bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presynaptic kynurenate‐sensitive receptors inhibit glutamate release
Authors: Carpenedo R. , Pittaluga A. , Cozzi A. , Attucci S. , Galli A. , Raiteri M. , Moroni F. 
Published: March 2003

AbstractKynurenic acid is a tryptophan metabolite provided with antagonist activity on ionotropic glutamate and α7 nicotinic acetylcholine receptors. We noticed that in rats with a dialysis probe placed in the head of their caudate nuclei, local administration of kynurenic acid (30–100 nm) significantly reduced glutamate output. Qualitatively and quantitatively similar effects were observed after systemic administration of kynurenine hydroxylase inhibitors, a procedure able to increase brain kynurenate concentrations. Interestingly, in microdialysis studies, methyllycaconitine (0.3–10 nm), a selective α7 nicotinic receptor antagonist, also reduced glutamate output. In isolated superfused striatal synaptosomes, kynurenic acid (100 nm), but not methyllycaconitine, inhibited the depolarization (KCl 12.5 mm)‐induced release of transmitter or previously taken‐up [3H]‐D‐aspartate. This inhibition was not modified by glycine, N‐methyl‐d‐aspartate or subtype‐selective kainate receptor agents, while CNQX or DNQX (10 µm), two AMPA and kainate receptor antagonists, reduced kynurenic acid effects. Low concentrations of kynurenic acid, however, did not modify [3H]‐kainate (high and low affinity) or [3H]‐AMPA binding to rat brain membranes. Finally, because metabotropic glutamate (mGlu) receptors modulate transmitter release in striatal preparations, we evaluated, with negative results, kynurenic acid (1–100 nm) effects in cells transfected with mGlu1, mGlu2, mGlu4 or mGlu5 receptors. In conclusion, our data show that kynurenate‐induced inhibition of glutamate release is not mediated by glutamate receptors. Nicotinic acetylcholine receptors, however, may contribute to the inhibitory effects of kynurenate found in microdialysis studies, but not in those found in isolated synaptosomes.
Distribution of mossy fibre rosettes in the cerebellum of cat and mice: evidence for a parasagittal organization at the single fibre level
Authors: Sultan Fahad 
Published: March 2003

AbstractMossy fibres are the main afferent input to the granular layer of the cerebellar cortex. In this study, the spatial distribution of the mossy fibres' presynaptic enlargements – the so‐called rosettes – were analysed on the single fibre level. Data obtained from the cerebella of cat and mice were compared to look for species differences, and the cerebella of the adult and young mice were also compared to look for developmental changes. The results show that there is a spatial anisotropy in all mossy fibres studied, with neighbouring rosettes being about three times further away from each other along the parasagittal axis and closer to each other in the mediolateral direction. Furthermore, these results suggest that this anisotropy is established at an early developmental stage. The anisotropic orientation of mossy fibres at the single fibre level supports the hypothesis of a timing mechanism in cerebellar function.
Potentiation of 3‐hydroxyglutarate neurotoxicity following induction of astrocytic iNOS in neonatal rat hippocampal cultures
Authors: Kölker Stefan , Ahlemeyer Barbara , Hühne Ricarda , Mayatepek Ertan , Krieglstein Josef , Hoffmann Georg F. 
Published: March 2003

AbstractNeuronal damage in glutaryl‐CoA dehydrogenase deficiency (GDD) has previously been addressed to N‐methyl‐d‐aspartate (NMDA) receptor‐mediated neurotoxicity of the accumulating neurotoxic metabolite 3‐hydroxyglutarate. However, acute encephalopathic crises in GDD patients are typically precipitated by febrile illness or even routine vaccinations, suggesting a potentiating role of inflammatory cytokines. In the present study we investigated the effect of interleukin‐1β and interferon‐γ on 3‐hydroxyglutarate toxicity in rat cortical astrocyte cultures and neonatal rat hippocampal cultures. A cotreatment of both culture systems with interleukin‐1β and interferon‐γ induced the protein expression of astrocytic inducible nitric oxide synthase (iNOS), resulting in increased nitric oxide (NO) production. Cytokine pretreatment alone had no effect on cell viability but potentiated 3‐hydroxyglutarate neurotoxicity. NOS inhibition by aminoguanidine and L‐NAME prevented an iNOS‐mediated potentiation of 3‐hydroxyglutarate neurotoxicity but failed to protect neurons against 3‐hydroxyglutarate alone. In contrast, superoxide dismutase/catalase as well as MK‐801 prevented toxicity of 3‐hydroxyglutarate alone as well as its potentiation by iNOS, supporting a central role of NMDA receptor stimulation with subsequently increased superoxide anion production. It is concluded that the potentiation of 3‐hydroxyglutarate neurotoxicity is most probably due to an induction of astrocytic iNOS and concomitantly increased NO production, enabling enhanced peroxynitrite formation. Thus, we provide evidence for a neuroimmunological approach to the precipitation of acute encephalopathic crises in GDD by inflammatory cytokines.
GFRalpha3 is expressed predominantly in nociceptive sensory neurons
Authors: Orozco Olivia E. , Walus Lee , Sah Dinah W. Y. , Pepinsky R. Blake , Sanicola Michele 
Published: March 2003

