bluuebunny/crossref_metadata_2025_split huggingface dataset:
NMDA antagonists exacerbate neuronal death caused by proteasome inhibition in cultured cortical and striatal neurons
Authors: Snider B. Joy , Tee Lee Y. , Canzoniero Lorella M. T. , Babcock Debra J. , Choi Dennis W. 
Published: March 2003

AbstractThe proteasome is involved in multiple cellular processes including control of the cell cycle, apoptosis and intracellular signalling; loss of proteasome function has been postulated to participate in the pathogenesis of triplet repeat diseases. We examined the vulnerability of central neurons to proteasome inhibition and tested the ability of anti‐excitotoxic and anti‐apoptotic treatments to attenuate proteasome inhibition‐induced neuronal death. Exposure of murine neocortical cultures to proteasome inhibitors (0.1–10 µmclasto‐lactacystin β‐lactone or MG‐132) for 48 h resulted in widespread neuronal death associated with a reduction in intracellular free calcium; higher inhibitor concentrations killed astrocytes. Cultured striatal neurons were more vulnerable than cortical neurons. Within each population, the NADPH diaphorase‐positive neuronal subpopulation was more vulnerable than the general neuronal population. Enhancing calcium entry with S(–)BayK8644 or kainate, or blocking apoptosis with cycloheximide, actinomycin D or Z‐VAD.FMK attenuated neuronal death, whereas, reducing calcium entry with NMDA antagonists or R(+)BayK8644 potentiated neuronal death. These findings suggest that proteasome inhibition can induce selective neuronal apoptosis associated with intracellular calcium starvation, and point to manipulation of intracellular calcium as a specific therapeutic strategy. In particular, concern is raised that glutamate receptor antagonists might exacerbate, rather than attenuate, proteasome inhibition‐induced neuronal death.
Brain macrophages inhibit gap junctional communication and downregulate connexin 43 expression in cultured astrocytes
Authors: Rouach N. , Calvo C.‐F. , Glowinski J. , Giaume C. 
Published: March 2003

AbstractAstrocytes are typically interconnected by gap junction channels that allow, in vitro as well as in vivo, a high degree of intercellular communication between these glial cells. Using cocultures of astrocytes and neurons, we have demonstrated that gap junctional communication (GJC) and connexin 43 (Cx43) expression, the major junctional protein in astrocytes, are controlled by neuronal activity. Moreover, neuronal death downregulates these two parameters. Because in several brain pathologies neuronal loss is associated with an increase in brain macrophage (BM) density, we have now investigated whether coculture with BM affects astrocyte gap junctions. We report here that addition of BM for 24 h decreases the expression of GJC and Cx43 in astrocytes in a density‐dependent manner. In contrast, Cx43 is not detected in BM and no heterotypic coupling is observed between the two cell types. A soluble factor does not seem to be involved in these inhibitions because they are not observed either in the presence of BM conditioned media or in the absence of direct contact between the two cell types by using inserts. These observations could have pathophysiological relevance as neuronal death, microglial proliferation and astrocytic reactions occur in brain injuries and pathologies. Because astrocyte interactions with BM and dying neurons both result in the downregulation of Cx43 expression and in the inhibition of GJC, a critical consequence on astrocytic phenotype in those situations could be the inhibition of gap junctions.
Forced swimming triggers vasopressin release within the amygdala to modulate stress‐coping strategies in rats
Authors: Ebner Karl , Wotjak Carsten T. , Landgraf Rainer , Engelmann Mario 
Published: March 2003

AbstractPreviously, we have demonstrated that forced swimming triggers the release of arginine vasopressin (AVP) within the septum of rats, where AVP modulates stress‐coping strategies. The present study was designed to examine the effects of forced swimming on the release of AVP within the amygdala. Therefore, adult male Wistar rats were chronically implanted with a microdialysis probe aimed at the amygdala to monitor the local release of AVP under both resting and stress conditions. A 10‐min forced swimming session caused a significant increase in the extracellular AVP concentration (to 366 ± 90% of baseline; P < 0.05) within this brain area. In a subsequent experiment we investigated the physiological impact of the stressor‐induced release of AVP by administrating the AVP V1 receptor antagonist d(CH2)5Tyr(Me)AVP into the amygdala via inverse microdialysis. Bilateral antagonist treatment modulated the behavioural response acutely by increasing the time the animals spent struggling and by reducing the time the animals floated. Our results demonstrate a significant activation of the vasopressinergic system within the amygdala in response to forced swimming. AVP released within the amygdala seems to be involved in the generation of passive coping strategies in stressful situations. Taken together with previous findings the results of the present study suggest that AVP is released within septum and amygdala to balance the behavioural response during forced swimming.
The human startle reflex and pons activation: a regional cerebral blood flow study
Authors: Pissiota Anna , Frans Örjan , Fredrikson Mats , Långström Bengt , Flaten Magne Arve 
Published: March 2003

