bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cajal‐Retzius cells in early postnatal mouse cortex selectively express functional metabotropic glutamate receptors
Authors: Martínez‐Galán Juan Ramón , López‐Bendito Guillermina , Luján Rafael , Shigemoto Ryuichi , Fairén Alfonso , Valdeolmillos Miguel 
Published: March 2003

AbstractGlutamate receptors have been linked to the regulation of several developmental events in the CNS. By using cortical slices of early postnatal mice, we show that in layer I cells, glutamate produces intracellular calcium ([Ca2+]i) elevations mediated by ionotropic and metabotropic glutamate receptors (mGluRs). The contribution of mGluRs to these responses was demonstrated by application of tACPD, an agonist to groups I and II mGluRs, which evoked [Ca2+]i increases that could be reversibly blocked by MCPG, an antagonist to groups I and II mGluRs. In the absence of extracellular Ca2+, repetitive applications of tACPD or quisqualate, an agonist to group I mGluRs, elicited decreasing [Ca2+]i responses that were restored by refilling a thapsigargin‐sensitive Ca2+ store. The use of specific group I mGluR agonists CHPG and DHPG indicated that the functional mGluR in layer I was of the mGluR1 subtype. Subtype specific antibodies confirmed the presence of mGlur1α, but not mGluR5, in Cajal‐Retzius (Reelin‐immunoreactive) neurons.
Oxygen modulates cell death in the proliferating retina
Authors: Semo Maayan , Bryce Jennifer , Jeffery Glen 
Published: March 2003

AbstractMany factors probably regulate the process of natural cell death during development. It is present in both the early undifferentiated retina and later following differentiation. Melanin production plays a role in regulating retinal development and when it is absent, cell proliferation and death are enhanced. Here we examine the effects of hyperoxia on this process, as oxygen has been shown to reduce cell death among differentiated photoreceptors late in development. However, in this study we examine its effects much earlier in pigmented and albino pigmentation phenotypes, when most cells are still actively dividing and are not committed to a specific fate. Newborn mice were exposed to high oxygen levels for 24 h and then returned to normal air for varying periods and their retinae examined. Hyperoxia had a dramatic effect on the number of dying cells, reducing them by almost 60% in pigmented animals and by over 80% in albinos. Following the return to normal air there was a gradual increase in their number over 360 min back to normal levels in pigmented mice; however, in albinos there was a complete rebound in levels of cell death within 40 min, reflecting the increased metabolic stress present in albino retinae due to their abnormal levels of proliferation. These results highlight the important role played by oxygen during early natural cell death in the retina and reveal the different developmental conditions present in the retinae of the two pigmentation phenotypes examined.
Central monoamine and plasma corticosterone changes induced by a bacterial endotoxin: sensitization and cross‐sensitization effects
Authors: Hayley Shawn , Lacosta Susan , Merali Zul , Van Rooijen Nico , Anisman Hymie 
Published: March 2003

AbstractLow doses of lipopolysaccharide, tumour necrosis factor‐alpha (TNF‐α), interleukin‐1β (IL‐1β), or exposure to a stressor (restraint) increased plasma corticosterone levels. In animals pretreated with lipopolysaccharide, a marked sensitization of the corticosterone response was evident upon subsequent exposure to lipopolysaccharide, TNF‐α, or restraint, 1 day later. As well, the sickness‐inducing effects of lipopolysaccharide, TNF‐α and IL‐1β were markedly increased in mice pretreated with lipopolysaccharide. The sensitization effects were marked when the second treatment was administered 1 day after lipopolysaccharide administration, but not when a 28‐day interval elapsed. In a second experiment, TNF‐α influenced monoamine functioning in the paraventricular nucleus of the hypothalamus and within extrahypothalamic regions, including the central amygdala, locus coeruleus, prefrontal cortex. Moreover, serotonin activity within the central amygdala, as well as dopamine activity within the prefrontal cortex, were subject to a sensitization effect in animals pretreated with lipopolysaccharide 1 day earlier. Macrophage depletion by a suspension of clodronate liposomes attenuated the plasma corticosterone changes induced by TNF‐α, but did not affect the sensitization. In contrast, the acute effects of TNF‐α on central neurotransmitters were unaffected by the liposome suspension, but this treatment prevented the sensitization. These data may be relevant to clinical situations in which individuals exposed to bacterial infections may be rendered more susceptible to the behavioural and neurochemical effects of subsequently encountered stressors and immunological challenges.
NMDA‐induced phosphorylation of the microtubule‐associated protein MAP‐2 is mediated by activation of nitric oxide synthase and MAP kinase
Authors: Llansola Marta , Sáez Rosana , Felipo Vicente 
Published: March 2003

