bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain inflammatory reaction in an animal model of neuronal degeneration and its modulation by an anti‐inflammatory drug: implication in Alzheimer's disease
Authors: Scali Carla , Prosperi Costanza , Vannucchi Maria Giuliana , Pepeu Giancarlo , Casamenti Fiorella 
Published: March 2003

AbstractBrain inflammatory processes underlie the pathogenesis of Alzheimer's disease, and nonsteroidal anti‐inflammatory drugs have a protective effect in the disease. The aim of this study was to characterize in vivo in the rat brain the inflammatory reaction in response to excitotoxic insult and to investigate the efficacy of nimesulide treatment. Quisqualic acid was injected into the right nucleus basalis of rats. The excitotoxin induced cholinergic degeneration, an intense glial reaction and the production of inflammatory mediators. Three hours after injection, a five‐fold elevation in the concentration of interleukin‐1β in the injected area was observed. This elevation was reduced by 50% by nimesulide (10 mg/kg, i.m.) pretreatment. Electron microscope examination and immunocytochemical staining revealed an intense activation of microglia and astrocytes at both 24 h and 7 days after injection. Cyclooxygenase‐2‐immunoreactivity was induced in the blood vessels of the injected hemisphere in perivascular microglial and endothelial cells 24 h after injection. Seven days postinjection, a cyclooxygenase‐2‐positive signal was induced in the parenchymal microglia and large amounts of prostaglandin‐E2 were measured in the injected area. Twenty‐four hours and 7 days after injection, many inducible nitric oxide synthase‐positive cells and a high level of nitrite were detected at the injection site. Seven days of nimesulide (10 mg/kg/day, i.m.) treatment strongly attenuated the microglial reaction, reduced the number of inducible nitric oxide synthase‐positive cells and completely abolished the increase in prostaglandin‐E2 formation. These data provide valuable support in vivo for the potential efficacy of cyclooxygenase‐2 inhibitors in Alzheimer's disease therapy.
Syntaxin 13 is a developmentally regulated SNARE involved in neurite outgrowth and endosomal trafficking
Authors: Hirling Harald , Steiner Pascal , Chaperon Catherine , Marsault Robert , Regazzi Romano , Catsicas Stefan 
Published: March 2003

AbstractIn addition to its role in exocytosis, SNAP‐25 is essential for axonal outgrowth. In order to identify SNARE proteins involved in neurite growth we have used SNAP‐25 antibodies to affinity‐purify protein complexes enriched in developing rat brain membrane extracts. We have identified a complex between SNAP‐25 and syntaxin 13 predominantly present in brain at embryonic or early postnatal stages. We show that syntaxin 13 is developmentally regulated with a decrease in adult brain. In differentiated neuroendocrine PC12 cells as well as primary cortical neurons the protein is localized to a punctated and tubular staining in the perinuclear region and along processes with high levels in the central region of growth cones. Carboxy‐terminally tagged syntaxin 13 was also detected on the plasma membrane by in vivo surface‐labelling where it colocalized with SNAP‐25. Syntaxin 13 has recently been shown to be implicated in early endosomal trafficking. In our study, colocalization with internalized transferrin in the cell body and along neurites confirmed endosomal location in both compartments. Finally, overexpression of full‐length syntaxin 13 enhanced neurite outgrowth in NGF‐stimulated PC12 cells, whilst it had no effect on regulated secretion. The data suggest that a syntaxin 13‐dependent endocytic trafficking step plays a limiting role in membrane expansion during neuronal development.
Basal forebrain neurons suppress amygdala kindling via cortical but not hippocampal cholinergic projections in rats
Authors: Ferencz I. , Leanza G. , Nanobashvili A. , Kokaia M. , Lindvall O. 
Published: March 2003

