bluuebunny/crossref_metadata_2025_split huggingface dataset:
LPS/IFN‐γ cytotoxicity in oligodendroglial cells: role of nitric oxide and protection by the anti‐inflammatory cytokine IL‐10
Authors: Molina‐Holgado Eduardo , Vela José Miguel , Arévalo‐Martín Angel , Guaza Carmen 
Published: March 2003

AbstractProinflammatory mediators have been implicated in demyelinating disorders, including multiple sclerosis, whereas it has been proposed that the anti‐inflammatory cytokines interleukin‐ (IL‐) 4 and IL‐10 participate in disease recovery. The present study analysed the effect of interferon‐γ (IFN‐γ) and bacterial endotoxin (lipopolysaccharide, LPS) on proliferation and survival of progenitors and differentiated oligodendrocytes. We also investigated the presence of receptors for IL‐4 and IL‐10 in oligodendroglial cells and explored a possible protective action of IL‐4 and IL‐10 in cultures following LPS/IFN‐γ. Finally, the role of endogenous nitric oxide (NO) on cell viability and the modulatory action of IL‐4 and IL‐10 on inducible nitric oxide synthase (iNOS) expression were also analysed. We report that LPS and/or IFN‐γ reduced proliferation and viability of oligodendroglial cells. Cell death, presumably by apoptosis as evidence by TUNEL and Annexin V binding, was observed following LPS/IFN‐γ, progenitors being more sensitive than differentiated cells. At both developmental stages, LPS/IFN‐γ‐treated cultures expressed iNOS protein and released micromolar concentrations of NO. In progenitors, LPS/IFN‐γ‐mediated cell damage was partially dependent on endogenous NO production, whereas NO was fundamental for cytotoxicity of differentiated oligodendrocytes. Both cell types expressed mRNA for IL‐4 and IL‐10 receptors and expression of IL‐10 receptors at the protein level was also demonstrated. Treatment with either cytokine inhibited the expression of iNOS resulting from the proinflammatory stimulation. IL‐10 was more effective than IL‐4 in suppressing iNOS expression and, interestingly, IL‐10 conferred protection against oligodendroglial death evoked by LPS/IFN‐γ. Our data raise the question of whether IL‐10 may play a protective role in demyelinating diseases, not only downregulating the function of inflammatory cells but also promoting survival of progenitors and differentiated oligodendrocytes.
Suppression of the induction of long‐term depression by carbon monoxide in rat cerebellar slices
Authors: Shibuki Katsuei , Kimura Shinji , Wakatsuki Hidemitsu 
Published: March 2003

AbstractCarbon monoxide (CO) suppresses brain functions at doses lower than that suppressing oxygen (O2) supply to the brain, and the cerebellum is one of the sites most susceptible to the neurotoxic effects of CO. We investigated the effects of CO on the induction of cerebellar long‐term depression (LTD) in the synapses between parallel fibres (PFs) and Purkinje cells. CO, at concentrations between 8 nm and 5 µm, exhibited almost no effect on synaptic responses in Purkinje cells, O2 consumption and NO release from PFs in rat cerebellar slices. However, the induction of LTD was significantly suppressed by CO at concentrations between 40 and 200 nm. The suppressive effect of 40 nm CO was antagonized by 10 µm NOR3, an NO donor. In contrast, CO exhibited no clear effect on the induction of LTD at concentrations between 1 and 5 µm. The induction of LTD, suppressed by 10 µmNG‐nitro‐l‐arginine, an inhibitor of NO synthase, was not restored by 5 µm CO. CO is not only a neurotoxic substance but also a candidate for an intercellular messenger. δ‐Aminolevulinate (30 µm), a substance facilitating endogenous CO production, suppressed the induction of LTD, and the effect of δ‐aminolevulinate was antagonized by 10 µm NOR3. These findings suggest that CO may have a suppressive effect on the induction of cerebellar LTD at nanomolar concentrations, probably via its effects on NO/cGMP signalling.
The dorsomedial visual areas in New World and Old World monkeys: homology and function
Authors: Rosa Marcello G. P. , Tweedale Rowan 
Published: March 2003

