage was assessed in coronal sections at nine pre‐determined stereotaxic planes. Enadoline at doses of 0.1, 0.3 and 1.0 mg/kg (n= 8), administered s.c. 30 min prior to ischaemia, produced dose‐dependent amelioration of cortical damage. Importantly, enadoline had no significant effect on any of the physiological parameters monitored (blood pressure, blood gases, glucose, pH). In the recovery model the left MCA was permanently occluded under isoflurane anaesthesia. Animals were allowed to recover and were killed 24 h later. The amount of ischaemic brain damage and swelling was assessed histologically. In this model pretreatment with enadoline at either 0.1, 0.3, or 1.0 mg/kg s.c. was followed by continuous s.c. infusion at 0.017, 0.05 or 0.17 mg/kg/h respectively (n= 8–17). Enadoline produced dose‐dependent reductions in the volumes of infarction and brain swelling; the greatest reductions were seen at 1.0 mg/kg plus 0.17 mg/kg/h in both infarction (reduced by 37.4% from controls) and swelling (reduced by 47.8%). Therefore the χ‐opioid agonist enadoline affords dose‐dependent neuroprotection in both the non‐recovery and recovery models of focal cerebral ischaemia in the rat. In the recovery model enadoline was effective in reducing infarction and oedema; the reduction in brain swelling occurs in parallel with the reduction in ischaemic damage.
Trophic Actions of Ciliary Neurotrophic Factor on Murine Embryonic Carcinoma Cells
Authors: Gupta S. K. , Haggarty A. J. , Carbonetto S. , Riopelle R. J. , Richardson P. M. , Dunn R. J. 
Published: April 2006

AbstractRecombinant rat CNTF (ciliary neurotrophic factor) at picomolar concentration prevents the death of P19 murine embryonic carcinoma cells that usually follows upon withdrawal of serum from the culture medium. For prolonged survival of P19 cells in serum‐free medium, insulin must also be present. In the presence or absence of serum, CNTF stimulates the differentiation of P19 cells, inducing the formation of neurites and synthesis of neurofilament. The results of radioautographic studies with radioiodinated CNTF indicate the presence of high‐affinity binding sites on P19 cells. Equilibration of P19 cells with [125I]CNTF followed by incubation with cross‐linking reagents reveals evidence for at least two putative receptors of ∼78 and ∼167 kDa.
Voltage‐dependent Currents in Microvillar Receptor Cells of the Frog Vomeronasal Organ
Authors: Trotier Didier , Døving Kjell B. , Rosin Jean‐François 
Published: April 2006

AbstractVomeronasal receptor cells are differentiated bipolar neurons with a long dendrite bearing numerous microvilli. Isolated cells (with a mean dendritic length of 65 μm) and cells in mucosal slices were studied using whole‐cell and Nystatin‐perforated patch‐clamp recordings. At rest, the membrane potential was −61 ± 13 mV (mean ± SD; n= 61). Sixty‐four per cent of the cells had a resting potential in the range of –60 to –86 mV, with almost no spontaneous action potential. The input resistance was in the GΩ range and overshooting repetitive action potentials were elicited by injecting depolarizing current pulses in the range of 2 – 10 pA. Voltage‐dependent currents were characterized under voltage‐clamp conditions. A transient fast inward current activating near –45 mV was blocked by tetrodotoxin. In isolated cells, it was half‐deactivated at a membrane potential near –75 mV. An outward K+ current was blocked by internal Cs+ ions or by external tetraethylammonium or Ba2+ ions. A calcium‐activated voltage‐dependent potassium current was blocked by external Cd2+ ions. A voltage‐dependent Ca2+ current was observed in an iso‐osmotic BaCl2 solution. Finally, a hyperpolarization‐activated inward current was recorded. Voltage‐dependent currents in these microvillar olfactory receptor neurons appear qualitatively similar to those already described in ciliated olfactory receptor cells located in the principal olfactory epithelium.
Processing of the FMRFamide Precursor Protein in the Snail Lymnaea stagnalis: Characterization and Neuronal Localization of a Novel Peptide, ‘SEEPLY’
Authors: Santama Niovi , Wan Li Ka , Bright Kerris E. , Yeoman Mark , Geraerts Wijnand P. M. , Benjamin Paul R. , Burke Julian F. 
Published: April 2006

