bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex regulation of the expression of the polysialylated form of the neuronal cell adhesion molecule by glucocorticoids in the rat hippocampus
Authors: Rodriguez J. J. , Montaron M. F. , Petry K. G. , Aurousseau C. , Marinelli M. , Premier S. , Rougon G. , Moal M. Le , Abrous D. N. 
Published: March 2003

AbstractThe gyrus dentatus is one of the few areas of the brain that continues to produce neurons after birth. The newborn cells differentiate into granule cells which project axons to their postsynaptic targets. This step is accompanied by the transient expression of the polysialylated isoforms of neuronal cell adhesion molecules (PSA‐NCAM) by the developing neurons. Glucocorticoid hormones have been shown to inhibit neurogenesis. We noted a functional correlation between PSA‐NCAM expression and glucocorticoid action after manipulation of corticosterone levels in the adrenalectomized rat. Adrenalectomy increased neurogenesis, evaluated from the incorporation of 5‐bromo‐2′‐deoxyuridine in neuronal precursors, as well as PSA‐NCAM expression. The increase in PSA‐NCAM‐immunoreactive (IR) cells in the gyrus dentatus, evidenced 72 h following adrenalectomy, persisted for at least a month. It was accompanied by enhanced dendritic arborization of PSA‐NCAM‐IR cells in the gyrus dentatus and by an increase in number of PSA‐NCAM‐IR fibres in the CA3 subfield. Neurogenesis was normalized by restitution of diurnal or nocturnal levels of corticosterone, whereas normalization of PSA‐NCAM expression was only observed after simulation of the complete circadian fluctuation of the hormone. Our findings reveal the complex action of corticosterone in modulating the expression of PSA‐NCAM in the gyrus dentatus of the hippocampal formation. They also highlight the importance of corticosterone fluctuations in the control of neurogenesis and plasticity in this structure.
The neuronal death induced by endotoxic shock but not that induced by excitatory amino acids requires TNF‐α
Authors: De Bock Frédéric , Derijard Benoît , Dornand Jacques , Bockaert Joël , Rondouin Gérard 
Published: March 2003

AbstractWe studied, using organotypic hippocampal slices in culture, the role of pro‐inflammatory cytokines, oxygen radicals and nitric oxide in neuronal death induced either by endotoxic insult [interferon (IFN) γ, 24 h followed by lipopolysaccharide, 24 h] or by glutamate receptor‐mediated excitotoxic insult. We demonstrated that neuronal death induced by endotoxic insult was absolutely dependent on the synthesis of tumour necrosis factor alpha (TNF‐α). Indeed, TNF‐α antibodies and SB203580, an inhibitor of p38 stress kinase known to block TNF‐α and other cytokine synthesis, completely protected neurons from the endotoxic insult. Inhibiting oxygen radical and nitric oxide productions also reduced the endotoxic shock. We also showed that after priming the cultures with IFN‐γ, TNF‐α was unable to induce neuronal death unless oxygen‐free radicals were exogenously provided. In contrast, although glutamate receptor‐induced excitotoxicity was associated with a low TNF‐α synthesis and a modest activation of p38 stress kinase, neither TNF‐α antibodies nor SB203580 were able to decrease excitotoxic neuronal insult. We did not reduce glutamate receptor‐induced neuronal death with superoxide dismutase plus catalase. In conclusion, although inflammation follows glutamate receptor‐mediated neurotoxicity, the mechanisms by which an endotoxic insult triggers neuronal death are different from those involved in excitotoxicity.
Modulation by substance P of synaptic transmission in the mouse hippocampal slice
Authors: Kouznetsova Maria , Nistri Andrea 
Published: March 2003