AbstractIntraventricular administration of the immunotoxin 192 IgG‐saporin in rats has been shown to cause a selective loss of cholinergic afferents to the hippocampus and cortical areas, and to facilitate seizure development in hippocampal kindling. Here we demonstrate that this lesion also accelerates seizure progression when kindling is induced by electrical stimulations in the amygdala. However, whereas intraventricular 192 IgG‐saporin facilitated the development of the initial stages of hippocampal kindling, the same lesion promoted the late stages of amygdala kindling. To explore the role of various parts of the basal forebrain cholinergic system in amygdala kindling, selective lesions of the cholinergic projections to either hippocampus or cortex were produced by intraparenchymal injections of 192 IgG‐saporin into medial septum/vertical limb of the diagonal band or nucleus basalis, respectively. Cholinergic denervation of the cortical regions caused acceleration of amygdala kindling closely resembling that observed after the more widespread lesion induced by intraventricular 192 IgG‐saporin. In contrast, removal of the cholinergic input to the hippocampus had no effect on the development of amygdala kindling. These data indicate that basal forebrain cholinergic neurons suppress kindling elicited from amygdala, and that this dampening effect is mediated via cortical but not hippocampal projections.
Polysorbate‐80 coating enhances uptake of polybutylcyanoacrylate (PBCA)‐nanoparticles by human and bovine primary brain capillary endothelial cells
Authors: Ramge Peter , Unger Ronald E. , Oltrogge Jens B. , Zenker Dietmar , Begley David , Kreuter Jörg , Von Briesen Hagen 
Published: March 2003

AbstractCertain drugs such as dalargin, loperamide or tubocurarine are not transported across the blood–brain barrier (BBB) and therefore exhibit no effects on the central nervous system. However, effects on the central nervous system can be observed when these drugs are loaded onto polybutylcyanoacrylate (PBCA)‐nanoparticles and coated with polysorbate 80. The mechanism by which these complexed nanoparticles cross the BBB and exhibit their effects has not been elucidated. Cultured microvessel brain endothelial cells of human and bovine origin were used as an in vitro model for the BBB to gain further insight into the mechanism of uptake of nanoparticles. With cells from these species we were able to show that polysorbate 80‐coated nanoparticles were taken up by brain endothelial cells much more rapidly and in significantly higher amounts (20‐fold) than uncoated nanoparticles. The process of uptake was followed by fluorescence and confocal laser scanning microscopy. The results demonstrate that the nanoparticles are taken up by cells and that this uptake occurs via an endocytotic mechanism.
Local GABAergic modulation of acetylcholine release from the cortex of freely moving rats
Authors: Giorgetti Marco , Bacciottini Lucia , Giovannini Maria Grazia , Colivicchi Maria Alessandra , Goldfarb Joseph , Blandina Patrizio 
Published: March 2003

AbstractCortical perfusion with GABA agonists and antagonists modulates the spontaneous release of cortical acetylcholine and GABA in freely moving rats. Twenty‐four hours after implantation of a dialysis fibre, cerebral cortex spontaneously released acetylcholine (3.8 ± 0.2 pmol/10 min) and GABA (6.6 ± 0.4 pmol/10 min) at a stable rate. Local administration of GABA (1 or 5 mm) or the GABAA agonist muscimol (25 or 50 μm) had no effect on the spontaneous release of acetylcholine. However, bicuculline (1–25 μm), a GABAA antagonist, added to the dialysis perfusate, elicited a concentration‐dependent increase of acetylcholine release to approximately double that of control. This effect of bicuculline (25 μm) was completely prevented by coperfusion with muscimol (50 μm). Local administration of the GABAB receptor agonist baclofen (10 or 50 μm) elicited a concentration‐dependent increase in spontaneous acetylcholine release with a maximal increase of about 60%. Intracortical administration of baclofen also decreased the spontaneous release of GABA. The GABAB receptor antagonist CGP 35348 (1 mm), administered alone for 20 min through the dialysis fibre, was without effect on spontaneous acetylcholine release; however, it completely blocked both the baclofen‐induced increase in acetylcholine release and the decrease in GABA release. These results suggest that cortically released GABA exerts a tonic influence on cholinergic activity.
Modulation of synaptic transmission in the rat ventral septal area by the pharmacological activation of metabotropic glutamate receptors
Authors: Tolchard Stephen , Clarke Geoff , Collingridge Graham L. , Fitzjohn Stephen M. 
Published: March 2003

