bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adrenergic innervation of rat sensory ganglia following proximal or distal painful sciatic neuropathy: distinct mechanisms revealed by anti‐NGF treatment
Authors: Ramer Matt S. , Bisby Mark A. 
Published: March 2003

AbstractSympathetic axons invade dorsal root ganglia (DRG) following nerve injury, and activity in the resulting pericellular axonal ‘baskets’ may underlie painful sympathetic–sensory coupling. Sympathetic sprouting into the DRG may be stimulated by nerve growth factor (NGF). To test this hypothesis, we investigated the effect of daily anti‐NGF administration on pain and on sprouting in the DRG induced by chronic sciatic constriction injury (CCI) or L5 spinal nerve ligation (SNL). These models have been shown to differ subtly in the onset of pain behaviours and adrenergic sprouting, and we now demonstrate a fundamental difference in the way sympathetic axons invade the DRG: after CCI, perivascular noradrenergic collaterals sprouted into the DRG in a manner dependent upon peripherally derived NGF. In contrast, after SNL, regenerating sympathetic axons were diverted towards the DRG from the spinal nerve by the obstructing ligature, and this effect was only moderately impeded by anti‐NGF. The differential dependence on anti‐NGF suggests that adrenergic innervation of the DRG after SNL and CCI may reflect regenerative and collateral sprouting, respectively. Pain behaviour was similarly affected: anti‐NGF completely prevented CCI‐induced thermal hyperalgesia and mechanoallodynia, but the same treatment only partly relieved these symptoms following SNL. These differences emphasize that although CCI and SNL may result in similar behavioural abnormalities, the underlying mechanisms may be governed by distinct processes, differentially dependent on peripheral NGF. These mechanistic differences will have to be considered in the development of appropriate treatment strategies for neuropathic pain produced by different types of pathology.
Callosal connections of the parabelt auditory cortex in macaque monkeys
Authors: Hackett T. A. , Stepniewska I. , Kaas J. H. 
Published: March 2003

AbstractAuditory cortex of macaque monkeys is located on the lower bank of the lateral sulcus and the adjoining superior temporal gyrus. This region of cortex contains a core of primary‐like areas surrounded by a narrow belt of associated fields. Adjacent to the lateral belt on the superior temporal gyrus is a parabelt region which contains at least two subdivisions (rostral and caudal). In previous studies we defined the parabelt region as cortex with topographic cortical connections with the belt areas surrounding the core, and connections with the dorsal and magnocellular divisions of the medial geniculate complex, but minimal connections with the core region and ventral division of the medial geniculate complex. The callosal connections of the parabelt auditory cortex were determined by placing injections, of up to six distinguishable tracers, into different locations of the parabelt region in each of four macaque monkeys. The results indicated that the strongest callosal projections arise from homotopic areas in parabelt cortex, and they roughly matched the rostrocaudal levels of the medial and lateral belt cortex. Weaker callosal inputs to the parabelt originate from the corresponding levels of the superior temporal gyrus and superior temporal sulcus. The core region does not contribute significant callosal projections to the parabelt region. The results provide further support for the conclusion that the parabelt region represents a third level of auditory cortical processing beyond direct activation by primary subcortical and cortical auditory structures.
Functional role of the slow activation property of ERG K+ channels
Authors: Schönherr Roland , Rosati Barbara , Hehl Solveig , Rao Valesvara G. , Arcangeli Annarosa , Olivotto Massimo , Heinemann Stefan H. , Wanke Enzo 
Published: March 2003