AbstractThe modulatory action of substance P on synaptic transmission of CA1 neurons was studied using intra‐ or extracellular recording from the mouse hippocampal slice preparation. Bath‐applied substance P (2–4 μm) or the selective NK1 receptor agonist substance P methylester (SPME, 10 nm–5 μm) depressed field potentials (recorded from stratum pyramidale) evoked by focal stimulation of Schaffer collaterals. This effect was apparently mediated via NK1 receptors since it was completely blocked by the selective NK1 antagonist SR 140333. The field potential depression by SPME was significantly reduced in the presence of bicuculline. Intracellular recording from CA1 pyramidal neurons showed that evoked excitatory postsynaptic potentials (EPSPs) and evoked inhibitory postsynaptic potentials (IPSPs) were similarly depressed by SPME, which at the same time increased the frequency of spontaneous GABAergic events and reduced that of spontaneous glutamatergic events. The effects of SPME on spontaneous and evoked IPSPs were prevented by the ionotropic glutamate receptor blocker kynurenic acid. In tetrodotoxin (TTX) solution, no change in either the frequency of spontaneous GABAergic and glutamatergic events or in the amplitude of responses of pyramidal neurons to 4 μmα‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) or 10 μmN‐methyl‐d‐aspartate (NMDA) was observed. On the same cells, SPME produced minimal changes in passive membrane properties unable to account for the main effects on synaptic transmission. The present data indicate that SPME exerted its action on CA1 pyramidal neurons via a complex network mechanism, which is hypothesized to involve facilitation of a subset of GABAergic neurons with widely distributed connections to excitatory and inhibitory cells in the CA1 area.
Long‐ but not medium‐term retention of olfactory memories in honeybees is impaired by actinomycin D and anisomycin
Authors: Wüstenberg Daniel , Gerber Bertram , Menzel Randolf 
Published: March 2003

AbstractAlthough work in a wide variety of species and paradigms has demonstrated that long‐term memory is sensitive to the blocking of protein synthesis, previous studies have suggested that the honeybee might represent an exception to this rule. Retention tested one day after training was not impaired by the inhibition of translation by cycloheximide. Using blockers of either transcription (actinomycin D) or translation (anisomycin), we present experiments that reconcile this unusual finding by testing over longer retention periods. Honeybees were conditioned to associate an odourant with a sucrose reward. Typically, this leads to stable retention over days. However, injection of either drug led to lower retention after 4 days, whereas retention after 2 or sometimes even 3 days was unaffected. This dissociates two forms of memory: a protein synthesis‐independent, medium‐term memory (up to 3 days) and a protein synthesis‐dependent, long‐term memory lasting for at least 4 days.
A minigene of neural agrin encoding the laminin‐binding and acetylcholine receptor‐aggregating domains is sufficient to induce postsynaptic differentiation in muscle fibres
Authors: Meier Thomas , Marangi P. Angelo , Moll Joachim , Hauser Dominik M. , Brenner Hans‐R. , Ruegg Markus A. 
Published: March 2003

AbstractThe extracellular matrix molecule agrin is both necessary and sufficient for inducing the formation of postsynaptic specializations at the neuromuscular junction (NMJ). At the mature NMJ, agrin is stably incorporated in synaptic basal lamina. The postsynapse‐inducing activity of chick agrin, as assayed by its capability of causing aggregation of acetylcholine receptors (AChRs) on cultured muscle cells, maps to a 21 kDa, C‐terminal domain. Binding of chick agrin to muscle basal lamina is mediated by the laminins and maps to a 25 kDa, N‐terminal fragment of agrin. Here we show that an expression construct encoding a ‘mini’‐agrin, in which the laminin‐binding fragment was fused to the AChR‐clustering domain, is sufficient to induce postsynaptic differentiation in vivo when injected into non‐synaptic sites of rat soleus muscle. As shown for ectopic postsynaptic differentiation induced by full‐length neural agrin, myonuclei underneath the ectopic sites expressed the gene for the AChR ε‐subunit. Altogether, our data show that a ‘mini’‐agrin construct encoding only a small fraction of the entire agrin protein is sufficient to induce postsynapse‐like structures that are reminiscent of those induced by full‐length neural agrin or innervation by motor neurons.
Neurochemical characterization of individual vulnerability to addictive drugs in rats
Authors: Lucas Louis R. , Angulo Jesus A. , Moal Michel Le , McEwen Bruce S. , Piazza Pier V. 
Published: March 2003