AbstractActivation of the RET receptor tyrosine kinase by glial‐derived neurotrophic factor family members is dependent on a family of coreceptors, GFRα1–4. GFRα3 preferentially binds the newest member of the glial‐derived neurotrophic factor family of ligands, artemin. The major site of GFRα3 expression is in the dorsal root ganglion; however, the class of sensory neurons that expresses GFRα3 has not been reported previously. Using immunohistochemical methods, we show that the majority of dorsal root ganglion cells that express GFRα3 also express vanilloid receptor type 1, peripherin, RET, trkA and calcitonin gene‐related peptide. In addition, a significant subpopulation of GFRα3‐expressing cells also binds the lectin IB4. We demonstrate that GFRα3 artemin neurons are immunopositive for markers expected of nociceptors and include a subset of neurons distinct from the GDNF‐responsive population. Our results indicate artemin may exert selective effects on pain sensation.
Oligodendroglial tau filament formation in transgenic mice expressing G272V tau
Authors: Götz Jürgen , Tolnay Markus , Barmettler Robi , Chen Feng , Probst Alphonse , Nitsch Roger M. 
Published: March 2003

AbstractGenetic evidence indicates that several mutations in tau, including G272V, are linked to frontotemporal dementia with parkinsonism. We expressed this mutation in mouse brains by combining a prion protein promoter‐driven expression system with an autoregulatory transactivator loop that resulted in high expression of human G272V tau in neurons and in oligodendrocytes. We show that G272V tau can form filaments in murine oligodendrocytes. Electron microscopy established that the filaments were either straight or had a twisted structure; these were 17–20 nm wide and had a periodicity of ≈ 75 nm. Filament formation was associated with tau phosphorylation at distinct sites, including the AT8 epitope 202/205 in vivo. Immunogold electron microscopy of sarcosyl‐extracted spinal cords from G272V transgenic mice using phosphorylation‐dependent antibodies AT8 or AT100 identified several sparsely gold‐labelled 6‐nm filaments. In the spinal cord, fibrillary inclusions were also identified by thioflavin‐S fluorescent microscopy in oligodendrocytes and motor neurons. These results establish that expression of the G272V mutation in mice causes oligodendroglial fibrillary lesions that are similar to those seen in human tauopathies.
Calcium‐activated potassium current clamps the dark potential of vertebrate rods
Authors: Moriondo Andrea , Pelucchi Bruna , Rispoli Giorgio 
Published: March 2003

AbstractVertebrate photoreceptors respond to light with a graded hyperpolarization from a membrane potential in the dark of ≈ −35 mV. The present work investigates the physiological role of the Ca2+‐activated K+ current in the photovoltage generation in mechanically isolated rods from salamander retina. Membrane current or voltage in isolated rods was recorded from light‐ and dark‐adapted rods under voltage‐ or current‐clamp conditions, respectively. In light‐adapted rods of the salamander, selective blockade of Ca2+‐activated K+ channels by means of charybdotoxin depolarized the plasma membrane of current‐clamped rods by ≈ 30 mV, from a resting potential of ≈ −35 mV. A similar depolarization was observed if external Ca2+ (1 mm) was substituted with Ba2+ or Sr2+. Under control conditions, the injection of currents of increasing amplitude (up to −100 pA, to mimic the current entering the rod outer segment) could not depolarize the membrane potential beyond a saturating value of ≈ −20 mV. However, in the presence of charybdotoxin, rods depolarized up to +20 mV. In experiments with dark‐adapted current‐clamped rods, charybdotoxin perfusion lead to transient depolarizations up to 0 mV and steady‐state depolarizations of ≈ 5 mV above the dark resting potential. Finally, the recovery phase of the voltage response to a flash of light in the presence of charybdotoxin showed a transient overshoot of the membrane potential. It was concluded that Ca2+‐activated K+ current is necessary for clamping the rod photovoltage to values close to the dark potential, thus allowing faithful single photon detection and correct synaptic transmission.
Effects of selective thalamic and prelimbic cortex lesions on two types of visual discrimination and reversal learning
Authors: Chudasama Yogita , Bussey Timothy J. , Muir Janice L. 
Published: March 2003