AbstractIn the pulmonate snail Lymnaea stagnalis, FMRFamide‐like neuropeptides are encoded by a multi‐exon genomic locus which is subject to regulation at the level of mRNA splicing. We aim to understand the post‐translational processing of one resulting protein precursor encoding the tetrapeptide FMRFamide and a number of other putative peptides, and determine the distribution of the final peptide products in the central nervous system (CNS) and periphery of Lymnaea. We focused on two previously unknown peptide sequences predicted by molecular cloning to be encoded in the tetrapeptide protein precursor consecutively, separated by the tetrabasic cleavage site RKRR. Here we report the isolation and structural characterization of a novel non‐FMRFamide‐like peptide, the 22 amino acid peptide SEQPDVDDYLRDWLQSEEPLY. The novel peptide is colocalized with FMRFamide in the CNS in a number of identified neuronal systems and their peripheral motor targets, as determined by in situ hybridization and immunocytochemistry. Its detection in heart excitatory motoneurons and in nerve fibres of the heart indicated that the novel peptide may play a role, together with FMRFamide, in heart regulation in the snail. The second predicted peptide, STEAGGQSEEMTHRTA (16 amino acids), was at very low abundance in the CNS and was only occasionally detected. Our current findings, suggestive of a distinct pattern of post‐translational processing, allowed the reassessment of a previously proposed hypothesis that the two equivalent sequences in the Aplysia FMRFamide gene constitute a molluscan homologue of vertebrate corticotrophin releasing factor‐like peptides.
Detection of a Purine Analogue‐sensitive Kinase in Frog Sciatic Nerves—Possible Involvement in Nerve Regeneration
Authors: Svensson Bodil , Biessels Geert‐Jan , Per Ekström  
Published: April 2006

AbstractThis study reports the existence of a purine analogue‐sensitive protein kinase in adult frog sciatic nerves. Cell‐free supernatants of homogenized regenerating sclatic nerves were found to contain a phosphoprotein (MW 90 kDa, referred to as PP90), that was phosphorylated to a much higher degree than in normal, uninjured nerves. The spatial and temporal characteristics of PP90 phosphorylation suggested a relationship with the injury‐induced proliferation of support cells of the regenerating nerve, i.e. its appearance and increment over time correlated with that of [3H]thymidine incorporation in the nerve. PP90 was phosphorylated under conditions that excluded enzyme activities due to Ca2+/calmodulin kinases, cyclic nucleotide‐dependent kinases or protein kinase C. On the other hand, the phosphorylation could be selectively inhibited by the purine analogues adenosine, 2‐aminopurine and 6‐thioguanine (6‐TG). The latter was the most potent and gave complete inhibition at 50 μM. Addition of histone H1 to the cell‐free assay stimulated the phosphorylation of several proteins in both normal and regenerating nerves. The stimulation could be blocked by 6‐TG, indicating the presence of a purine‐sensitive kinase also in uninjured nerves. Separate experiments showed that in vitro regeneration of the frog sciatic sensory axons, as well as the proliferation of the support cells, was inhibited by 100 μM 6‐TG.
Functional Heterogeneity of Hippocampal GABAA Receptors
Authors: Schönrock Beate , Bormann Joachim 
Published: April 2006

Abstractγ‐Aminobutyric acid type A (GABAA) receptors were studied in cultured neurons taken from rat hippocampus at early postnatal stages. GABA‐induced whole‐cell currents showed a broad range of peak amplitudes and time‐courses of desensitization. Dose – response curves of rapidly and slowly desensitizing cells revealed EC50 values of 8.5 and 37.3 μM GABA, respectively, with the Hill coefficient being greater than unity. The main‐state conductance of GABAA receptor channels was 28 – 31 pS in all cells. GABA responses of low‐affinity cells were more strongly affected by benzodiazepine receptor agonists (e.g. flunitrazepam, clonazepam) and inverse agonists (e.g. methyl‐6,7‐dimethoxy‐4‐ethyl‐β‐carboline‐3‐carboxylate), as compared to cells exhibiting high‐affinity GABA responses. Currents were also potentiated by zolpidem, but were little affected by Ro 15‐4513 and Zn2+. These data suggest the presence of physiologically and pharmacologically distinct GABAA receptor isoforms in neurons of the early postnatal hippocampus, which may subserve different inhibitory control mechanisms in this brain region.
Enrichment of Glutamate‐like Immunoreactivity in Primary Afferent Terminals Throughout the Spinal Cord Dorsal Horn
Authors: Broman Jonas , Anderson Sonya , Ottersen Ole P. 
Published: April 2006