AbstractERG (ether‐à‐go‐go‐related gene) K+ channels are crucial in human heart physiology (h‐ERG), but are also found in neuronal cells and are impaired in Drosophila‘seizure’ mutants. Their biophysical properties include the relatively fast kinetics of the inactivation gate and much slower kinetics of the activation gate. In order to elucidate how the complex time‐ and voltage‐dependent activation properties of ERG channels underlies distinct roles in excitability, we investigated different types of ERG channels intrinsically present in cells or heterologously expressed in mammalian cells or Xenopus oocytes. Voltage‐dependent activation curves were highly dependent on the features of the eliciting protocols. Only very long preconditioning times produced true steady‐state relationships, a fact that has been largely neglected in the past, hampering the comparison of published data on ERG channels. Beyond this technical aspect, the slow activation property of ERG can be responsible for unsuspected physiological roles. We found that around the midpoint of the activation curve, the time constant of ERG open–close kinetics is of the order of 10–15 s. During sustained trains of depolarizations, e.g. those produced in neuronal firing, this leads to the use‐dependent accumulation of open‐state ERG channels. Accumulation is not observed in a mutant with a fast activation gate. In conclusion, it is well established that other K+ channels (i.e. Ca2+‐activated and M) control the spike‐frequency adaptation, but our results support the notion that the purely voltage‐dependent activation property of ERG channels would allow a slow inhibitory physiological role in rapid neuronal signalling.
CNS pattern of metabolic activity during tonic pain: evidence for modulation by β‐endorphin
Authors: Porro Carlo A. , Cavazzuti Milena , Baraldi Patrizia , Giuliani Daniela , Panerai Alberto E. , Corazza Ruggero 
Published: March 2003

AbstractCNS correlates of acute prolonged pain, and the effects of partial blockade of the central β‐endorphin system, were investigated by the quantitative 2‐deoxyglucose technique in unanaesthetized, freely moving rats. Experiments were performed during the second, tonic phase of the behavioural response to a prolonged chemical noxious stimulus (s.c. injection of dilute formalin into a forepaw), or after minor tissue injury (s.c. saline injection). During formalin‐induced pain, local glucose utilization rates in the CNS were bilaterally increased in the grey matter of the cervical spinal cord, in spinal white matter tracts and in several supraspinal structures, including portions of the medullary reticular formation, locus coeruleus, lateral parabrachial region, anterior pretectal nucleus, the medial, lateral and posterior thalamic regions, basal ganglia, and the parietal, cingulate, frontal, insular and orbital cortical areas. Pretreatment with anti‐β‐endorphin antibodies, injected i.c.v., led to increased metabolism in the tegmental nuclei, locus coeruleus, hypothalamic and thalamic structures, putamen, nucleus accumbens, diagonal band nuclei and dentate gyrus, and in portions of the parietal, cingulate, insular, frontal and orbital cortex. In formalin‐injected rats, pretreated with anti‐β‐endorphin, behavioural changes indicative of hyperalgesia (increased licking response) were found, which were paralleled by a significant enhancement of functional activity in the anterior pretectal nucleus and in thalamo‐cortical systems. A positive correlation was found between the duration of the licking response and metabolic activity of several forebrain regions. These results provide a map of the CNS pattern of metabolic activity during tonic somatic pain, and demonstrate a modulatory role for β‐endorphin in central networks that process somatosensory inputs.
Episodic corticosterone treatment accelerates kindling epileptogenesis and triggers long‐term changes in hippocampal CA1 cells, in the fully kindled state
Authors: Karst Henk , De Kloet E. Ronald , Joëls Marian 
Published: March 2003

AbstractWe tested the effect of episodic (≈ 10 days) corticosterone treatment on: (i) behavioural symptoms during kindling epileptogenesis; and (ii) electrical activity in the CA1 hippocampal area during epileptogenesis, and later on, in the fully kindled state. Male rats received a corticosterone‐releasing pellet (100 mg/day) shortly before kindling was started, resulting in elevated hormone levels during the early and middle stages of epileptogenesis. The appearance of moderate behavioural signs of epilepsy and severe tonic–clonic seizures was significantly accelerated in corticosterone‐treated animals compared to placebo controls. During epileptogenesis, corticosterone treatment did not affect the amplitude and paired‐pulse characteristics of in vivo‐recorded CA1 field responses, or the duration of the afterdischarge following tetanic stimulation of the Schaffer collaterals. However, other properties of CA1 cells studied in vitro, in the fully kindled state, were altered by the earlier episodic corticosterone treatment. Thus, in kindled rats, the amplitude of the population spike in the CA1 area was significantly enhanced after prior exposure to high corticosterone levels. Prior episodic steroid treatment resulted furthermore in a significantly increased amplitude of voltage‐gated Ca currents, in kindled rats. At that time, corticosterone levels of animals which had received a corticosterone‐releasing pellet earlier were no longer elevated compared to the placebo controls; the corticosteroid‐treated rats did also not differ from the controls with respect to the mRNA expression levels for the two corticosteroid receptor subtypes in the hippocampus. The data suggest that exposure of animals to a period of stressful experiences during a critical phase in epileptogenesis could impose lasting deleterious effects on the course of epilepsy, even when CORT levels have been normalized again.
The close homologue of the neural adhesion molecule L1 (CHL1): patterns of expression and promotion of neurite outgrowth by heterophilic interactions
Authors: Hillenbrand Rainer , Molthagen Martin , Montag Dirk , Schachner Melitta 
Published: March 2003