AbstractMicrotubule‐associated protein MAP‐2 is a neuronal phosphoprotein which modulates microtubule stability and spatial organization of signal transduction pathways. The functions of MAP‐2 are modulated by phosphorylation. We studied the modulation of MAP‐2 phosphorylation using the N‐methyl‐d‐aspartate (NMDA) type of glutamate receptors and the signal transduction pathways mediating this modulation in primary cultures of rat cerebellar neurons. NMDA induced a rapid increase (330% of basal at 5 min) in MAP‐2 phosphorylation which was not prevented by KN‐62, indicating that it is not mediated by activation of Ca‐calmodulin‐dependent protein kinase. NMDA‐induced phosphorylation of MAP‐2 was inhibited by the nitric oxide synthase inhibitors nitroarginine and 7‐nitroindazole and by PD098059 (an inhibitor of MAP kinase kinase), but was only slightly reduced by calphostin C or U‐73122, inhibitors of protein kinase C and of phospholipase C, respectively. This indicates that the main pathway mediating NMDA‐induced phosphorylation of MAP‐2 is activation of nitric oxide synthase and subsequent activation of MAP kinase. We show that activation of NMDA receptors induces an activation of MAP kinase which is prevented by nitroarginine. The nitric oxide‐generating agent (±)‐S‐nitroso‐N‐acetylpenicillamine (SNAP) also induced activation of MAP kinase and increased phosphorylation of MAP‐2. Other nitric oxide‐generating agents (NOC‐18 and NOR‐3) also increased MAP‐2 phosphorylation. The interplay between NMDA receptors‐associated signal transduction pathways and MAP‐2 may be involved in the modulation of neuronal responses to extracellular signals and in the regulation of neuronal function.
Phorbol esters promote postsynaptic accumulation of Vesl‐1S/Homer‐1a protein
Authors: Kato Akihiko , Fukuda Takaichi , Fukazawa Yugo , Isojima Yasushi , Fujitani Kazuko , Inokuchi Kaoru , Sugiyama Hiroyuki 
Published: March 2003

AbstractWe examined effects of phorbol esters on the amount and the subcellular distribution of the activity‐regulated protein Vesl‐1S/Homer‐1a in cultured hippocampal neurons. Major Vesl‐1S immunoreactivity (IR) was detected throughout neuronal somata under control conditions. Bath application of phorbol esters, PMA and PDBu resulted in the increase in the amount of Vesl‐1S proteins and promoted punctate distribution of Vesl‐1S IR at the cortical regions of the neuronal somata. Immunofluorescent observations using antisynaptophysin and anti‐Vesl‐1S antibodies, and electron microscopic observations, revealed that Vesl‐1S accumulated at postsynaptic regions following PMA application. Membrane depolarization with high concentrations of external potassium also promoted the punctate distribution of Vesl‐1S IR. These results demonstrate that phorbol‐triggered reaction cascades result in the accumulation of Vesl‐1S protein at postsynaptic regions, and suggest that these phorbol effects may mimic those caused by synaptic activities.
Parallel fibre receptive fields of Purkinje cells and interneurons are climbing fibre‐specific
Authors: Ekerot Carl‐Fredrik , Jörntell Henrik 
Published: March 2003

AbstractIn cats decerebrated at the intercollicular level, the cutaneous parallel fibre receptive fields of Purkinje cells, molecular layer interneurons and Golgi cells in the cerebellar C3 zone were delineated by natural stimulation of the skin during extracellular unitary recordings. The locations of these receptive fields were compared with the climbing fibre receptive field of the local Purkinje cell and with the receptive fields of other neurons located along a beam of parallel fibres. The parallel fibre receptive fields of these neurons were highly specific to the local climbing fibre receptive field. In Purkinje cells, the parallel fibre receptive fields were located outside the climbing fibre receptive field of the same cell. In contrast, the parallel fibre receptive fields of interneurons were similar to the receptive field of the locally terminating climbing fibres. In both types of neurons, the parallel fibre receptive fields were small and had distinct borders. The location on the skin of the parallel fibre receptive fields differed conspicuously between neighbouring Purkinje cells and between neighbouring interneurons along a beam as well as between Purkinje cells and interneurons in the same electrode tracks. The remarkable specificity between the parallel fibre receptive fields in Purkinje cells and interneurons and the receptive field of the local climbing fibre is most easily explained by different forms of parallel fibre synaptic plasticity.
Neurotrophins act at presynaptic terminals to activate synapses among cultured hippocampal neurons
Authors: Collin Carlos , Vicario‐Abejon Carlos , Rubio Maria E. , Wenthold Robert J. , McKay Ronald D. G. , Segal Menahem 
Published: March 2003