AbstractThe ventral septal area (VSA) is considered to be critically involved in the control of the height and duration of fever. The major excitatory input to this region of the brain is glutamatergic, and the aim of this study was to investigate possible modulation of this synapse by metabotropic glutamate (mGlu) receptors. Whole‐cell patch recordings were made from individual VSA neurons voltage‐clamped at −60 mV. Activation of either group I or group II mGlu receptors (by bath application of 3,5‐dihydroxyphenylglycine (DHPG) or (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine (DCG‐IV), respectively) produced a long‐lasting depression of synaptic transmission which in both cases was insensitive to the N‐methyl‐ d‐aspartate (NMDA) receptor antagonist D‐2‐amino‐5‐phosphonopentanoate (D‐AP5). In contrast, application of (S)‐2‐amino‐4‐phosphonobutyric acid (L‐AP4), a group III mGlu receptor agonist, had a biphasic effect on synaptic transmission in the VSA, first eliciting a transient depression of transmission during drug application, followed by a marked and sustained potentiation of synaptic transmission upon drug washout. The response elicited by L‐AP4 was dependent on NMDA receptor activation, as in the presence of D‐AP5 the potentiation was replaced by an underlying long‐term depression (LTD) of transmission. These data provide the first evidence that metabotropic glutamate receptor agonists can induce both NMDA receptor‐dependent and ‐independent modulation of synaptic transmission in the VSA.
Increased responsivity of glutamate release from the substantia nigra pars reticulata to striatal NMDA receptor blockade in a model of Parkinson's disease. A dual probe microdialysis study in hemiparkinsonian rats
Authors: Marti M. , Sbrenna S. , Fuxe K. , Bianchi C. , Beani L. , Morari M. 
Published: March 2003

AbstractDual probe microdialysis was employed in freely moving 6‐hydroxydopamine (6‐OHDA) hemilesioned rats to investigate the effects of blockade of N‐methyl‐D‐aspartate (NMDA) receptors in the dorsolateral striatum on glutamate (Glu) release from the ipsilateral substantia nigra pars reticulata (SNr). Perfusion for 60 min with the NMDA antagonist dizocilpine (0.1 and 1 μm) in the dopamine (DA)‐denervated striatum stimulated nigral Glu release (peak effect of 139 ± 7% and 138 ± 9%, respectively). The lower (0.01 μm) and higher (10 μm) concentrations were ineffective. In sham‐operated rats, dizocilpine failed to affect nigral Glu release up to 1 μm but induced a prolonged stimulation at 10 μm (153 ± 9% at the end of perfusion). The present results show that DA‐deficiency in the striatum of hemiparkinsonian rats is associated with increased responsivity of nigral Glu release to striatal NMDA receptor blockade. This suggests that changes of NMDA receptor mediated control of the striatofugal pathways occur during Parkinson's disease (PD).
Organization of connections of the basal and accessory basal nuclei in the monkey amygdala
Authors: Bonda Eva 
Published: March 2003

AbstractThe present study investigated the intrinsic connections of the basal and accessory basal nuclei of the Macaca fascicularis monkey by means of the anterograde tracers Phaseolus vulgaris‐leucoagglutinin (PHA‐L) and biotinylated dextran amine (BDA). Analysis of the intranuclear connections of the basal nucleus indicates that there are five modules: dorsal, intermediate, ventral lateral, ventral medial and periamygdaloid sulcal cortex. The dorsal division projects to the intermediate division. Laterally, the intermediate division projects to the ventral lateral division and dorsal parts of the ventral medial division. Ventrally, the ventral lateral division projects to the ventral medial division and periamygdaloid sulcal cortex, which appears to constitute a medial extension of the basal nucleus onto the cortical surface of the amygdala. Medially, the ventral medial division projects to the intermediate and dorsal divisions. Thus, the connections between these modules form functional microcolumns within the nucleus with distinct patterns of information flow that are dorsal to ventral laterally, lateral to medial ventrally, and ventral to dorsal medially. Observations on the intranuclear connections of the accessory basal nucleus suggest that they are organized into two relatively distinct domains: the dorsal division projects to the ventral division and the ventral division projects primarily to the ventromedial division. Projections to other amygdaloid areas originate in select divisions of the basal and accessory basal nuclei, and are topographically distributed. The organization of intrinsic connections of the basal nuclei correlates with specific amygdalo‐cortical connections and suggests that extensive convergence of information takes place within the amygdala, which potentially influences activity at both the temporal and parietal pathways and hippocampal fields.
Suppression of the rat microglia Kv1.3 current by src‐family tyrosine kinases and oxygen/glucose deprivation
Authors: Cayabyab Francisco S , Khanna Rajesh , Jones Owen T , Schlichter Lyanne C 
Published: March 2003