AbstractUsing positron emission tomographic measurements of regional cerebral blood flow, we report activation of a medial pons area in humans during acoustic startle stimulation. Eight healthy volunteers were scanned during rest and when presented startle‐eliciting stimuli. We performed a theory‐driven directed search for activity in the nucleus reticularis pontis caudalis, situated in the pons. Because habituation of cerebellar activity during acoustic startle repetition has been reported [Timmann, D., Musso, C., Kolb, F.P., Rijntjes, M., Juptner, M., Muller, S.P., Diener, H.C. & Weiller, C. (1998) J. Neurol. Neurosurg. Psychiatry65, 771–773], we also predicted habituation in the cerebellum and in the pons as a function of startle repetition. Measurements of eye electromyography validated the presence of a startle response and its habituation. Analysis of regional cerebral blood flow revealed higher neural activity during startle stimulation than at rest in a medial pons area consistent with the location of the pontine reticular nucleus. As a consequence of startle repetition, regional cerebral blood flow increased in the medial cerebellum, and habituated in the ventral cerebellum and in a ventral pons area separate from the pontine reticular nucleus. In the ventral pons, but not in the pontine reticular nucleus, regional cerebral blood flow and the startle reflex were positively correlated. In the cerebellum both positive and negative correlations with the startle reflex were observed. Thus we conclude that the neurofunctional correlates of the startle circuit and its habituation in humans are similar to that previously described in animals.
A single olfactory receptor specifically binds a set of odorant molecules
Authors: Gaillard Isabelle , Rouquier Sylvie , Pin Jean‐Philippe , Mollard Patrice , Richard Sylvain , Barnabé Cécile , Demaille Jacques , Giorgi Dominique 
Published: March 2003

AbstractThe sense of smell is mediated by the initiation of action potential in olfactory sensory neurons during odor stimulation. However, little is known about odorant‐olfactory receptor (OR) recognition mechanisms. In the present work, we identified the structural motifs of odorant molecules required to activate mouse OR912‐93 by detection of the odorant response using calcium measurement in cells transfected with OR and Gαq and Gα15 proteins. The use of sets of odorants led to the identification of ketones with an aliphatic carbon chain length ≥ four carbon atoms and a carbonyl group preferentially located in position C2 or C3. The threshold of detection of these odorants is as low as 10−6−10−8m. No other odorant ligand, out of 70 representatives of the odorant world, was active. The human ortholog of OR912‐93 is not functional, suggesting that apart from a stop‐mutation located at the 5′‐end that was corrected in the construct, it incurred other deleterious mutations during evolution.
Differential subcellular localization of the 5‐HT3‐As receptor subunit in the rat central nervous system
Authors: Miquel M.‐C. , Emerit M. B. , Nosjean A. , Simon A. , Rumajogee P. , Brisorgueil M.‐J. , Doucet E. , Hamon M. , Vergé D. 
Published: March 2003

AbstractFollowing the cloning and sequencing of the A subunit of the 5‐HT3 receptor, two alternatively spliced isoforms, 5‐HT3‐AS and 5‐HT3‐AL, have been identified. In order to analyse the distribution of the receptor, a polyclonal antibody has been produced against the short form which is the most abundant in the central nervous system [Doucet et al. (2000) Neuroscience 95, 881–892]. As expected from the recognition of functional 5‐HT3 receptors, immunostaining by this anti‐5‐HT3‐R‐AS antibody matched the distribution of the high‐affinity 5‐HT3 binding sites in the rat brain and spinal cord. 5‐HT3‐AS‐like immunoreactivity was detected at low levels in the limbic system, particularly in the amygdala and the hippocampus, and in the frontal, piriform and entorhinal cortices. High levels of immunoreactivity were found in the brainstem, mainly in the nucleus tractus solitarius and the nucleus of the spinal tract of the trigeminal nerve, and in the dorsal horn of the spinal cord. At the ultrastructural level, immunostaining was generally found associated with axons and nerve terminals (70–80%) except in the hippocampus, where labelled dendrites were more abundant (56%). This preferential localization on nerve endings is consistent with the well‐documented physiological role of 5‐HT3 receptors in the control of neurotransmitter release. However, the different distribution in the hippocampus raises the question of whether differential addressing mechanisms exist for preferentially targeting 5‐HT3 receptors to postsynaptic dendritic sites as compared to presynaptic nerve endings, depending on the nature of the neurons bearing these receptors.
Speech listening specifically modulates the excitability of tongue muscles: a TMS study
Authors: Fadiga Luciano , Craighero Laila , Buccino Giovanni , Rizzolatti Giacomo 
Published: March 2003