AbstractWe have recently demonstrated that embryonic E16 hippocampal neurons grown in cultures are unable to form fast synaptic connections unless treated with BDNF or NT‐3. This experimental system offers an opportunity to define the roles of neurotrophins in processes leading to formation of functional synaptic connections. We have used ultrastructural and electrophysiological methods to explore the cellular locations underlying neurotrophin action on synaptic maturation. The rate of spontaneous miniature excitatory postsynaptic currents (mEPSCs) evoked by hyperosmotic stimulation was 7–16‐fold higher in neurotrophin‐treated cells than in controls. In addition, the potent neurotransmitter‐releasing drug α‐latrotoxin was virtually ineffective in the control cells while it stimulated synaptic events in neurotrophin‐treated cells. Likewise, the membrane‐bound dye FM1‐43 was taken up by terminals in neurotrophin‐treated cultures five‐fold more than in controls. Both the total number and the number of docked synaptic vesicles were increased by neurotrophin treatment. Activation of synaptic responses by neurotrophins occurred even when postsynaptic glutamate receptors and action potential discharges were pharmacologically blocked. These results are consistent with a presynaptic locus of action of neurotrophins to increase synaptic vesicle density which is critical for rapid synaptic transmission. They also suggest that neurotrophins can activate synapses in the absence of pre‐ and postsynaptic neuronal activity.
Nicotine regulates 5‐HT1A receptor gene expression in the cerebral cortex and dorsal hippocampus
Authors: Kenny Paul J. , File Sandra E. , Rattray Marcus 
Published: March 2003

AbstractThe 5‐HT1A receptor has previously been shown to be important in mediating the behavioural effects of nicotine. It is possible that nicotine administration might regulate the levels of 5‐HT receptors in limbic and cortical regions, and such regulations may underlie adaptive responses to nicotine in the central nervous system. The effects of acute and chronic systemic (–)‐nicotine administration on 5‐HT1A receptor gene expression were measured by in situ hybridization, in the rat cerebral cortex, dorsal hippocampus and lateral septum. In the cortex, acute nicotine (0.5 mg/kg i.p.) significantly increased the expression of 5‐HT1A receptor mRNA 2 h and 24 h after injection. Similarly, acute nicotine significantly increased 5‐HT1A receptor mRNA in the dentate gyrus (DG), CA3 and CA1 regions of the dorsal hippocampus 2 h and 24 h after injection. Acute nicotine was without effect in the lateral septum. Chronic nicotine (0.5 mg/kg i.p; twice daily for 7 days) significantly decreased 5‐HT1A receptor mRNA in the cortex 2 h after the final injection, but was without effect at 24 h or 72 h. Chronic nicotine caused no changes in 5‐HT1A mRNA in the lateral septum or dorsal hippocampus. These data demonstrate that nicotine regulates 5‐HT1A receptor gene expression in the cortex and hippocampus. The rapid regulation of expression of 5‐HT1A receptor mRNA leads to the hypothesis that nicotine‐induced 5‐HT release may alter the postsynaptic sensitivity to 5‐HT.
Induction of neonatal sodium channel II and III α‐isoform mRNAs in neurons and microglia after status epilepticus in the rat hippocampus
Authors: Aronica Eleonora , Yankaya Bulent , Troost Dirk , Van Vliet Erwin A. , Da Silva Fernando H. Lopes , Gorter Jan A. 
Published: March 2003

AbstractSodium channels (NaChs) regulate neuronal excitability in both physiological and pathological conditions, including epilepsy and are therefore an important target for antiepileptic drugs. In the present study, we examined the distribution of mRNAs encoding neonatal NaChs II and III α‐isoforms in control rat hippocampus and after electrically‐induced status epilepticus (SE), using nonradioactive in situ hybridization (ISH). Only weak expression of neonatal NaCh II and III mRNAs was observed in control hippocampus. By contrast, increased expression of neonatal NaCh II and III mRNAs was observed 4 h after the induction of SE in neurons of CA1–CA3 and the dentate granule cell layer. These changes were detected only in rats in which SE was successfully induced and persisted, although less intense, for up to 3 months, when rats display spontaneous seizures. Strong expression of neonatal NaCh α‐isoforms was observed 1 week after SE in microglial cells, as confirmed by double labelling, combining ISH with immunocytochemistry for microglia markers. The increased expression of neonatal isoforms of the NaCh in both neurons and microglial cells may represent a critical mechanism for modulation of neuronal excitability, glial function and pharmacological response to antiepileptic drugs in the course of epileptogenesis.
Brain extracellular glucose assessed by voltammetry throughout the rat sleep–wake cycle
Authors: Netchiporouk L. , Shram N. , Salvert D. , Cespuglio R. 
Published: March 2003