AbstractAlthough several lines of evidence indicate that glutamate is a neurotransmitter in primary afferent terminals, controversies exist on the proportion and types of such terminals that release glutamate. In the present study quantitative analysis of immunogold labelling was used to assess the presence of glutamate‐like immunoreactivity in primary afferent terminals in laminae I – V of the rat spinal cord dorsal horn. Anterograde transport of choleragenoid – horseradish peroxidase from a spinal ganglion and tetramethyl benzidine histochemistry were used to identify primary afferent terminals in laminae I and III – V. Presumed C‐fibre terminals in lamina II were identified on morphological criteria (dense sinusoid axon terminals). Primary afferent terminals in all dorsal horn laminae displayed significantly higher levels of glutamate‐like immunoreactivity than pleomorphic vesicle‐containing profiles in laminae III – IV and large neuronal cell bodies in laminae III – V. The density of gold particles over primary afferent terminals also significantly exceeded the average density of gold particles over laminae II and III – IV. The highest densities of gold particles were present over dense sinusoid axon terminals in lamina II. These findings suggest that glutamate, alone or in combination with other neuroactive compounds, is involved in the transfer of all sensory modalities from primary afferent fibres to dorsal horn neurons.
Muscle Afferents Innervating Skin Form Somatotopically Appropriate Connections in the Adult Rat Dorsal Horn
Authors: Lewin Gary R. , McMahon Stephen B. 
Published: April 2006

AbstractWe have studied the somatotopic reorganization in dorsal horn neurons after a disruption in the normal spatial arrangement of primary sensory axons in adult rats. Muscle afferents were redirected to skin by cutting and cross‐anastomosing the hindlimb gastrocnemius nerve (GN) and sural nerve (SN). It has previously been shown that after 10 – 12 weeks GN afferents innervate the hairy skin of the lateral ankle and calf (previously innervated by SN afferents) and become potentially capable of relaying information on the location and intensity of stimuli applied to the skin. We determined the receptive field and response properties of dorsal horn neurons in the lumbar spinal cord, in regions where the lower hindlimb is normally represented. In control animals (with intact or self‐anastomosed sural nerves) very few neurons (<8%) received any synaptic input from the GN as assessed by electrical stimulation of the nerve. In contrast, when this nerve innervated skin, many cells responded to GN stimulation, and these nearly all had receptive field components in the former SN territory. Moreover, in animals with cross‐anastomosed nerves, cells without GN inputs all had receptive fields outside the former SN skin territory. We have shown that in all likelihood GN afferents substituted for SN afferents in subserving the low and high threshold receptive fields of dorsal horn neurons. Furthermore, for many neurons, receptive fields were formed from inappropriately regrown GN afferents and adjacent intact cutaneous afferents (in the tibial or common peroneal nerves). Therefore, when GN afferents innervate skin in adult animals, they alter their central connectivity in an appropriate manner for their new peripheral terminations, so that an orderly somatotopic representation of the hind limb skin is maintained. We suggest that this plasticity of dorsal horn somatotopy is driven in part by activity‐dependent mechanisms.
Functional Topography of the Myelin‐associated Glycoprotein. I. Mapping of Domains by Electron Microscopy
Authors: Fahrig Thomas , Probstmeier Rainer , Spiess Eberhard , Meyer‐Franke Anke , Kirchhoff Frank , Drescher Bernd , Schachner Melitta 
Published: April 2006