AbstractThe close homologue of L1 (CHL1), a member of the L1 family of neural adhesion molecules, is first expressed at times of neurite outgrowth during brain development, and is detectable in subpopulations of neurons, astrocytes, oligodendrocyte precursors and Schwann cells of the mouse and rat. Aggregation assays with CHL1‐transfected cells show that CHL1 does not promote homophilic adhesion or does it mediate heterophilic adhesion with L1. CHL1 promotes neurite outgrowth by hippocampal and small cerebellar neurons in substrate‐bound and soluble form. The observation that CHL1 and L1 show overlapping, but also distinct patterns of synthesis in neurons and glia, suggests differential effects of L1‐like molecules on neurite outgrowth.
Organization of visual cortex in the northern quoll, Dasyurus hallucatus: evidence for a homologue of the second visual area in marsupials
Authors: Rosa Marcello G. P. , Krubitzer Leah A. , Molnár Zoltán , Nelson John E. 
Published: March 2003

AbstractTwo visual areas, V1 and V2 (first and second visual areas), appear to be present in the posterior neocortex of all eutherian mammals investigated so far. However, previous studies have not established whether an area homologous to V2 also exists in metatherian mammals (marsupials). Using electrophysiological techniques, we mapped the visual receptive fields of neurons in the striate and peristriate cortices of the northern quoll, an Australian marsupial. We found that neurons in a 2‐mm‐wide strip of cortex rostrolateral to V1 form a single, relatively simple representation of the complete contralateral hemifield. This area resembles V2 of eutherians in several respects: (i) neurons in the medial half of the peristriate area represent the lower visual quadrant, whereas those in the lateral half represent the upper visual quadrant; (ii) the vertical meridian of the visual field is represented adjacent to V1, while the visual field periphery is represented along the lateral and rostrolateral borders of the peristriate area; (iii) there is a marked anisotropy in the representation, with a larger magnification factor parallel to the V1 border than perpendicular to this border; and (iv) receptive fields of multiunit clusters in the peristriate cortex are much larger than those of cells in V1 at comparable eccentricities. The cortex immediately rostral and lateral to V2 did not respond to visual stimulation under our recording conditions. These results suggest that V1 and V2 together form a ‘core’ of homologous visual areas, likely to exist in all therian mammals.
c‐Jun expression after axotomy of corneal trigeminal ganglion neurons is dependent on the site of injury
Authors: De Felipe Carmen , Belmonte Carlos 
Published: March 2003

AbstractThe proto‐oncogene c‐Jun has been implicated in the control of neuronal responses to injury and in axonal growth during regenerative processes. We have investigated the expression of c‐Jun during normal terminal remodelling in trigeminal ganglion neurons innervating the cornea and after acute injury of epithelial nerve terminals or parent axons. Remodelling and rearrangement, or damage limited to corneal epithelium endings, was not a trigger for activation of c‐Jun expression. However, injury of parent axons in the stroma or in the orbital ciliary nerves induced c‐Jun expression in 50% of the population of corneal neurons, which included all of the large myelinated and 20% of the small neuropeptide‐containing corneal neurons. This suggests that c‐Jun expression in trigeminal ganglion neurons is not associated with normal remodelling or regeneration of peripheral nerve terminals, and that it takes place only when parent axons are injured. A substantial number of damaged neurons do not express c‐Jun, indicating that in primary sensory neurons, injury and regeneration may not always be coupled to the expression of this proto‐oncogene.
Neuropeptide Y increases intracellular calcium in rat pinealocytes
Authors: Simonneaux Valérie , Rodeau Jean‐Luc , Calgari Christiane , Pévet Paul 
Published: March 2003