AbstractRats exposed to a low‐light, low‐noise, novel environment exhibit differences in individual locomotor response to the novelty stressor. The categorization of rats in a locomotor screening procedure as low‐ (LR) or high‐responders (HR), where LRs are in the low locomotor range while HRs belong to the high locomotor range, is significant in that HRs show higher activity in mesencephalic dopaminergic projection neurons, and also show a higher propensity to self‐administer psychostimulants and other drugs of abuse compared with LRs. In this study, we examined the neurobiological basis of dopaminergic hyperactivity by comparing in HRs and LRs the steady‐state differences in regulatory inputs to mesencephalic (substantia nigra and ventral tegmental area: VTA) dopaminergic neurons. In particular, using in situ hybridization, we studied levels of mRNA for tyrosine hydroxylase (TH) and cholecystokinin (CCK) in the mesencephalon, and for preprodynorphin (DYN), preproenkephalin (PPE), and preprotachykinin (PPT) in the striatum and nucleus accumbens (Acb). We also evaluated TH levels by radioimmunocytochemistry (TH‐RIC) in striatal, accumbal and mesencephalic regions. HRs versus LRs had lower levels of neurochemicals belonging to the intrinsic inhibitory input to dopaminergic neurons in the VTA, e.g. lower TH‐RIC (–25%) and CCK‐mRNA (–48%). In contrast, HRs showed higher levels of parameters belonging to extrinsic facilitating inputs, e.g. higher PPE‐mRNA (+ 37%). In addition, HRs had higher DYN‐mRNA in Acb (+ 61%), which has been shown to be positively correlated with higher dopaminergic activity. These results enhance our knowledge of the neurobiological correlates of individual rats' propensities to develop drug‐intake and provide some putative mechanisms for the dopaminergic hyperactivity that characterizes drug‐prone animals.
Characterization of neuronal migration disorders in neocortical structures: quantitative receptor autoradiography of ionotropic glutamate, GABAA and GABAB receptors
Authors: Zilles Karl , Qü Meishu , Schleicher Axel , Luhmann Heiko J. 
Published: March 2003

AbstractEpileptiform activity was previously described [Luhmann et al. (1998) Eur.J. Neurosci., 10, 3085–3094] in the neocortex of the adult rat following freeze lesioning of the newborn neocortex. After a survival time of 3 months, a small area of dysplastic cortex surrounded by histologically normal (exofocal) neocortex was observed. The dysplastic cortex is characterized by the formation of a small sulcus and a three‐ to four‐layered architecture. Two questions are addressed here: (i) is the hyperexcitability associated with changes in binding to major excitatory and inhibitory transmitter receptors in the dysplastic cortex?; and (ii) do such changes also occur in the exofocal cortex?  Alterations in binding to glutamatergic N‐methyl‐d‐aspartate (NMDA), (±)‐α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA), kainate and GABAA and GABAB (γ‐aminobutyric acid) receptors are demonstrated with quantitative in vitro receptor autoradiography by using the ligands [3H]MK‐801, [3H]AMPA, [3H]kainate, [3H]muscimol and [3H]baclofen, respectively. In the dysplastic cortex, the binding to NMDA, AMPA and kainate receptors is significantly increased, whereas the binding to GABAA and GABAB receptors is reduced. Exofocal areas of the lesioned hemisphere show an imbalance between excitatory and inhibitory receptor binding with an up‐regulation of the binding to AMPA and kainate, and a down‐regulation to GABAA receptors. The binding to GABAB and NMDA receptors is not significantly changed in the exofocal areas.  The imbalance between excitatory and inhibitory receptors may cause the hyperexcitability, as previously found in the identical experimental model, and may also induce epileptiform activity in the human cortex with migration disorders.
Calcium electrogenesis in neocortical pyramidal neurons in vivo
Authors: Paré Denis , Lang Eric J. 
Published: March 2003

AbstractMuch of what is known about Ca2+ electrogenesis in neocortical cells has been derived from in vitro studies. Since Ca2+ currents are controlled by various modulators, comparing these findings to in vivo data is essential. Here, we analysed tetrodotoxin (TTX)‐resistant, presumably Ca2+‐mediated potentials in intracellularly recorded neocortical neurons in vivo. TTX was applied locally to block Na+ channels. Its effectiveness was demonstrated by the elimination of fast spikes and orthodromic responses. In response to depolarizing current pulses bringing the membrane potential beyond ≈–33 mV, 71% of neurons generated high‐threshold Ca2+ spikes averaging 17 mV. This is in contrast with in vitro findings, where high‐threshold spikes could only be elicited following the blockade of K+ conductances. Consistent with this, neurons dialysed with K+ channel blockers in vivo generated high‐threshold spikes that had a lower threshold (≈–40 mV) and, with intracellular Cs+, a larger amplitude, indicating the presence of K+ currents opposing the activation of Ca2+ channels. Only 15% of cortical cells displayed low‐threshold Ca2+ spikes. To compare high‐threshold Ca2+ spikes evoked by synaptic stimuli or current injection, another group of cortical neurons was dialysed with QX‐314 and Cs+, in the absence of extracellular TTX. Synaptic stimuli applied on a background of membrane depolarization elicited presumed Ca2+ spikes whose amplitude varied in a stepwise fashion. Thus, although there are numerous similarities between in vivo and in vitro data, some significant differences were found, which suggest that the high‐voltage activated Ca2+ currents and/or the K+ conductances that oppose them are subjected to different modulatory influences in vivo than in vitro.
Transforming growth factor‐β mediates the neurotrophic effect of fibroblast growth factor‐2 on midbrain dopaminergic neurons
Authors: Krieglstein Kerstin , Reuss Bernhard , Maysinger Dusica , Unsicker Klaus 
Published: March 2003