AbstractThe functional topography of the myelin‐associated glycoprotein (MAG) was investigated by electron microscopic analysis of rotary‐shadowed molecules of a MAG fragment (MAG 90) comprising the five immunoglobulin‐like domains of the extracellular part of the molecule. MAG 90 molecules appeared as rod‐like structures (18.5±1.2 nm long and 4.0±0.8 nm wide) with a globular domain at one end. Antibodies directed against the amino‐ and carboxy‐terminus of MAG 90 interacted with the non‐globular terminal region, indicating that the molecule is bent in the globular region with the amino‐ and carboxy‐terminal arms in close apposition to each other. An antibody which interferes with the binding of MAG to neurons interacted predominantly with the globular domain of MAG 90. The fibril‐forming collagen types I, III and V bound mainly to the non‐globular terminal region of MAG 90, whereas the majority of heparin molecules interacted with the globular region of the molecule. The L2/HNK‐1 carbohydrate structure was localized at the non‐globular region in the protein fragment comprising the fourth and fifth immunoglobulin‐like domains.
Persistence of Axonal Transport in Isolated Axons of the Mouse
Authors: Smith R. S. , Bisby M. A. 
Published: April 2006

AbstractWe have examined the hypothesis, for the case of mouse axons, that isolating an axon from its cell body will lead to a rapid failure of fast axonal transport as anterogradely moving organelles vacate the axon in a proximo‐distal direction, and retrogradely moving organelles vacate it in the opposite direction. We used CD1 and BALB/c mice and the Wallerian degeneration‐resistant mutant C57BL/Ola. Sciatic nerves were cut high in the thigh; at various times up to 8 days later nerves were removed from the animal and individual myelinated axons from the segment distal to the cut were examined by video light microscopy to detect rapid organelle transport. Bidirectional fast organelle transport did decrease in amount with time but not nearly as rapidly as predicted, and anterograde and retrograde organelle velocities remained normal through time. In the C57BL/Ola mouse some structurally preserved axons contained organelles that transported at normal velocities in the anterograde and retrograde directions for as long as 8 days after axotomy. To test one of the possible origins of transported organelles in long‐surviving axons we examined organelle transport very close to narrow lesions in axons bathed in a medium compatible with intracellular function. No organelles crossed the lesion but bidirectional organelle transport took place proximal and distal to the lesion; the amounts were compatible with the interpretation that ∼30% of organelles reversed transport direction on either side of the lesion. We propose that at least some of the organelles that undergo persistent transport in axons isolated from their cell bodies shuttle back and forth between the ends of the isolated segment.
Tracing Neuroepithelial Cells of the Mesencephalic and Metencephalic Alar Plates During Cerebellar Ontogeny in Quail – chick Chimaeras
Authors: Hallonet Marc E. R. , Le Douarin Nicole M. 
Published: April 2006

AbstractThe quail – chick chimaera system was used to investigate the origin of the various neuronal cell types of the cerebellum from the mesencephalic and metencephalic brain vesicles at the 11‐ to 14‐somite stage in the avian embryo. We have already demonstrated that the cerebellum is derived from both the mesencephalic and metencephalic brain vesicles. The mesencephalic contribution to the cerebellum is restricted to a mediodorsal territory inserted as a V‐shaped area into the primitive metencephalic vesicle through complex morphogenetic movements taking place from day 2 to day 4 of embryonic development. Here we report that the cerebellar presumptive territory extends along the anteroposterior axis, over the caudal half of the mesencephalon and the rostral half of the metencephalon. Along the dorsoventral axis, the cerebellar anlage is located in the alar plates at the exclusion of the roof and basal plates, i.e. lies in the lateral walls of the neuroepithelium in the area included between ∼25 and 120° with respect to the sagittal plane. We also report that the neuroepithelium corresponding to the cerebellar presumptive territory also yields other brain structures (e.g. part of the optic tectum in the mesencephalon). The external granular layer (EGL) arises only from the rostral metencephalon, undergoing extensive tangential movements which we have analysed in detail: the more ventral the position of cells in the metencephalic alar plates the more rostral and lateral is their position in the EGL. Finally, we discuss the fact that the cerebellar cortex, an integrative structure of the brain, arises from the alar plates of the neural tube. This is consistent with the general spatial organization of the neural anlage of the vertebrate embryo, in which this part of the neuroepithelium is devoted to the production of interneurons, whereas the basal plate and the neural folds yield motor structures and primary sensory neurons respectively.
In Vitro Enfolding of Olfactory Neurites by p75 NGF Receptor Positive Ensheathing Cells from Adult Rat Olfactory Bulb
Authors: Ramón‐Cueto Almudena , Pérez Julio , Nieto‐Sampedro Manuel 
Published: April 2006

