bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of delayed rectifier K+ conductance in cultured rat cerebellar granule neurons by activation of calcium‐permeable AMPA receptors
Authors: Jones Glyn , Boyd David F. , Yeung Shuk Yin , Mathie Alistair 
Published: March 2003

AbstractActivation of AMPA (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid) receptors in cerebellar granule cells during perforated‐patch whole‐cell recordings activated an inward current at negative voltages which was followed, after a delay, by the inhibition of an outward potassium current at voltages positive to −20 mV. The activated inward current was inwardly rectifying suggesting that the AMPA receptors were Ca2+‐permeable. This was confirmed by direct measurements of intracellular calcium where Ca2+ rises were seen following AMPA receptor activation in Na+‐free external solution. Ca2+ rises were equally large in the presence of 100 μm Cd2+ to block voltage‐gated Ca2+ channels. Specific voltage‐protocols, allowing selective activation of the delayed rectifier potassium current (KV) and the transient A current (KA), showed that kainate inhibited KV, but not to any great extent KA. The inhibition of KV was blocked by the AMPA receptor antagonist CNQX (6‐cyano‐7‐nitroquinoxaline‐2,3‐dione) and was no longer observed when the KV current was abolished with high concentrations of Ba2+. The responses to kainate were not altered by pre‐treating the cells with pertussis toxin, suggesting that the AMPA receptor stimulation of the G‐protein Gi cannot account for the effects observed. Replacing extracellular Na+ with choline did not alter the inhibition of KV by kainate, however, removing extracellular Ca2+ reduced the kainate response. The inhibition of KV by kainate was unaffected by the presence of 100 μm Cd2+. The guanylyl cyclase inhibitor, ODQ (1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one), did not alter kainate inhibition of KV. It is concluded that ion influx (particularly Ca2+ ions) through AMPA receptor channels following receptor activation leads to an inhibition of KV currents in cerebellar granule neurons.
Cell death is prevented in thalamic fields but not in injured neocortical areas after permanent focal ischaemia in mice overexpressing the anti‐apoptotic protein Bcl‐2
Authors: De Bilbao Fabienne , Guarin Ernesto , Nef Patrick , Vallet Philippe , Giannakopoulos Panteleimon , Dubois‐Dauphin Michel 
Published: March 2003

AbstractPrevious studies have suggested that various apoptotic‐related proteins could be involved in the death process induced by cerebral ischaemia. In order to further clarify their role and examine how the anti‐apoptotic protein Bcl‐2 could influence this process, the time‐course of mRNA expression of various cell death genes was studied from 1 to 14 days following permanent occlusion of the middle cerebral artery in wild‐type (WT) and Bcl‐2 transgenic mice, within and outside the area of infarction. No differences of the infarct sizes were observed between the two groups of mice, showing that the extent of neuronal injury could not have been lowered by the Bcl‐2 transgene. Seven days after the ischaemic insult, the mRNA expression of the cell death gene effector cpp32 was dramatically upregulated in the penumbra of WT and Bcl‐2 transgenic mice. Interestingly, the cpp32 transcript was markedly induced from 3 days in the ipsilateral thalamus of the two groups of mice. However, apoptotic bodies were observed in the thalamic field of WT but not transgenic mice. This suggests that cpp32 mRNA may be induced in an attempt to kill the injured cells and, in contrast to the penumbra, cell death in the thalamus may be prevented in Bcl‐2 transgenic mice. Based on these results, the pathophysiological mechanisms that underly neuronal damage following ischaemia need consideration in order to evaluate the extent of neuroprotection that may be afforded by the Bcl‐2 anti‐apoptotic protein. Although the present study does not confirm previous data showing a protective role of Bcl‐2 in neocortical infarcted areas, it suggests that anti‐apoptotic therapies may constitute a possible treatment for areas of the brain remote from those directly affected by ischaemia.
Induction of integrin‐associated protein (IAP) mRNA expression during memory consolidation in rat hippocampus
Authors: Lee Eminy H. Y. , Hsieh Yi P. , Yang Chia L. , Tsai Kuen J. , Liu Cheng H. 
Published: March 2003