AbstractIn the present study, cortical extracellular levels of glucose were monitored for the first time throughout the sleep–wake states of the freely moving rat. For this purpose, polygraphic recordings (electroencephalogram of the fronto‐occipital cortices and electromyogram of the neck muscles) were achieved in combination with differential normal pulse voltammetry (DNPV) using a specific glucose sensor. Data obtained reveal that the basal extracellular glucose concentration in the conscious rat is 0.59 ± 0.3 mm while under chloral hydrate anaesthesia (0.4 g/kg, i.p.) it increases up to 180% of its basal concentration. Regarding the sleep–wake cycle, the existence of spontaneous significant variations in the mean glucose level during slow‐wave sleep (SWS = +13%) and paradoxical sleep (PS = −11%) compared with the waking state (100%) is also reported. It is to be noticed that during long periods of active waking, glucose level tends towards a decrease that becomes significant after 15 min (active waking = −32%). On the contrary, during long episodes of slow‐wave sleep, it tends towards an increase which becomes significant after 12 min (SWS = +28%). It is suggested that voltammetric techniques using enzymatic biosensors are useful tools allowing direct glucose measurements in the freely moving animal. On the whole, paradoxical sleep is pointed out as a state highly dependent on the availability of energy and slow‐wave sleep as a period of energy saving.
Ca2+ signalling and changes of mitochondrial function during low‐Mg2+‐induced epileptiform activity in organotypic hippocampal slice cultures
Authors: Kovacs R. , Schuchmann S. , Gabriel S. , Kardos J. , Heinemann U. 
Published: March 2003

AbstractSeveral lines of evidence indicate that augmented neuronal activity is associated with increased mitochondrial function, however, the mechanisms of coupling are still unclear. In this study we used a low extracellular Mg2+ concentration and short stimulus trains to evoke neuronal hyperactivity in the form of seizure‐like events (SLE) in hippocampal slice cultures. Simultaneous microfluorimetric and electrophysiological techniques were applied to gain insight into changes of Ca2+ concentration in different compartments and into mitochondrial function. SLEs were associated with a large decrease of the extracellular Ca2+ concentration ([Ca2+]e), a spiking increase of the cytoplasmic and a smoothed elevation of the mitochondrial Ca2+ concentration (cytoplasmic concentration [Ca2+]i; intramitrochondrial concentration [Ca2+]m). Following an initial apparent decline in the mitochondrial membrane potential (ΔΨ) and NAD(P)H autofluorescence, mitochondria depolarized and NADH production was augmented. Furthermore, SLEs were associated with increased oxidation of dihydroethidine (HEt). Our data suggest that intramitochondrial Ca2+ accumulation stimulates NADH production and production of radical oxygen species (ROS). Interestingly, mitochondrial depolarization followed [Ca2+]i and [Ca2+]m changes with a delay implying that electrogenic extrusion of Ca2+ from the mitochondrial matrix might be responsible for the depolarization of the mitochondrial membrane.
BDNF reduces miniature inhibitory postsynaptic currents by rapid downregulation of GABAA receptor surface expression
Authors: Brünig Ina , Penschuck Silke , Berninger Benedikt , Benson Jack , Fritschy Jean‐Marc 
Published: March 2003