AbstractThe effects of excitotoxic lesions of the mediodorsal nucleus of the thalamus, the anterior thalamic nuclei and of the prelimbic cortex were examined on two tests of discrimination and reversal learning. In experiment 1A (visual discrimination and reversal), rats were required to discriminate two stimuli, and respond to the stimulus associated with reward (the S+ stimulus). There was no effect of lesion on acquisition of this task. However, when stimulus–reward contingencies were reversed, animals with lesions of the mediodorsal nucleus of the thalamus made significantly more errors than control animals or animals of other lesion groups. In experiment 1B (conditional discrimination), animals were required to learn a rule of the type ‘If stimulus A then go left, if stimulus B then go right’. No main effect of lesion on acquisition was observed in this experiment. To test the generality of the reversal effect obtained in experiment 1A, a second cohort of animals with the same lesions was tested on acquisition of the visuospatial conditional task immediately postsurgery, followed by the reversal of the conditional rule (experiment 2). As in experiment 1B, no main effect of lesion group was observed during acquisition of the task. However, lesions of the mediodorsal nucleus of the thalamus resulted in a mild impairment according to number of sessions required to attain criterion performance of the task when the response rule was reversed. The results of the present study provide evidence for a role for the mediodorsal nucleus of the thalamus in new learning, particularly when stimulus–reward contingencies are reversed. Furthermore, they show that the functions of this thalamic nucleus can be dissociated from those of the anterior thalamus and the prelimbic cortex.
Antisense oligodeoxynucleotide‐induced suppression of basal forebrain NMDA‐NR1 subunits selectively impairs visual attentional performance in rats
Authors: Turchi Janita , Sarter Martin 
Published: March 2003

AbstractIt is generally agreed that basal forebrain neuronal circuits contribute to the mediation of the ability to detect, select and discriminate signals, to suppress the processing of irrelevant information, and to allocate processing resources to competing tasks. Rats were trained in a task designed to assess sustained attention, or in a cued discrimination task that did not tax attentional processes. Animals were equipped with guide cannula to infuse bilaterally antisense oligodeoxynucleotides (ODNs) against the N‐methyl‐d‐aspartate (NMDA) NR1 subunits, or missense ODNs, into the substantia innominata of the basal forebrain. Infusions of antisense or missense ODNs did not affect cued visual discrimination performance. Infusions of antisense ODNs dose‐dependently impaired sustained attention performance by selectively decreasing the animals' ability to detect signals while their ability to reject nonsignal trials remained unchanged. The detrimental attentional effects of antisense infusions were maximal 24 h after the third and final infusion, and performance returned to baseline 24 h later. Missense infusions did not affect attentional performance. Separate experiments demonstrated extensive suppression of NR1 subunit immunoreactivity in the substantia innominata. Furthermore, infusions of antisense did not produce neurotoxic effects in that region as demonstrated by the Fluoro‐Jade method. The present data support the hypothesis that NMDA receptor (NMDAR) stimulation in the basal forebrain, largely via glutamatergic inputs originating in the prefrontal cortex, represents a necessary mechanism to activate the basal forebrain corticopetal system for mediation of attentional performance.
N‐methyl‐d‐aspartate receptor‐mediated increase of neurogenesis in adult rat dentate gyrus following stroke
Authors: Arvidsson Andreas , Kokaia Zaal , Lindvall Olle 
Published: March 2003