AbstractWe have previously demonstrated that hippocampal integrin‐associated protein (IAP) gene expression is associated with memory formation in a one‐way inhibitory avoidance learning in rats. In the present study, we further investigated the role and mechanism of IAP involved in memory consolidation in rats. Because of the minute amount of IAP present in the brain, we have adopted the quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) method. Our results revealed that hippocampal IAP mRNA expression is approximately fourfold higher in rats showing good memory retention (GM, retention score of 600 s) at 3 h, but not at other time points, after training when compared with the poor memory rats (retention score < 80 s). On the other hand, integrin αv mRNA level was markedly increased (∼ twofold), while integrin β3 mRNA level was decreased (∼ 50%) at 1 h post‐training. Further, separate sets of RT‐PCR analysis revealed that IAP5 and IAP6 mRNA expressions, but not that of IAP7, were markedly increased in GM rats 3 h post‐training. Moreover, regional distribution studies revealed that different isoforms of the IAP gene are similarly distributed in different brain areas, while IAP7 has been the predominant form present in astrocyte cells. These results together suggest that IAP mRNA expression is indeed induced upon training, rather than that the GM rats have constitutively higher levels of IAP. The unparallel change of IAP and integrin mRNA expressions as far as time‐course is concerned suggests that they are possibly involved in different forms and stages of memory processing. Further, IAP5 and IAP6 are more closely associated with memory consolidation, while IAP7 may constitute the major isotype for signal transduction in astrocyte cells.
Alterations in Purkinje cell spines of calbindin D‐28 k and parvalbumin knock‐out mice
Authors: Vecellio Marco , Schwaller Beat , Meyer Michael , Hunziker Willi , Celio Marco R. 
Published: March 2003

AbstractThe second messenger Ca2+ is known to act in a broad spectrum of fundamental cell processes, including modifications of cell shape and motility, through the intermediary of intracellular calcium‐binding proteins. The possible impact of the lack of the intracellular soluble Ca2+‐binding proteins parvalbumin (PV) and calbindin D‐28 k (CB) was tested on spine morphology and topology in Purkinje cell dendrites of genetically modified mice. Three different genotypes were studied, i.e. PV or CB single knock‐out (PV–/–, CB–/–) and PV and CB double knock‐out mice (PV–/–CB–/–). Purkinje cells were microinjected with Lucifer Yellow and terminal dendrites scanned at high resolution with a confocal laser microscope followed by three‐dimensional (3‐D) reconstruction. The absence of PV had no significant effect on spine morphology, whereas the absence of CB resulted in a slight increase of various spine parameters, most notably spine length. In double knock‐out mice, the absence of both PV and CB entailed a doubling of spine length, an increase in spine volume and spine surface, a higher spine density along the dendrites, as well as a more clustered spine distribution. In all three genotypes, a reduction in the number of stubby spines was observed compared with wild‐type animals. These results suggest a morphological compensation for the lack of the soluble calcium buffers in the cytoplasm of Purkinje cell dendritic spines. The increase in various spine parameters, particularly volume, may counteract the lack of the calcium buffers, such as to adjust Ca2+‐transients at the transitional zone between spines and dendrites.
Red nucleus lesions impair overground locomotion in rats: a kinetic analysis
Authors: Muir Gillian D. , Whishaw Ian Q. 
Published: March 2003