AbstractChanges in neurotransmitter receptor density at the synapse have been proposed as a mechanism underlying synaptic plasticity. Neurotrophic factors are known to influence synaptic strength rapidly. In the present study, we found that brain‐derived neurotrophic factor (BDNF) acts postsynaptically to reduce γ‐aminobutyric acid (GABA)‐ergic function. Using primary cultures of rat hippocampal neurons, we investigated the effects of BDNF on GABAergic miniature inhibitory postsynaptic currents (mIPSCs) and on the localization of GABAA receptors. Application of BDNF (100 ng/mL) led within minutes to a marked reduction (33.5%) of mIPSC amplitudes in 50% of neurons, recorded in the whole‐cell patch‐clamp mode, leaving frequency and decay kinetics unaffected. This effect was blocked by the protein kinase inhibitor K252a, which binds with high affinity to trkB receptors. Immunofluorescence staining with an antibody against trkB revealed that about 70% of cultured hippocampal pyramidal cells express trkB. In dual labelling experiments, use of neurobiotin injections to label the recorded cells revealed that all cells responsive to BDNF were immunopositive for trkB. Treatment of cultures with BDNF reduced the immunoreactivity for the GABAA receptor subunits‐α2, ‐β2,3 and ‐γ2 in the majority of neurons. This effect was detectable after 15 min and lasted at least 12 h. Neurotrophin‐4 (NT‐4), but not neurotrophin‐3 (NT‐3), also reduced GABAA receptor immunoreactivity, supporting the proposal that this effect is mediated by trkB. Altogether the results suggest that exposure to BDNF induces a rapid reduction in postsynaptic GABAA receptor number that is responsible for the decline in GABAergic mIPSC amplitudes.
Retrograde response of the rat facial motor nucleus to muscle inflammation elicited by phytohaemagglutinin
Authors: Mariotti R. , Tongiorgi E. , Bressan C. , Armellin M. , Kristensson K. , Bentivoglio M. 
Published: March 2003

AbstractTo investigate whether motoneurons react to signals deriving from target inflammation, we studied the facial motor nucleus after injections of phytohaemagglutinin in the snout of adult rats. This plant lectin is a tool widely used to induce proliferation and activation of T lymphocytes, and we observed marked lymphocyte infiltration in the injected facial muscles. Retrograde labelling of motoneurons was not detected after peripheral injections of fluorochrome‐conjugated phytohaemagglutinin. Nitric oxide synthase, revealed by NADPH‐diaphorase histochemistry, OX‐42‐immunoreactive microglia, and expression of the cell death repressor gene bcl‐2, investigated with nonradioactive in situ hybridization and immunohistochemistry, were evaluated in the facial nucleus. Daily phytohaemagglutinin injections for 4 days, mimicking repeated muscle exposure to inflammatory stimuli, resulted after 2‐day survival in NADPH‐diaphorase induction in motoneurons and marked activation of the surrounding microglia. Quantitative image analysis of NADPH‐diaphorase staining, and OX‐42 immunoreactivity and microglial cell counts indicated highly significant increases with respect to saline‐injected control cases. The occurrence of a neuroprotective retrograde response was evaluated monitoring bcl‐2 expression. Following single phytohaemagglutinin administration, bcl‐2 mRNA was significantly upregulated at 6 h in facial motoneurons and returned to basal levels at 24 h. Bcl‐2 immunoreactivity was markedly upregulated at 24 h and was still significantly higher than in controls at 7 days, when concomitant NADPH‐diaphorase induction in motoneurons and microglia activation was also observed. No degenerative features were observed in motoneurons after phytohaemagglutinin injections at the examined time‐points. The data point out that local muscle inflammation retrogradely elicits gene activation in motoneurons and their microenvironment.
Kindling induces transient fast inhibition in the dentate gyrus–CA3 projection
Authors: Gutiérrez Rafael , Heinemann Uwe 
Published: March 2003

AbstractThe granule cells of the dentate gyrus (DG) send a strong glutamatergic projection, the mossy fibre tract, toward the hippocampal CA3 field, where it excites pyramidal cells and neighbouring inhibitory interneurons. Despite their excitatory nature, granule cells contain small amounts of GAD (glutamate decarboxylase), the main synthetic enzyme for the inhibitory transmitter GABA. Chronic temporal lobe epilepsy results in transient upregulation of GAD and GABA in granule cells, giving rise to the speculation that following overexcitation, mossy fibres exert an inhibitory effect by release of GABA. We therefore stimulated the DG and recorded synaptic potentials from CA3 pyramidal cells in brain slices from kindled and control rats. In both preparations, DG stimulation caused excitatory postsynaptic potential (EPSP)/inhibitory postsynaptic potential (IPSP) sequences. These potentials could be completely blocked by glutamate receptor antagonists in control rats, while in the kindled rats, a bicuculline‐sensitive fast IPSP remained, with an onset latency similar to that of the control EPSP. Interestingly, this IPSP disappeared 1 month after the last seizure. When synaptic responses were evoked by high‐frequency stimulation, EPSPs in normal rats readily summate to evoke action potentials. In slices from kindled rats, a summation of IPSPs overrides that of the EPSPs and reduces the probability of evoking action potentials. Our data show for the first time that kindling induces functionally relevant activity‐dependent expression of fast inhibition onto pyramidal cells, coming from the DG, that can limit CA3 excitation in a frequency‐dependent manner.