AbstractThe precise neural mechanisms underlying speech perception are still to a large extent unknown. The most accepted view is that speech perception depends on auditory‐cognitive mechanisms specifically devoted to the analysis of speech sounds. An alternative view is that, crucial for speech perception, it is the activation of the articulatory (motor) gestures that generate these sounds. The listener understands the speaker when his/her articulatory gestures are activated (motor theory of speech perception). Here, by using transcranial magnetic stimulation (TMS), we demonstrate that, during speech listening, there is an increase of motor‐evoked potentials recorded from the listeners' tongue muscles when the presented words strongly involve, when pronounced, tongue movements. Although these data do not prove the motor theory of speech perception, they demonstrate for the first time that word listening produces a phoneme specific activation of speech motor centres.
Regulation of acetylcholine release by muscarinic receptors at the mouse neuromuscular junction depends on the activity of acetylcholinesterase
Authors: Minic Jasmina , Molgó Jordi , Karlsson Evert , Krejci Eric 
Published: March 2003

AbstractMuscarinic acetylcholine receptors (mAChRs) play an important role in regulating the release of acetylcholine (ACh) in various tissues. We used subtype‐specific antibodies and a fluorescent‐labelled muscarinic toxin to demonstrate that mammalian neuromuscular junction expresses mAChR subtypes M1 to M4, and that localization of all subtypes is highly restricted to the innervated part of the muscle. To elucidate the roles of the mAChR subtypes regulating ACh release, we measured the mean quantal content of endplate potentials in isolated mouse phrenic–hemidiaphragm preparations in which release was reduced by a low Ca2+/high Mg2+ medium. Muscarine decreased evoked ACh release in normal junctions but, depending on the concentration, reduced or increased transmitter release in collagen Q‐deficient junctions completely lacking acetylcholinesterase (AChE). Both effects were also seen in normal junctions when AChE was inhibited by various doses of fasciculin‐2. Block of mAChRs by atropine had no effect on evoked release at normal junctions, but decreased release at junctions lacking AChE. The muscarine‐elicited depression of ACh release in normal junctions was completely abolished by pertussis toxin or methoctramine pretreatment, but was not affected by muscarinic toxin MT‐3, thus indicating the involvement of the M2 mAChR. The muscarine‐induced increase of ACh release in AChE‐deficient junctions was not affected by pertussis toxin, but was completely blocked by MT‐7, a specific M1 mAChR antagonist. Our results show that the M1 and M2 mAChRs have opposite presynaptic functions in modulating quantal ACh release, and that regulation of release by the two receptor subtypes depends on the functional state of AChE at the neuromuscular junction.
Glucocorticoids interact with the basolateral amygdala β‐adrenoceptor–cAMP/cAMP/PKA system in influencing memory consolidation
Authors: Roozendaal Benno , Quirarte Gina L. , McGaugh James L. 
Published: March 2003