AbstractNeurogenesis in the adult rat dentate gyrus was studied following focal ischemic insults produced by middle cerebral artery occlusion (MCAO). Animals were subjected to either 30 min of MCAO, which causes damage confined to the striatum, or 2 h of MCAO, which leads to both striatal and cortical infarction. When compared to sham‐operated rats, MCAO‐rats showed a marked increase of the number of cells double‐labelled for 5‐bromo‐2′‐deoxyuridine‐5′‐monophosphate (BrdU; injected during 4–6 days postischemia) and neuronal‐specific antigen (NeuN; a marker of postmitotic neurons) in the ipsilateral dentate granule cell layer and subgranular zone at 5 weeks following the 2 h insult. Only a modest and variable increase of BrdU‐labelled cells was found after 30 min of MCAO. The enhanced neurogenesis was not dependent on cell death in the hippocampus, and its magnitude was not correlated to the degree of cortical damage. Systemic administration of the N‐methyl‐d‐aspartate (NMDA) receptor blocker dizocilpine maleate (MK‐801) completely suppressed the elevated neurogenesis following 2 h of MCAO. Our findings indicate that stroke leads to increased neurogenesis in the adult rat dentate gyrus through glutamatergic mechanisms acting on NMDA receptors. This modulatory effect may be mediated through changes in the levels of several growth factors, which occur after stroke, and could influence various regulatory steps of neurogenesis.
Effects of cannabinoids on prefrontal neuronal responses to ventral tegmental area stimulation
Authors: Pistis Marco , Porcu Giuseppe , Melis Miriam , Diana Marco , Luigi Gessa Gian 
Published: March 2003

AbstractCannabinoids activate the firing of mesoprefrontocortical dopamine neurons and release dopamine in the prefrontal cortex. This study was undertaken with the aim of clarifying the interaction between cannabinoids and mesocortical system in the prefrontal cortex. The effect of Δ9‐tetrahydrocannabinol (Δ9‐THC) and the synthetic CB1 agonist WIN55,212–2 (WIN) was studied by extracellular single unit recordings, in chloral hydrate anaesthetised rats, on the spontaneous activity of pyramidal neurons and on the inhibition produced on these neurons by the electrical stimulation of the ventral tegmental area (VTA). Intravenously administered Δ9‐THC and WIN (1.0 and 0.5 mg/kg, respectively), increased the firing rate of pyramidal neurons projecting to the VTA. VTA stimulation produced a phasic inhibition (167 ± 6 ms) in 79% of prefrontal cortex pyramidal neurons. Δ9‐THC and WIN reverted this inhibition in 73% and 100% of the neurons tested, respectively. The subsequent administration of the selective CB1 antagonist SR141716A (1 mg/kg) readily suppressed the effects of both cannabinoids and restored the inhibitory response to VTA stimulation. Moreover, when administered alone, SR141716A prolonged the inhibition in 55.6% of the neurons tested. The results indicate that stimulation of CB1 receptors by cannabinoids results in an enhanced excitability of prefrontal cortex pyramidal neurons as indexed by the suppression of the inhibitory effect of VTA stimulation and by the increase in firing rate of antidromically identified neurons projecting to the VTA. Furthermore, our results support the view that endogenous cannabinoids exert a negative control on dopamine activity in the prefrontal cortex. This study may be relevant in helping to understand the influence of cannabinoids on cognitive processes mediated by the prefrontal cortex.
Chronic levodopa therapy does not improve skilled reach accuracy or reach range on a pasta matrix reaching task in 6‐OHDA dopamine‐depleted (hemi‐Parkinson analogue) rats
Authors: Metz Gerlinde A. S. , Farr Tracy , Ballermann Mark , Whishaw Ian Q. 
Published: March 2003