AbstractThe red nucleus is a prominent brainstem nucleus in mammals which is thought to be involved in production of skilled limb movements. The presence of the red nucleus and associated rubrospinal tract in animals that do not produce skilled limb movements, however, suggests that these structures might also be involved in control of more general limb actions, such as those occurring during locomotion. The present study investigates this question by measuring the three‐dimensional ground reaction forces produced by locomoting rats with unilateral excitotoxic lesions of the red nucleus. Twenty‐four to 48 h after the lesion, rats moved with an asymmetric gait during which abnormal braking and propulsive forces were produced during the dual contact time of the forelimb contralateral to the lesion and the ipsilateral hindlimb. Rats did not recover normal symmetrical locomotion within the 55‐day duration of the study. The persistent asymmetry produced by red nucleus ablation provides the first unequivocal demonstration that the red nucleus plays a role in ongoing overground locomotion in the rat. Species differences in phylogeny and connectivity of the red nucleus are discussed, as well as the possibility that there is a general compensatory response to unilateral CNS injury in the rat.
Alterations in preproenkephalin and adenosine‐2a receptor mRNA, but not preprotachykinin mRNA correlate with occurrence of dyskinesia in normal monkeys chronically treated with l‐DOPA
Authors: Zeng B. ‐Y. , Pearce R. K. B. , MacKenzie G. M. , Jenner P. 
Published: March 2003

AbstractChronic treatment with l‐DOPA induces dyskinesia in patients with Parkinson's disease (PD) and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated monkeys, but is not thought to do so in normal humans or primates. However, we have shown that chronic oral high dose l‐DOPA administration, with the peripheral decarboxylase inhibitor, carbidopa and with or without the peripherally acting catechol‐O‐methyl transferase (COMT) inhibitor, entacapone, to normal macaque monkeys for 13 weeks induced dyskinesia in a proportion of animals. In the present study, in situ hybridization histochemistry was used to investigate the effect of chronic l‐DOPA administration on the activity of the direct and indirect striatal output pathways by measuring striatal preprotachykinin (PPT), preproenkephalin‐A (PPE‐A) and adenosine‐2a (A2a) receptor gene expression in these monkeys. Overall there was no significant difference in striatal PPT, PPE‐A and A2a receptor mRNA levels between normal animals and all l‐DOPA (plus carbidopa and/or entacapone)‐treated animals irrespective of whether or not dyskinesia occurred. However, when the level of PPE‐A and A2a receptor mRNA was analysed in eight monkeys displaying marked dyskinesias as a result of l‐DOPA (plus carbidopa with or without entacapone) treatment, there was a significant increase in PPE‐A and A2a receptor mRNA message levels in the striatum compared with animals receiving identical treatment, but displaying few or no involuntary movements, and compared with normal controls. There was no difference in striatal PPT mRNA levels in monkeys exhibiting severe dyskinesia compared with those showing little or no dyskinesia after l‐DOPA treatment or to normal controls. These results suggest that prolonged l‐DOPA treatment alone has no consistent effect on either the direct or indirect pathways, as judged by striatal PPT, PPE‐A or A2a receptor mRNA levels in normal monkeys. However, in monkeys exhibiting marked dyskinesia resulting from chronic l‐DOPA treatment, abnormal activity is detected in the indirect striato‐pallidal output pathway, as judged by striatal PPE‐A and A2a receptor mRNA levels, indicating an imbalance between the direct and indirect striatal pathway which may explain the emergence of dyskinesia in these animals.
Molecular and functional properties of synaptically activated NMDA receptors in neonatal motoneurons in rat spinal cord slices
Authors: Abdrachmanova Galya , Teisinger Jan , Vlachová Viktorie , Vyklický Ladislav 
Published: March 2003