AbstractMicroglia activate following numerous acute insults to the brain, including oxygen/glucose deprivation (OGD), and both protein tyrosine kinases (PTKs) and K+ channels have been implicated in their activation. We identified Kv1.3 (voltage‐gated potassium channel) protein in cultured rat microglia and confirmed that the native current is biophysically and pharmacologically similar to Kv1.3. To explore whether src‐family PTKs regulate the microglial Kv current, we first heterologously expressed Kv1.3 in a microglia‐like cell line derived from neonatal rat brain (MLS‐9). The resulting large Kv1.3 current was eliminated by co‐transfecting the constitutively active PTK, v‐src, then rapidly restored by the PTK inhibitor, lavendustin A. Acute activation of endogenous src kinases by a peptide activator significantly reduced the current, an effect that was mimicked by OGD. Similarly, in primary cultures of rat microglia, the endogenous Kv1.3‐like current was inhibited by activating endogenous src‐family PTKs and by OGD. Biochemical analysis showed that OGD increased the tyrosine phosphorylation of native Kv1.3 protein, which was alleviated by PTK inhibitors or reactive oxygen species (ROS) scavengers. Conversely, the basal level of Kv1.3 phosphorylation was decreased by PTK inhibitors or scavengers of ROS. Together, our results point to a post‐insertional downregulation of the microglial Kv1.3‐like current by oxidative stress and tyrosine phosphorylation. This interaction may be facilitated by a multiprotein complex because, in cultured microglia, the endogenous Kv1.3 and src proteins both bind to the scaffolding protein, post‐synaptic density protein 95 (PSD‐95). By associating with, and phosphorylating Kv1.3, src is well positioned to regulate microglial responses to oxidative stress.
A new class of neurotoxin from wasp venom slows inactivation of sodium current
Authors: Sahara Yoshinori , Gotoh Masamichi , Konno Katsuhiro , Miwa Akiko , Tsubokawa Hiroshi , Robinson Hugh P. C. , Kawai Nobufumi 
Published: March 2003

AbstractThe effects of α‐pompilidotoxin (α‐PMTX), a new neurotoxin isolated from the venom of a solitary wasp, were studied on the neuromuscular synapses in lobster walking leg and the rat trigeminal ganglion (TG) neurons. Paired intracellular recordings from the presynaptic axon terminals and the innervating lobster leg muscles revealed that α‐PMTX induced long bursts of action potentials in the presynaptic axon, which resulted in facilitated excitatory and inhibitory synaptic transmission. The action of α‐PMTX was distinct from that of other known facilitatory presynaptic toxins, including sea anemone toxins and α‐scorpion toxins, which modify the fast inactivation of Na+ current. We further characterized the action of α‐PMTX on Na+ channels by whole‐cell recordings from rat trigeminal neurons. We found that α‐PMTX slowed the Na+ channels inactivation process without changing the peak current–voltage relationship or the activation time course of tetrodotoxin (TTX)‐sensitive Na+ currents, and that α‐PMTX had voltage‐dependent effects on the rate of recovery from Na+ current inactivation and deactivating tail currents. The results suggest that α‐PMTX slows or blocks conformational changes required for fast inactivation of the Na+ channels on the extracellular surface. The simple structure of α‐PMTX, consisting of 13 amino acids, would be advantageous for understanding the functional architecture of Na+ channel protein.
Glycine triggers an intracellular calcium influx in oligodendrocyte progenitor cells which is mediated by the activation of both the ionotropic glycine receptor and Na+‐dependent transporters
Authors: Belachew Shibeshih , Malgrange Brigitte , Rigo Jean‐Michel , Rogister Bernard , Leprince Pierre , Hans Gregory , Nguyen Laurent , Moonen Gustave 
Published: March 2003

AbstractUsing fluo‐3 calcium imaging, we demonstrate that glycine induces an increase in intracellular calcium concentration ([Ca2+]i) in cortical oligodendrocyte progenitor (OP) cells. This effect results from a calcium entry through voltage‐gated calcium channels (VGCC), as it is observed only in OP cells expressing such channels, and it is abolished either by removal of calcium from the extracellular medium or by application of anl‐type VGCC blocker. Glycine‐triggered Ca2+influx in OP cells actually results from an initial depolarization that is the consequence of the activation of both the ionotropic glycine receptor (GlyR) and Na+‐dependent transporters, most probably the glycine transporters 1 (GLYT1) and/or 2 (GLYT2) which are colocalized in these cells. Through this GlyR‐ and transporter‐mediated effect on OP intrcellular calcium concentration [Ca2+]i, glycine released by neurons may, as well as other neurotransmitters, serve as a signal between neurons and OP during development.
Protein kinase C activity modulates dendritic differentiation of rat Purkinje cells in cerebellar slice cultures
Authors: Metzger Friedrich , Kapfhammer Josef P. 
Published: March 2003