AbstractSecondary cultures of adult rat olfactory bulb (OB) contained three different types of cell: (i) process‐bearing cells; (ii) macrophage‐like cells and (iii) fusiform cells. The immunohistochemical properties of process‐bearing cells closely corresponded to those described for ensheathing glia in vivo. The most distinctive feature of these cells was their immunoreactivity for low affinity nerve growth factor receptor (NGFR). Process‐bearing cells also shared the ultrastructural properties of ensheathing glia in vivo, as well as the ability to ensheath olfactory axons. In contrast, macrophage‐like cells had the immunostaining properties of microglia, and fusiform cells were likely capillary endothelial cells.Neurites outgrowing from olfactory epithelium explants, when co‐cultured with adult OB cells, grew preferentially over NGFR positive cells. Olfactory neurites exhibited NGFR immunoreactivity and were enfolded by NGFR positive cells. After ensheathment, this immunoreactivity decreased from the neurite and disappeared from the glial membrane in contact with the neurite. However, NGFR immunoreactivity was maintained in the portion of the glial membrane not involved in ensheathing. In summary, ensheathing cells in vitro retained both the ultrastructure shown in vivo and the ability to ensheath olfactory neurites. The Schwann cell‐like properties of ensheathing glia, could partially explain the permissibility of adult OB to axonal growth.
Carbachol Potentiates Q Current and Activates a Calcium‐dependent Non‐specific Conductance in Rat Hippocampus In Vitro
Authors: Colino A. , Halliwell J. V. 
Published: April 2006

AbstractIntracellular recordings were made from CA1 neurons in rat hippocampal slices maintained in vitro. When Na+ currents were blocked with tetrodotoxin and K+ conductances known to be sensitive to suppression by muscarinic agonists were blocked by 2 mM Ba2+, CA1 cells were depolarized by carbachol (3 – 10 μM) with an attendant conductance increase, whereas prior to Ba2+ the agonist produced a decrease or no change in conductance. Under voltage clamp at ∼–60 mV and in the presence of tetrodotoxin and Ba2+, carbachol (3 – 10 μM) induced a variable‐latency biphasic inward current of up to 380 pA associated with a conductance increase of ∼50%. The first phase was associated with an increase (more than 2‐fold) of the Cs+‐sensitive, hyperpolarization‐activated cationic current, IQ. Carbachol also accelerated the kinetics of IQ at – 100 mV with an average 24% reduction in its activation time constant. The second phase reflected an additional inward current that was Cs+‐resistant, displayed little apparent voltage sensitivity and had a mean extrapolated reversal potential, determined in the presence of external Cs+ (>5 mM), of ∼–20 mV. In a small proportion of cells the second phase of inward current was followed (or overlapped) by an outward current, also associated with a conductance increase, which reversed at ∼–70 mV. These carbachol actions were prevented by extracellular 300 μM Cd2+ and 2 mM Mn2+, by high levels (>5 mM) of extracellular Mg2+ or Ca2+, and by omission of Ca2+ or reduction of extracellular Na+ to 25 mM by substitution of NaCl with Tris or N‐methyl‐d‐glucamine. Carbachol action was not mimicked by oxotremorine (≤60 μM), but was irreversibly blocked by this drug. Likewise, atropine (100 nM) irreversibly and gallamine (10 μM) reversibly antagonized carbachol's action. The action of carbachol was blocked shortly after prior exposure of slices to 2 – 5 mM caffeine. Chronic or acute incubation of slices with 2 mM Li+ potentiated (between 1‐ and 2‐fold) carbachol responses. The data indicate that muscarinic activation increases cationic flux by a calcium‐dependent potentiation of IQ and activation of a non‐selective conductance. The probability that inositol phospholipid metabolism is involved in triggering these events is discussed.