Abstractl‐dopa therapy reverses some but not all of the motor deficits in human Parkinson patients. Although a number rat analogues of human Parkinson's disease have been developed for evaluating the efficacy of drug therapies, it is not known whether l‐dopa has a similar selective action on the motor symptoms in the rat models. To examine the effectiveness of l‐dopa in reversing the motor deficits in rats, we administered 6‐OHDA unilaterally to produce hemi‐Parkinson rats, which were then trained to reach for food using either their impaired (contralateral to the lesion) limb or their good (ipsilateral to the lesion) limb. To assess the skill, accuracy and range of limb movement, rats reached for pasta from a horizontal array of 260 vertically orientated pieces of pasta. The number and location of pasta pieces taken from this matrix was calculated and the qualitative aspects of the reaching movements were rated. The quantitative data on pasta sticks retrieved indicated that forelimb extension and movement radius around the shoulder joint was reduced by 6‐OHDA treatment and did not improve after chronic l‐dopa treatment. The qualitative analysis showed that grasping patterns, paw movements and body movements impaired by the lesion were also not improved by l‐dopa treatment. These findings are the first in the rat to suggest that whereas l‐dopa has a general activating effect on the rat's whole‐body movements, as displayed in contralateral rotation, its effectiveness does not extend to skilled forelimb movements. The results are discussed in relationship to the idea that the restoration of some skilled movements may require normal synaptic function.
D2‐like dopamine receptor activation excites rat dorsal raphe 5‐HT neurons in vitro
Authors: Haj‐Dahmane Samir 
Published: March 2003

AbstractThe aim of the present study was to investigate the effect of dopamine (DA) on the excitability of dorsal raphe nucleus (DRN) 5‐hydroxytryptamine (5‐HT) neurons using the patch‐clamp technique in brain slices. Bath application of DA (1–300 µm) produced a concentration‐dependent membrane depolarization in all 5‐HT neurons examined. This effect persisted in the presence of tetrodotoxin (TTX; 1 µm) and low extracellular calcium. Moreover, blockade of ionotropic glutamate receptors with 6,7‐dinitroquinoxaline‐2,3‐dione (DNQX) and 2‐amino‐5‐phosphonopentanoic acid (AP5) did not prevent DA‐induced depolarization, indicating that it was mediated by a direct effect of DA on 5‐HT neurons. The DA‐induced depolarization was not antagonized by selective α1‐adrenergic receptor antagonists, prazosin and WB 4101, but by a nonselective DA receptor antagonist, haloperidol. In addition, the selective D2‐like receptor agonist quinpirole and antagonist sulpiride mimicked and blocked DA‐induced depolarization, respectively. These results indicate that DA‐induced membrane depolarization in DRN 5‐HT neurons is mediated by the activation of D2‐like DA receptors. The DA‐induced membrane depolarization and inward current were associated with an increase in membrane conductance. Examination of the current–voltage (I–V) relationship for the DA‐induced inward current revealed that the amplitude of the current increased with membrane hyperpolarization and reversed polarity at a potential near −15 mV. These data suggest that DA‐induced depolarization in DRN 5‐HT neurons is not mediated by a decrease in potassium conductance, but most likely by the activation of a nonselective cation current.
Inhibition of synaptically evoked cortical acetylcholine release by intracortical glutamate: involvement of GABAergic neurons
Authors: Materi Leticia M. , Semba Kazue 
Published: March 2003

AbstractCortical acetylcholine (ACh) has been shown to regulate diverse cognitive processes and its release can be regulated by neuromodulators that act presynaptically at cholinergic terminals. The neocortex receives dense glutamatergic input from thalamocortical and other fibres. The present study usedin vivomicrodialysis to examine, and pharmacologically characterize, the effect of glutamate on cortical ACh release evoked by electrical stimulation of the pedunculopontine tegmental nucleus in urethane‐anaesthetized rats. All drugs were administered locally within the cortex by reverse dialysis. Application of glutamate had no detectable effect on spontaneous ACh release but reduced evoked cortical ACh efflux in a concentration‐dependent manner. This effect was mimicked by the glutamate transporter blockerl‐trans‐pyrrolidine‐2,4‐dicarboxylic acid, as well as by the ionotropic glutamate receptor agonists N‐methyl‐d‐aspartic acid and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid, and was blocked by the ionotropic glutamate receptor antagonists 6,7‐dinitroquinoxaline‐2,3‐dione and (+/–)‐3‐(2‐carboxypiperazin‐4yl)‐propyl‐1‐phosphonic acid. Glutamate application also increased extracellular adenosine levels but the simultaneous delivery of the broad‐spectrum adenosine receptor antagonist caffeine failed to affect the inhibitory action of glutamate on evoked ACh release. However, the effect of glutamate was fully blocked by simultaneous delivery of the GABAAreceptor antagonist bicuculline and partially blocked by the GABABreceptor antagonist phaclofen. These results suggest that ionotropic glutamate receptor activation by glutamate inhibits evoked cortical ACh release via an indirect pathway involving GABAergic neurons in the cortex.