AbstractInfusion of a β‐adrenoceptor antagonist into the basolateral nucleus of the amygdala (BLA) blocks memory enhancement induced by systemic or intra‐BLA administration of a glucocorticoid receptor (GR) agonist. As there is evidence that glucocorticoids interact with the noradrenergic signalling pathway in activating adenosine 3′,5′‐cyclic monophosphate (cAMP), the present experiments examined whether glucocorticoids influence the β‐adrenoceptor–cAMP system in the BLA in modulating memory consolidation. Male, Sprague–Dawley rats received bilateral infusions of atenolol (a β‐adrenoceptor antagonist), prazosin (an α1‐adrenoceptor antagonist) or Rp‐cAMPS (a protein kinase A inhibitor) into the BLA 10 min before inhibitory avoidance training and immediate post‐training intra‐BLA infusions of the GR agonist, RU 28362. Atenolol and Rp‐cAMPS, but not prazosin, blocked 48‐h retention enhancement induced by RU 28362. A second series of experiments investigated whether a GR antagonist alters the effect of noradrenergic activation in the BLA on memory consolidation. Bilateral intra‐BLA infusions of the GR antagonist, RU 38486, administered 10 min before inhibitory avoidance training completely blocked retention enhancement induced by α1‐adrenoceptor activation and attenuated the dose–response effects of post‐training intra‐BLA infusions of clenbuterol (a β‐adrenoceptor agonist). However, the GR antagonist did not alter retention enhancement induced by post‐training intra‐BLA infusions of 8‐Br‐cAMP (a synthetic cAMP analogue). These findings suggest that glucocorticoids influence the efficacy of noradrenergic stimulation in the BLA on memory consolidation via an interaction with the β‐adrenoceptor–cAMP cascade, at a locus between the membrane‐bound β‐adrenoceptor and the intracellular cAMP formation site.
The anabolic androgenic steroid, nandrolone decanoate, increases the density of Fos‐like immunoreactive neurons in limbic regions of guinea‐pig brain
Authors: Johansson‐Steensland Pia , Nyberg Fred , Chahl Loris 
Published: March 2003

AbstractThe increased abuse of anabolic androgenic steroids is a major concern because of physiological and psychological side‐effects. In some individuals they induce dramatic behavioural changes such as increased aggression, anxiety and depression. The mechanisms behind these behavioural changes are still poorly understood. In order to obtain information on the brain regions affected by anabolic androgenic steroids, the distribution of neurons containing c‐Fos, the protein product of the immediate early gene c‐fos, and Fos‐related antigens was studied following chronic treatment of guinea‐pigs with a high dose of nandrolone decanoate (15 mg/kg i.m. daily for 14 days). The behaviour of the guinea‐pigs was monitored for 1 h each day. Animals treated with nandrolone exhibited a significantly greater incidence of biting behaviour during the 14 day treatment period than vehicle‐treated animals. A significantly greater density of c‐Fos and Fos‐related antigen‐positive neurons was found in the central nucleus of the amygdala, and of Fos‐related antigen‐positive neurons in the frontal cortex, the shell of the nucleus accumbens and the supraoptic nucleus in nandrolone‐treated animals than in vehicle controls. Therefore, nandrolone induced Fos in brain regions involved in stress, behavioural responses and reward. The increased Fos expression in these limbic brain regions is of particular interest in relation to the behavioural changes reported in humans who abuse anabolic androgenic steroids and the abuse potential of these drugs.
Nitric oxide‐dependent damage to neuronal mitochondria involves the NMDA receptor
Authors: Stewart V. C. , Heslegrave A. J. , Brown G. C. , Clark J. B. , Heales S. J. R. 
Published: March 2003

AbstractCytokine‐stimulated astrocytes produce nitric oxide, which can inhibit components of the mitochondrial respiratory chain. We have previously demonstrated that prolonged exposure (48 h) to rat astrocytic nitric oxide damages complexes II–III and IV of neighbouring rat neurons in coculture, resulting in neuronal death. Expanding on these observations, we have now shown that the NMDA receptor antagonist, MK‐801, prevents this damage, suggesting involvement of glutamate. We postulate that astrocyte‐derived nitric oxide stimulates release of neuronal glutamate. Indeed we demonstrate that neurons incubated with nitric oxide‐generating astrocytes display enhanced glutamate release. Furthermore, direct exposure to the nitric oxide donor, DETA‐NONOate resulted in a loss of activity of all the neuronal mitochondrial complexes, which was again prevented by MK‐801. Thus, nitric oxide, generated by both cytokine‐stimulated astrocytes and by a nitric oxide donor, causes activation of the NMDA receptor leading to damage to the neuronal mitochondrial respiratory chain. Glutamate exposure is known to damage the neuronal mitochondrial respiratory chain via neuronal nitric oxide synthase. Therefore, we propose that astrocyte‐derived nitric oxide is capable of eliciting neuronal glutamate release, which in turn activates the neuronal NMDA receptor and stimulates further formation of reactive nitrogen species via neuronal nitric oxide synthases, leading to mitochondrial damage and neuronal death. Our findings support the hypothesis that glutamate, reactive nitrogen species and mitochondrial dysfunction may have a role in the neurodegenerative process.
Physiological properties of central amygdala neurons: species differences
Authors: Dumont Éric C. , Martina Marzia , Samson Rachel D. , Drolet Guy , Paré Denis 
Published: March 2003