AbstractThe pineal gland is mainly innervated by sympathetic fibres containing noradrenaline (NA) and neuropeptide Y (NPY). NA released at night stimulates melatonin synthesis via a β1‐adrenergic‐induced increase in cyclic adenosine monophosphate (cAMP) concentration potentiated by an α1‐adrenergic‐induced increase in Ca2+ concentration. We previously showed that NPY acted on presynaptic Y2 receptors inhibiting NA release and on postsynaptic Y1 receptors stimulating melatonin synthesis. Here we used Fura‐2 imaging to assess the effect of NPY on the intracellular Ca2+ concentration, [Ca2+]i, in cultured rat pineal cells. In 84% of cells, on average, 10 nm NPY induced a progressive rise of [Ca2+]i from its basal value of 102 ± 3 nm to a plateau of 180 ± 6 nm (n = 467 cells), which lasted the time of NPY application. This effect of NPY appeared dependent on extracellular Ca2+.
Suppression of epileptogenesis by modification of N‐methyl‐d‐aspartate receptor subunit composition
Authors: Bengzon Johan , Okabe Shigeo , Lindvall Olle , McKay Ronald D. G. 
Published: March 2003

AbstractThe effects of altered N‐methyl‐d‐aspartate (NMDA) receptor subunit composition on seizure development in kindling epilepsy were assessed in transgenic mice expressing high neuronal levels of NR2D under control of the calcium/calmodulin kinase II alpha subunit (αCaMKII) promoter. The NR2D subunit is normally present at very low levels in the mature forebrain. Transgenic mice showed a marked reduction of amygdala kindling development. Spread of epileptic activity was retarded and generalized seizures appeared later in animals overexpressing NR2D compared with wild‐type mice. The progressive lengthening of epileptiform activity, which normally occurs in kindling, was also dampened in transgenic animals. We conclude that NMDA receptor subunit composition determines the progression of experimental epilepsy.
Spatiotemporal patterning of glutamate receptors in developing ferret striate cortex
Authors: Smith Adam L. , Thompson Ian D. 
Published: March 2003

AbstractWe have studied glutamate receptor levels during very early phases of cortical formation by using quantitative in vitro autoradiography to map the expression of NMDA, AMPA and kainate receptors in the developing primary visual cortex of the ferret. NMDA and non‐NMDA receptors exhibit very different developmental profiles in primary visual cortex. NMDA receptor density is low at birth and increases throughout the first 2 postnatal months, rising between threefold (layers II/III) and ninefold (layer VI). In contrast, AMPA receptors are abundant at birth and their density remains constant for the first postnatal month, before rising by a maximum of 1.7‐fold (layer I) at around the time of eye‐opening (postnatal day 32). Kainate receptors are also present in high levels at birth and their expression levels rise in the early postnatal period by between 1.5‐fold (layer I) and threefold (layers V/VI) to a peak just after eye‐opening. The proportion of the total ionotropic glutamate receptor binding contributed by NMDA receptors thus rises from 5% at birth to a maximum of 22% at 2 months of age, while the AMPA receptor contribution falls from 87% to 72% over the same period. Below cortex, all three glutamate receptor subtypes are expressed in the subplate region for the first 3 postnatal weeks. These developmental patterns, combined with the fact that AMPA receptors are densely expressed in the proliferative zones underlying presumptive area 17, indicate that non‐NMDA receptor expression levels in primary visual cortex are mostly specified much earlier than those of NMDA receptors.
Ontogeny of water transport in rat brain: postnatal expression of the aquaporin‐4 water channel
Authors: Wen H. , Nagelhus E. A. , Amiry‐Moghaddam M. , Agre P. , Ottersen O. P. , Nielsen S. 
Published: March 2003