AbstractThe extrastriate cortex near the dorsal midline has been described as part of an ‘express’ pathway that provides visual input to the premotor cortex. This pathway is considered important for the integration of sensory information about the visual field periphery and the skeletomotor system, especially in relation to the control of arm movements. However, a better understanding of the functional contributions of different parts of this complex has been hampered by the lack of data on the extent and boundaries of its constituent visual areas. Recent studies in macaques have provided the first detailed view of the topographical organization of this region in Old World monkeys. Despite differences in nomenclature, a comparison of the visuotopic organization, myeloarchitecture and connections of the relevant visual areas with those previously studied in New World monkeys reveals a remarkable degree of similarity and helps to clarify the subdivision of function between different areas of the dorsomedial complex. A caudal visual area, named DM or V6, appears to be important for the detection of coherent patterns of movement across wide regions of the visual field, such as those induced during self‐motion. A rostral area, named M or V6A, is more directly involved with visuomotor integration. This area receives projections both from DM/V6 and from a separate motion analysis channel, centred on the middle temporal visual area (or V5), which detects the movement of objects in extrapersonal space. These results support the suggestion, made earlier on the basis of more fragmentary evidence, that the areas rostral to the second visual area in dorsal cortex are homologous in all simian primates. Moreover, they emphasize the importance of determining the anatomical organization of the cortex as a prerequisite for elucidating the function of different cortical areas.
Stretch‐activated cation channels of leech neurons exhibit two activity modes
Authors: Pellegrini Monica , Menconi M. Carla , Pellegrino Mario 
Published: March 2003

AbstractSingle‐channel recordings were used to characterize two activity modes of stretch activated channels (SACs) in identified neurons of the leech. Clear‐cut differences in the activity pattern of SACs from freshly desheathed cell bodies and from cultured AP cells were observed. SACs of inside‐out patches, made by ‘gentle’ sealing and excised from cell bodies of freshly desheathed ganglia exhibited spike‐like (SL) activity, with a mean channel open time (MCOT) shorter than 10 ms. Fitting of dwell open‐time distributions revealed time constants shorter than 2 and 10 ms. This activity was characterized by a chord conductance of about 115 pS. SACs from cultured cells often displayed activity just after excision. MCOT exceeded 200 ms and the time constants of open‐time interval distributions were longer than 10 and 100 ms. Furthermore, this activity pattern was characterized by both sub‐ (about 80 and 40 pS) and super‐conductance (150 pS) levels, hence denoted as multiconductance (MC) mode. The percentage of open time spent at the main subconductance level (80 pS) was significantly higher in patches isolated from growth cones than in those from cell bodies of cultured neurons. The two activity modes (SL and MC) should belong to the same channel because both modes have a common main conductance value and exhibit outward rectification, stretch sensitivity and blockage by Gd3+ and gentamicin.     Cytochalasin D applied to the cytoplasmic side induced activation of SACs or increased their ongoing activity. Thus, the observed differences in the expression of the two activity modes of SACs might be associated with different arrangements of the cortical cytoskeleton.
Nitric oxide induces cGMP immunoreactivity and modulates membrane conductance in identified central neurons of Aplysia
Authors: Koh H.‐Y. , Jacklet J. W. 
Published: March 2003

AbstractNitric oxide (NO) acts as an orthograde neurotransmitter in the central nervous system by stimulating guanylyl cyclase and increasing cGMP. We previously demonstrated this pathway for an identified synaptic follower neuron in the cerebral ganglion of the mollusc Aplysia californica. Here, we investigated the NO–cGMP pathway in other Aplysia central neurons using cGMP immunocytochemistry and intracellular recordings. NO‐induced cGMP immunoreactivity in a few neurons in the abdominal, pleural and buccal ganglia, including identified neurons L11 and R15 in the abdominal ganglion and neuron Bng in the buccal ganglion. NO depolarized all these neurons but none of the four nonimmunoreactive neurons tested. In neuron L11, NO‐induced depolarization, tonic spiking and a reduction in membrane conductance at resting potential. The NO effect was mimicked by applying the membrane permeable analogue, 8‐Br‐cGMP in L11. Neuron R15 was depolarized and its activity shifted from spike/bursts to tonic spiking. These NO effects were blocked by applying the guanylyl cyclase inhibitor ODQ and mimicked by 8‐Br‐cGMP. Neuron Bng was depolarized and produced spikes tonically. These results provide evidence that the NO–cGMP pathway is linked to membrane ionic channels in cGMP‐IR neurons, and the channels may be different in specific neurons.
Lowering the extracellular potassium concentration elicits epileptic activity in neocortical tissue of epileptic patients
Authors: Gorji Ali , Köhling Rüdiger , Straub Heidrun , Höhling Jörg‐Michael , Madeja Michael 
Published: March 2003