AbstractThe connections of limbic structures are remarkably constant across species. However, different species express fear in distinct ways. Because the central amygdaloid nucleus is considered an important mediator of fear responses, we compared the physiological properties of central amygdala neurons in guinea pigs, rats and cats using whole‐cell recordings in coronal slicesin vitro. In guinea pigs, most central medial and lateral neurons displayed an outward rectification that delayed firing onset in response to depolarizing current pulses (hence the designation late‐firing neurons). Late‐firing neurons were also prevalent in the lateral sector of the cat central nucleus. In contrast, late‐firing neurons were rare in the rat central nucleus and the cat central medial nucleus. There, most neurons generated Ni2+‐sensitive low‐threshold bursts of Na+spikes and/or displayed pronounced inward rectification in the hyperpolarizing direction. Species differences in passive properties were also observed, but they were mainly related to the relative prevalence of late‐firing cells. Indeed, late‐firing cells had a significantly lower input resistance and more negative membrane potential than other types of central neurons. Thus, there are marked species differences in the physiological properties of central neurons. Because the synaptic responsiveness of neurons is constrained by their physiological properties, our findings raise the possibility that the contrasting behavioural responsiveness observed across species is partly dependent on the species‐specific physiological properties of central neurons.
Ultrastructural evaluation of calcitonin gene‐related peptide immunoreactivity in the human cochlea and vestibular endorgans
Authors: Kong Wie‐Jia , Scholtz Arne W. , Kammen‐Jolly Keren , Glückert Rudolf , Hussl Burkhard , Von Cauvenberg Paul B. , Schrott‐Fischer Anneliese 
Published: March 2003

AbstractCalcitonin gene‐related peptide (CGRP) is a neuropeptide widely distributed in the peripheral and central nervous system. Demonstrated in the efferent systems of the mammalian cochlea and vestibule, immunoreactive patterns of CGRP may vary by species. There is, however, no information in the literature investigating CGRP localization in the human cochlea. In the present study, the ultrastructural localization of CGRP immunoreactivity was evaluated in the human inner ear with immunoelectron microscopy. It was found that, in human cochlea, CGRP immunoreactivity was located in unmyelinated nerve fibres of the spiral lamina, inner spiral fibres beneath inner hair cells, tunnel spiral fibres, tunnel crossing fibres and outer radial fibres. In endorgans of human vestibule, CGRP immunoreactivity was located in vesiculated nerve fibres and bouton‐type nerve terminals which were seen to contact afferent nerve chalices surrounding type I sensory cells and afferent nerve fibres, or to form an en passant contact with afferent dendrites. CGRP immunoreactivity appeared to be confined to efferent systems in all cases. This study presents evidence that CGRP could serve a role in neurotransmission or neuroregulation in both cochlear and vestibular efferent systems of human.
Phosphorylation of GluR4 AMPA‐type glutamate receptor subunit by protein kinase C in cultured retina amacrine neurons
Authors: Carvalho Ana Luísa , Correia Susana , Faro Carlos J. , Duarte Carlos B. , Carvalho Arsélio P. , Pires Euclides M. V. 
Published: March 2003

AbstractWe have previously reported that the activity of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) receptors is potentiated by protein kinase C (PKC) in cultured chick retina amacrine neurons, and that constitutive PKC activity is necessary for basal AMPA receptor activity (Carvalho et al., 1998). In this study, we evaluated the phosphorylation of the GluR4 subunit, which is very abundant in cultured amacrine neurons, to correlate it with the effects of PKC on AMPA receptor activity in these cells. 32P‐labelling of GluR4 increased upon AMPA receptor stimulation or cell treatment with phorbol 12‐myristate 13‐acetate (PMA) before stimulating with kainate. By contrast, phosphorylation of GluR4 was not changed when PKC was inhibited by treating the cells with the selective PKC inhibitor GF 109203X before stimulation with kainate. We conclude that GluR4 is phosphorylated upon PKC activation and/or stimulation of AMPA receptors in cultured amacrine cells. Additionally, AMPA receptor activation with kainate in cultured chick amacrine cells leads to translocation of conventional and novel PKC isoforms to the cell membrane, suggesting that PKC could be activated upon AMPA receptor stimulation in these cells.