AbstractBrain water transport is poorly understood at the molecular level, and marked changes occur during brain development. As the aquaporin‐4 (AQP4) water channel protein is abundant in brain, the expression levels and subcellular distribution of this protein were examined during postnatal development. This study focused on the cerebellum, which showed the same pattern of AQP4 development as the rest of the brain. Semiquantitative immunoblotting revealed very low levels of AQP4 in the first postnatal week. A pronounced increase was noted in the second week, from 2% of adult level at postnatal day 7 (PN7) to 25% at PN14. At PN1 and PN3 immunofluorescence microscopy revealed weak labelling, mainly in radial processes (Bergmann fibres) and at the pial surface. Between PN7 and PN14 the labelling underneath the pia showed a strong increase, and immunoreactivity also appeared around blood vessels throughout the cerebellum. High‐resolution immunogold electron microscopy revealed that the subpial and perivascular labelling was restricted to glial end feet, notably to those plasma membrane domains that were apposed to the basal laminae. At no stage was there any evidence of neuronal AQP4 labelling, and AQP1, −2, −3 and −5 proteins were not detected in the neuropil. Riboprobes to AQP4 mRNA produced a particularly strong in situ hybridization signal in glial cells between PN7 and PN14, corresponding to the stage of the most rapid increase of AQP4 protein. The time course and pattern of AQP4 expression suggests that this aquaporin plays an important role in brain water and K+ homeostasis from the second week of development.
Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites
Authors: Guo A. , Vulchanova L. , Wang J. , Li X. , Elde R. 
Published: March 2003

AbstractThe vanilloid receptor (VR1) protein functions both as a receptor for capsaicin and a transducer of noxious thermal stimuli. To determine the expression and targetting of this protein, we have generated antisera against both the amino and carboxy termini of VR1. Within the dorsal root and trigeminal ganglia of rats, VR1‐immunoreactivity (VR1‐ir) was restricted to small and medium sized neurons. VR1‐ir was transported into both the central and peripheral processes of these primary afferent neurons, as evidenced by: (i) the presence of VR1‐ir in nerve fibres and terminals in lamina I and lamina II of the superficial dorsal horn, and the association of VR1‐ir with small diameter nerve fibres in the skin and cornea; (ii) the reduction of VR1‐ir in the spinal cord after dorsal rhizotomy; and (iii) the accumulation of VR1‐ir proximal to sciatic nerve ligation. At the ultrastructural level, VR1‐ir was associated with plasma membranes of neuronal perikarya in dorsal root ganglia and nerve terminals in the dorsal horn. VR1‐ir was also seen in nerve fibres and terminals in the spinal trigeminal nucleus and nucleus of the solitary tract. Within a large proportion of dorsal root ganglion neurons and the terminals of their axons, VR1‐ir was colocalized with staining for the P2X3 purinoceptor, and with binding sites for the lectin IB4. Surprisingly, VR1‐ir did not coexist substantially in nerve fibres and terminals that contain substance P and calcitonin gene‐related peptide, suggesting complex mechanisms for the release of these neuropeptides in response to capsaicin application.
Expression of Ras‐GRF in the SK‐N‐BE neuroblastoma accelerates retinoic‐acid‐induced neuronal differentiation and increases the functional expression of the IRK1 potassium channel
Authors: Tonini Raffaella , Mancinelli Enzo , Balestrini Monica , Mazzanti Michele , Martegani Enzo , Ferroni Arnaldo , Sturani Emmapaola , Zippel Renata 
Published: March 2003

AbstractRas‐GRF, a neuron‐specific Ras exchange factor of the central nervous system, was transfected in the SK‐N‐BE neuroblastoma cell line and stable clones were obtained. When exposed to retinoic acid, these clones showed a remarkable enhancement of Ras‐GRF expression with a concomitant high increase in the level of active (GTP‐bound) Ras already after 24 h of treatment. In the presence of retinoic acid, the transfected cells stopped growing and acquired a differentiated neuronal‐like phenotype more rapidly than the parental ones. Cells expressing Ras‐GRF also exhibited a more hyperpolarized membrane potential. Moreover, treatment with retinoic acid led to the appearance of an inward rectifying potassium channel with electrophysiological properties similar to IRK1. This current was present in a large number of cells expressing Ras‐GRF, while only a small percentage of parental cells exhibited this current. However, Northern analysis with a murine cDNA probe indicated that IRK1 mRNA was induced by retinoic acid at a similar level in both kinds of cells. Brief treatment with a specific inhibitor of the mitogen‐activated protein kinase (MAPK) pathway reduced the number of transfected cells showing IRK1 activity. These findings suggest that activation of the Ras pathway accelerates neuronal differentiation of this cell line. In addition, our results suggest that Ras‐GRF and/or Ras‐pathway may have a modulatory effect on IRK1 channel activity.