AbstractThe increase in the extracellular potassium concentration ([K+]o) is a well‐established model of epilepsy (the so‐called high potassium model). Therefore, it is generally accepted that for the prevention of abnormal excitability and seizure generation, increases of [K+]o must be avoided. In this paper, however, we show that on the contrary, a reduction of [K+]o also elicits epileptic activity in brain slices of man.
NMDA receptor antagonist treatment induces a long‐lasting increase in the number of proliferating cells, PSA‐NCAM‐immunoreactive granule neurons and radial glia in the adult rat dentate gyrus
Authors: Nacher Juan , Rosell Daniel R. , Alonso‐Llosa Gregori , McEwen Bruce S. 
Published: March 2003

AbstractDuring adulthood, neural precursors located in the subgranular zone of the dentate gyrus continue to proliferate, leading to the generation of new granule neurons. These recently generated cells transiently express the polysialylated form of the neural cell adhesion molecule, PSA‐NCAM, and are supported by radial glia‐like cells that are likely to play a role in neuronal migration and differentiation, or even act as their precursors. Previous reports indicate that treatment with NMDA receptor antagonists stimulates adult neurogenesis in the dentate gyrus, and because of the potential therapeutic value of this approach, we were interested in further characterizing the consequences of pharmacologically modulating this process. We treated adult rats with the competitive NMDA receptor antagonist, CGP43487, and examined cell proliferation, PSA‐NCAM expression, and changes in the radial glia cell population in the subgranular zone at different time points. In addition, we sought to determine if this treatment led to changes in cell death or gliotic reactions. The number of proliferating cells in the subgranular region of the dentate gyrus was increased significantly 2 days after treatment and it remained elevated 7 days postinjection. PSA‐NCAM‐immunoreactive granule cells and nestin‐expressing radial glia‐like cells also increased in number 7 days after the treatment. In contrast, we did not observe any change in granule cell death, and we were unable to detect any microglial or astroglial reaction during the first 7 days after treatment. Thus, NMDA receptor antagonist treatment serves as a valuable tool to increase neurogenesis in the adult hippocampus without undesirable collateral deleterious effects.
Effects of substance P on excitability and ionic currents of normal and axotomized rat dorsal root ganglion neurons
Authors: Abdulla F. A. , Stebbing M. J. , Smith P. A. 
Published: March 2003

AbstractSubstance P (SP) may act within dorsal root ganglia (DRG) to modulate the transmission of nociceptive information. Because peripheral nerve injury (axotomy) alters the peptide content of sensory neurons, we used whole‐cell recording to examine the effects of sciatic nerve section on the sensitivity of rat lumbar DRG neurons to SP (0.3–1 µm). At 1 µm, SP increased the excitability of ‘small’, putative nociceptive neurons but had little effect on the excitability of ‘large’ neurons. Two‐four weeks after sciatic nerve section, however, the effect of SP on ‘large’ axotomized neurons was increased and its effect on ‘small’ neurons was decreased. SP did not affect Ca2+ channel currents in control or axotomized neurons. The effects of SP on the current‐voltage (I–V) relationship of 77% of neurons involved increased inward current at potentials below −30 mV and suppressed outward current at potentials above −20 mV. The effects of SP on the I–V relationship were similar in control and in axotomized neurons and the altered sensitivity of ‘small’ and ‘large’ cells could not be attributed to axotomy‐induced changes in input resistance or membrane potential. The possible relevance of alterations in sensitivity, of ‘large’ DRG neurons to SP, to the generation of neuropathic pain is discussed.
Characteristics of fast Na+ current of hypoglossal motoneurons in a rat brainstem slice preparation
Authors: Lape Remigijus , Nistri Andrea 
Published: March 2003

AbstractWhole‐cell patch clamp recordings were performed on hypoglossal motoneurons in a brainstem slice preparation from the neonatal rat brain to study the characteristics of the fast Na+ current (INa) which has not been hitherto investigated in these cells. To aid voltage clamping of INa, cells were bathed in low Na+ solution, loaded intracellularly with Na+ (to reverse the Na+ gradient) or treated with a small dose (20 nm) of tetrodotoxin. In low extracellular Na+ solution (Na+ was replaced by choline or N‐methyl‐d‐glucamine) INa activated at membrane potentials positive to −45 mV and was half‐maximally activated at −30 mV. Similar data were obtained when the Na+ gradient was reversed or tetrodotoxin was applied. INa rapidly activated (1–3.5 ms time constant) and inactivated (1.6 ms time constant at 0 mV) during membrane depolarization. Inactivation was strongly voltage‐dependent (half inactivation at −44 mV) and developed mono‐exponentially. Recovery from inactivation was bi‐exponential with fast and slow time constants of 14 and 160 ms, respectively, at −58 mV. The rapid turning on of INa was presumably responsible for the upstroke of the fast action potential generated by these cells while the slow phase of recovery from inactivation might modulate the ability to fire repetitively at high rate.
Mismatch between BDNF mRNA and protein expression in the developing visual cortex: the role of visual experience
Authors: Tropea Daniela , Capsoni Simona , Tongiorgi Enrico , Giannotta Sabina , Cattaneo Antonino , Domenici Luciano 
Published: March 2003