AbstractFibroblast growth factor (FGF)‐2 is an established neurotrophic factor for dopaminergic (DAergic) neurons in the ventral midbrain. Its survival and differentiation‐promoting effects on DAergic neurons in vitro and in vivo are crucially dependent on the presence, numerical expansion and maturation of astroglial cells. We show now that transforming growth factor (TGF)‐β, an established trophic factor for DAergic neurons and product of astroglial cells, mediates the trophic effect of FGF‐2 on DAergic neurons cultured from the embryonic rat midbrain floor. Antibodies to TGF‐β that neutralize the isoforms ‐β1, ‐β2 and ‐β3 abolish the trophic effect of FGF‐2. FGF‐2 increases TGF‐β3 mRNA and amounts of biologically active TGF‐β determined in a mink lung epithelial cell assay in a time‐dependent manner. FGF‐2 also induces levels of active TGF‐β in neonatal rat astrocytes cultured from midbrain, striatum and cortex. We conclude that TGF‐β is required for mediating the survival promoting effect of FGF‐2 on DAergic and, possibly, cortical and striatal neurons grown in the presence of glial cells.
Protection of axotomized retinal ganglion cells by adenovirally delivered BDNF in vivo
Authors: Isenmann Stefan , Klöcker Nikolaj , Gravel Claude , Bähr Mathias 
Published: March 2003

AbstractFollowing intraorbital transection of the optic nerve (ON) in rats, more than 80% of the retinal ganglion cell (RGC) population die by apoptosis within 14 days. Repeated intraocular injection of brain‐derived neurotrophic factor (BDNF) has been efficient in enhancing RGC survival following ON axotomy. The present study was designed to define a potential survival‐promoting effect of adenovirally administered BDNF on axotomized RGCs. A single injection of an adenoviral vector expressing the human BDNF gene from a CMV promoter/enhancer (Ad‐BDNF) enhanced RGC survival 14 days after axotomy by 40.3%. Moreover, a combinatory treatment regimen consisting of intraocular Ad‐BDNF administration and systemic application of the free radical scavenger, N‐tert‐butyl‐(2‐sulphophenyl)‐nitrone (S‐PBN), enhanced RGC survival by 63.0%. Our data demonstrate that adenoviral delivery of neurotrophic factors to the vitreous body is a feasible approach for the prevention of axotomy‐induced RGC death. Further, as shown for S‐PBN, therapeutic regimens that combine local virus‐mediated gene delivery with systemic administration of protective compounds, may offer promising strategies for future treatment also in human neurodegenerative conditions.
BDNF and NT‐3 applied in the whisker pad reverse cortical changes after peripheral deafferentation in neonatal rats
Authors: Calia Eustachio , Persico Antonio M. , Baldi Alfonso , Keller Flavio 
Published: March 2003