AbstractThe molecular mechanisms underlying dendritic differentiation in neurons are currently poorly understood. We used slice cultures from rat cerebellum of postnatal day 8 to investigate the effect of protein kinase C (PKC) activity on dendritic development of Purkinje cells. After 12 days in culture under control conditions, Purkinje cells had developed a typical dendritic tree consisting of a few long primary dendrites with shorter side branches. Following treatment with the PKC agonist, phorbol‐12‐myristate‐13‐acetate (PMA), the dendritic tree area was strongly reduced to 32% of control and primary dendrites were short with only a few side branches. Delayed addition of PMA after 6 days resulted in a retraction of existing dendrites, whereas discontinuation of PMA treatment after 6 days resulted in a recovery of the dendritic tree to almost control values. In the presence of the PKC inhibitor, 2‐[1‐(3‐dimethylaminopropyl)indol‐3‐yl]‐3‐(indol‐3‐yl)maleimide (GF109203X), the dendritic tree area was increased to 158% of control with much more ramified branches after 12 days. The overall morphology of the cultures and the survival of Purkinje cells were unaffected by PKC modulators. Our data show that increased activity of PKC inhibits, and reduced activity of PKC promotes dendritic growth. This suggests that PKC activity is a critical regulator of dendritic growth and differentiation in cerebellar Purkinje cells.
Spatio‐temporal characterizations of non‐linear changes in intracranial activities prior to human temporal lobe seizures
Authors: Le Van Quyen M. , Adam C. , Martinerie J. , Baulac M. , Clémenceau S. , Varela F. 
Published: March 2003

AbstractRecent studies have shown that non‐linear analysis of intracranial activities can detect a ‘pre‐ictal phase’ preceding the epileptic seizure. Nevertheless, the dynamical nature of the underlying neuronal process and the spatial extension of this pre‐ictal phase still remain unknown. In this paper, we address these aspects using a new non‐linear measure of dynamic similarity between different parts of intracranial recordings of nine patients with medial temporal lobe epilepsy recorded during transitions to seizure. Our results confirm that non‐linear changes in neuronal dynamics allow, in most cases (16 out of 17), a seizure anticipation several minutes in advance. Furthermore, we show that the spatial distribution of pre‐ictal changes often involves an extended network projecting beyond the limits of the epileptogenic region. Finally, the pre‐ictal phase could frequently (13 out of 17) be characterized with a marked shift toward slower frequencies in upper delta or theta frequency range.
Involvement of the direct striatonigral pathway in levodopa‐induced sensitization in 6‐hydroxydopamine‐lesioned rats
Authors: Bordet Régis , Ridray Sophie , Schwartz Jean‐Charles , Sokoloff Pierre 
Published: March 2003

AbstractInduction of dopamine D3receptor gene expression in 6‐hydroxydopamine‐lesioned rats by repeated administration of levodopa had been suggested to be responsible for behavioural sensitization developing in these animals. Using double in situ hybridization techniques, we show that D3receptor mRNA induction after repeated administration of levodopa took place mainly in dynorphin/substance P‐expressing neurons of the direct striatonigral pathway. In agreement, induction of D3receptor binding sites was evidenced, using 7‐[3H]hydroxy‐N,N‐di‐propyl‐2‐aminotetralin ([3H]7‐OH‐DPAT), in substantia nigra pars reticulata, the projection area of the direct nigrostriatonigral pathway. Changes in D3receptor binding and behavioural sensitization during intermittent administration of levodopa paralleled changes in prodynorphin/preprotachykinin rather than preproenkephalin/prodynorphin and preproenkephalin/preprotachykinin mRNA ratios. Behavioural sensitization, induction of D3receptor binding and changes in prodynorphin/preprotachykinin ratio were all prevented together when levodopa was continuously delivered or intermittently delivered in combination withr‐(+)‐7‐chloro‐8‐hydroxy‐3‐methyl‐1‐phenyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine (SCH 23390), a selective D1receptor antagonist. Our results indicate that functional changes of the direct striatal output pathway, possibly through an interaction between D1and D3receptors at the level of terminals in the substantia nigra pars reticulata, are important for the development of behavioural sensitization.