AbstractBrain‐derived neurotrophic factor (BDNF) messenger RNA (mRNA) expression in the rat visual cortex of young and postnatal day 90 (P90) animals is developmentally regulated and influenced by visual experience. In the present paper we compared the expression of BDNF mRNA to the actual changes of BDNF protein occurring during postnatal development and verified whether BDNF protein distribution is controlled by visual activity. To achieve this aim we analysed BDNF mRNA and/or BDNF protein cellular distribution in the rat visual cortex at different postnatal ages by using immunohistochemistry and highly sensitivein situhybridization. We found that before eye opening (P13), in all cortical layers a large number of visual cortical neurons contain BDNF mRNA with no detectable amount of BDNF protein. At later ages (P23 and P90), the number of BDNF‐immunostained cells increases; most neurons are double labelled for BDNF mRNA and protein, and a small group of neurons is labelled only for BDNF protein. The cellular increase of BDNF immunolabelling is blocked in animals deprived of visual experience from birth (dark rearing), with a large population of neurons containing BDNF mRNA but not BDNF protein. This is similar to what is observed before eye opening. Exposure of dark‐reared rats to a brief period (2 h) of light restores a good match between BDNF mRNA and BDNF protein cellular expression. We propose that visual experience controls the neuronal content of BDNF mRNA and BDNF protein in developing visual cortex.
Vasoactive intestinal polypeptide (VIP) phase‐shifts the rat suprachiasmatic nucleus clock in vitro
Authors: Reed Helen E. , Meyer‐Spasche Alert , Cutler David J. , Coen Clive W. , Piggins Hugh D. 
Published: March 2003

AbstractIn mammals, the principal circadian pacemaker is housed in the hypothalamic suprachiasmatic nuclei (SCN). The SCN exhibit high levels of vasoactive intestinal polypeptide (VIP) immunoreactivity and two of the three VIP receptors, VPAC2 and PAC1, are found in the rat SCN. However, the role of VIP in the SCN remains unclear. In this study, we examined the phase‐resetting actions of VIP and selective VIP receptor agonists on the electrical activity rhythm of rat SCN neurons in vitro. Application of VIP during the subjective day did not shift the peak in the firing rate rhythm. However, VIP treatment during the early or late subjective night evoked a small phase delay or a large phase advance, respectively. The phase‐advancing effect of VIP was reproduced by the novel VPAC2 receptor agonist RO 25‐1553, but not by pituitary adenylate cyclase‐activating peptide (a potent PAC1 receptor agonist), or by [K15,R16,L27]VIP(1‐7)/GRF(8‐27), a novel, selective VPAC1 receptor agonist. These data show that VIP phase‐dependently phase‐resets the rodent SCN pacemaker in vitro, presumably via the VPAC2 receptor. As the pattern of phase‐shifting evoked by VIP and RO 25‐1553 resembles the phase‐resetting actions of light on rodent behavioural rhythms, these data support a role for VIP and the VPAC2 receptor in photic entrainment of the rodent circadian pacemaker.
Differential daily expression of Per1 and Per2 mRNA in the suprachiasmatic nucleus of fetal and early postnatal mice
Authors: Shimomura Haruka , Moriya Takahiro , Sudo Motoki , Wakamatsu Hisanori , Akiyama Masashi , Miyake Yoshiaki , Shibata Shigenobu 
Published: March 2003