AbstractIt has been known for a long time that subcortical input drives the specification of cortical areas. Molecular signals mediating this instructive effect from the periphery are poorly understood. In foetal or neonatal rats, ablation of whisker follicles, transection of the infraorbital nerve, inhibition of axonal transport, but not impulse activity blockade, prevent formation of barrels in the primary somatosensory cortex (S1). These findings suggest that a chemical signal, possibly arising from the skin or the follicle, may be responsible for somatotopic pattern formation in S1. Neurotrophins promote survival and differentiation of primary sensory neurons, and are expressed in the whisker pad during development. Neonatal rats received gelfoam impregnated with NGF, BDNF or NT‐3 under the whisker pad following surgical denervation of whisker rows D and E on P0. Barrel formation in S1 was assessed on P7 by acetylcholinesterase histochemistry and 5‐HT‐immunohistochemistry. BDNF and NT‐3, but not NGF, promoted development of the cortical barrels corresponding to denervated whiskers. Furthermore, BDNF and NT‐3 prevented the lesion‐induced expansion of row C barrels, while NGF appeared to promote row C expansion. Our results suggest that BDNF and NT‐3 arising from the whisker pad are involved in the formation and/or maintenance of the barrel pattern in S1. These findings are potentially relevant for the prevention of sensory disturbances possibly due to reorganization of central sensory circuits after peripheral nerve lesions in humans.
A visuo‐somatomotor pathway through superior parietal cortex in the macaque monkey: cortical connections of areas V6 and V6A
Authors: Shipp S. , Blanton M. , Zeki S. 
Published: March 2003

AbstractThis report addresses the connectivity of the cortex occupying middle to dorsal levels of the anterior bank of the parieto‐occipital sulcus in the macaque monkey. We have previously referred to this territory, whose perimeter is roughly circumscribed by the distribution of interhemispheric callosal fibres, as area V6, or the ‘V6 complex’. Following injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA‐HRP) into this region, we examined the laminar organization of labelled cells and axonal terminals to attain indications of relative hierarchical status among the network of connected areas. A notable transition in the laminar patterns of the local, intrinsic connections prompted a sub‐designation of the V6 complex itself into two separate areas, V6 and V6A, with area V6A lying dorsal, or dorsomedial to V6 proper. V6 receives ascending input from V2 and V3, ranks equal to V3A and V5, and provides an ascending input to V6A at the level above. V6A is not connected to area V2 and in general is less heavily linked to the earliest visual areas; in other respects, the two parts of the V6 complex share similar spheres of connectivity. These include regions of peripheral representation in prestriate areas V3, V3A and V5, parietal visual areas V5A/MST and 7a, other regions of visuo‐somatosensory association cortex within the intraparietal sulcus and on the medial surface of the hemisphere, and the premotor cortex. Subcortical connections include the medial and lateral pulvinar, caudate nucleus, claustrum, middle and deep layers of the superior colliculus and pontine nuclei.  From this pattern of connections, it is clear that the V6 complex is heavily engaged in sensory‐motor integration. The specific somatotopic locations within sensorimotor cortex that receive this input suggest a role in controlling the trunk and limbs, and outward reaching arm movements. There is a secondary contribution to the brain's complex oculomotor circuitry. That the medial region of the cortex is devoted to tightly interconnected representations of the sensory periphery, both visual and somatotopic—which are routinely stimulated in concert—would appear to be an aspect of the global organization of the cortex which must facilitate multimodal integration.
Organization of projections of rat retrosplenial cortex to the anterior thalamic nuclei
Authors: Shibata Hideshi 
Published: March 2003

AbstractThe organization of the projections from the retrosplenial cortex (Brodmann's area 29) to the anterior thalamic nuclei was examined in the rat with retrograde transport of the cholera toxin B subunit and anterograde transport of biotinylated dextran amine. Areas 29a and 29b project mainly ipsilaterally to the rostral two‐thirds of the anteroventral nucleus, with area 29a projecting more rostrodorsally than area 29b. Area 29c projects bilaterally to the ventromedial part of the anteroventral nucleus. The projections from area 29c are organized in a topographic pattern such that the rostral area 29c projects to the caudoventral part of the anteroventral nucleus, whereas the caudal area 29c projects to the more rostrodorsal parts. Caudal area 29d projects mainly ipsilaterally to the rostrodorsal part of the anteromedial nucleus, and the rostral and dorsal parts of the anteroventral nucleus, whereas rostral area 29d projects bilaterally to the caudodorsal part of the anteromedial nucleus and the caudolateral part of the anteroventral nucleus. All the areas of the retrosplenial cortex provide sparse projections, mainly ipsilateral, to the anterodorsal nucleus, with a crude topographic pattern such that the rostrocaudal axis of the retrosplenial cortex corresponds to the caudorostral axis of the anterodorsal nucleus. The results indicate that each area of the retrosplenial cortex has a distinct projection field within the anterior thalamic nuclei. This suggests that each of these projections transmits distinct information that is important for complex memory and learning functions, e.g. discriminative avoidance learning and spatial memory.