AbstractIt is well known that there are circadian rhythms of 2‐deoxyglucose uptake and neuronal firing in the rat suprachiasmatic nucleus (SCN) during fetal and early postnatal periods. A core clock mechanism in the mouse SCN appears to involve a transcriptional feedback loop in which CLOCK and BMAL1 function as positive regulators and three mPeriod (mPer) genes play a role in negative feedback. Per genes expression occurs not only in the adult SCN but also in the fetal SCN. However, the developmental change in these genes remains unclear. In this experiment, we examined the day–night pattern of expression of Per1 and Per2 mRNA in the mouse SCN and cerebral cortex on embryonic day 17, postnatal day 3, and in young adult mice under a light–dark cycle. Daily rhythms of mRNA content were observed in mPer1 but not mPer2 in the fetal SCN. Interestingly, the expression of mPer2 in the SCN was high throughout the entire day, and a significant daily rhythm of this gene was observed on postnatal day 6. The expression pattern of SCN mPer1 in constant darkness was similar to that seen in the light–dark cycle. The present results suggest that the daily oscillation of mPer1 but not of mPer2 in the SCN in fetal and early postnatal mice may be associated with the daily rhythms of 2‐deoxyglucose uptake and neuronal firing.
Neural cell adhesion molecule is endocytosed via a clathrin‐dependent pathway
Authors: Miñana R. , Duran J. M. , Tomas M. , Renau‐Piqueras J. , Guerri C. 
Published: March 2003

AbstractNeural cell adhesion molecule (NCAM) constitutes a group of cell surface glycoproteins that regulate cell–cell interactions in the developing and adult brain. Endocytosis is a mechanism which dynamically controls the amount of cell surface NCAM expression and may involve the rapid changes occurring in NCAM expression under certain physiological or pathological conditions. However, the endocytic pathway of NCAM is presently unknown. Using astrocytes in culture and immunofluorescence we show that NCAM is internalized and that the immunolabelling presents a high degree of colocalization with clathrin, α‐adaptin and transferrin, suggesting that NCAM is endocytosed by a clathrin‐dependent pathway. Potassium depletion which disrupts clathrin‐mediated endocytosis, inhibited internalization of NCAM. Electron microscopy and immunogold studies also demonstrate that the surface of clathrin‐coated vesicles are also immunolabelled for both α‐adaptin and PSA‐NCAM, the highly sialylated isoform of NCAM. Furthermore, immunoprecipation studies demonstrate that NCAM is associated with both clathrin and α‐adaptin, a component of adaptor complex AP‐2, in brain, neurons and astrocytes. These findings indicate that NCAM is mainly endocytosed via clathrin‐coated vesicles, suggesting a possible mechanism that may contribute to the rapid changes in NCAM expression at the cell surface.
Swelling‐activated calcium signalling in cultured mouse primary sensory neurons
Authors: Viana Félix , De La Peña Elvira , Pecson Brian , Schmidt Robert F. , Belmonte Carlos 
Published: March 2003

AbstractThe effects of hypo‐osmotic membrane stretch on intracellular calcium concentration ([Ca2+]i), cell volume and cellular excitability were investigated in cultured mouse primary sensory trigeminal neurons. Hypotonic solutions (15–45%) led to rapid cell swelling in all neurons. Swelling was accompanied by dose‐dependent elevations in [Ca2+]i in a large fraction of neurons. Responses could be classified into three categories. (i) In 57% of the neurons [Ca2+]i responses had a slow rise time and were generally of small amplitude. (ii) In 21% of the neurons, responses had a faster rise and were larger in amplitude. (iii) The remaining cells (22%) did not show [Ca2+]i responses to hypo‐osmotic stretch. Slow and fast [Ca2+]i changes were observed in trigeminal neurons of different sizes with variable responses to capsaicin (0.5 µm). The swelling‐induced [Ca2+]i responses were not abolished after depletion of intracellular Ca2+ stores with cyclopiazonic acid or preincubation in thapsigargin, but were suppressed in the absence of external Ca2+. They were strongly attenuated by extracellular nickel and gadolinium. Hypotonic stimulation led to a decrease in input resistance and to membrane potential depolarization. Under voltage‐clamp, the [Ca2+]i elevation produced by hypotonic stimulation was accompanied by the development of an inward current and a conductance increase. The time course and amplitude of the [Ca2+]i response to hypo‐osmotic stimulation showed a close correlation with electrophysiological properties of the neurons. Fast [Ca2+]i responses were characteristic of trigeminal neurons with short duration action potentials and marked inward rectification. These findings suggest that hypo‐osmotic stimulation activates several Ca2+‐influx pathways, including Gd3+‐sensitive stretch‐activated ion channels, in a large fraction of trigeminal ganglion neurons. Opening of voltage‐gated Ca2+ channels also contributes to the response. The pattern and rate of Ca2+ influx may be correlated with functional subtypes of sensory neurons.