AbstractThe functional properties of N‐methyl‐ d‐aspartate (NMDA) receptor‐mediated excitatory postsynaptic currents (EPSC) were studied in fluorescence‐labelled motoneurons in thin spinal cord slices. The deactivation of NMDA receptor EPSCs in motoneurons voltage‐clamped at +40 mV was independent of intensity or location of stimulation and of postnatal age [τfast = 28.5 ± 4.6 ms (63.6 ± 8.8%) and τslow = 165.6 ± 49.6 ms]. In the presence of 1 mm Mg2+ the amplitude of NMDA receptor EPSCs was voltage‐dependent. Boltzmann analysis of the relationship between peak NMDA receptor EPSC amplitude and membrane potential suggested an apparent Kd of Mg2+ (at 0 mV) of 0.87 mm. Nonstationary variance analysis of NMDA receptor EPSCs gave an estimated single‐channel conductance of 59 ± 14 pS. Direct measurement of the NMDA receptor channel openings in outside‐out patches isolated from motoneurons indicated the presence of single‐channel conductance levels of 21.8 ± 2.8 pS, 37.1 ± 3.2 pS, 49.6 ± 5.1 pS and 69.6 ± 4.2 pS. Single‐cell RT‐PCR analysis of mRNA revealed that NR1, NR2A–D and NR3A transcripts were expressed in motoneurons. These results suggest that specific assembly of NMDA receptor subunits in motoneurons determines the functional and pharmacological properties of the receptors in these cells.
Transcription factor dynamics and neuroendocrine signalling in the mouse pineal gland: a comparative analysis of melatonin‐deficient C57BL mice and melatonin‐proficient C3H mice
Authors: Von Gall Charlotte , Lewy Alfred , Schomerus Christof , Vivien‐Roels Berthe , Pevét Paul , Korf Horst‐Werner , Stehle Jörg H. 
Published: March 2003

AbstractIn rodents, the nocturnal rise and fall of arylalkylamine N‐acetyltransferase (AANAT) activity controls the rhythmic synthesis of melatonin, the hormone of the pineal gland. This rhythm involves the transcriptional regulation of the AANAT by two norepinephrine (NE)‐inducible transcription factors, e.g. the activator pCREB (phosphorylated Ca2+/cAMP‐response element binding protein) and the inhibitor ICER (inducible cAMP early repressor). Most inbred mouse strains do not produce melatonin under standard laboratory light/dark conditions. As melatonin‐deficient mice are often the founders for transgenic animals used for chronobiological experimentations, molecular components of neuroendocrine signalling in the pineal gland as an integral part of clock entrainment mechanisms have to be deciphered. We therefore compared calcium signalling, transcriptional events and melatonin synthesis in the melatonin‐deficient C57BL mouse and the melatonin‐proficient C3H mouse. Pineal glands and primary pinealocytes were cultured and stimulated with NE or were collected at various times of the light/dark (LD) cycle. Changes in intracellular calcium concentrations, the phosphorylation of CREB, and ICER protein levels follow similar dynamics in the pineal glands of both mouse strains. pCREB levels are high during the early night and ICER protein shows elevated levels during the late night. In the C57BL pineal gland, a low but significant increase in melatonin synthesis could be observed upon NE stimulation, and, notably, also when animals were exposed to long nights. We conclude that the commonly used C57BL mouse is not completely melatonin‐deficient and that this melatonin‐deficiency does not affect molecular details involved in regulating transcriptional events of melatonin synthesis.
Tissue plasminogen activator controls multiple forms of synaptic plasticity and memory
Authors: Calabresi Paolo , Napolitano Maddalena , Centonze Diego , Marfia Girolama A. , Gubellini Paolo , Teule Martine Ammassari , Berretta Nicola , Bernardi Giorgio , Frati Luigi , Tolu Massimo , Gulino Alberto 
Published: March 2003

AbstractInduction of long‐term depression (LTD) in rat striatal slices revealed that this form of synaptic plasticity is coupled to an increased expression of tissue‐plasminogen activator (t‐PA) mRNA, as detected by the mRNA differential display technique. To further investigate the involvement of this gene in synaptic remodelling following striatal LTD, we recorded electrical activity from mice lacking the gene encoding t‐PA (t‐PA‐KO) and from wild‐type (WT) mice. Tetanic stimulation induced LTD in the large majority of striatal neurons recorded from WT mice. Conversely, LTD was absent in a significant proportion of striatal neurons obtained from mice lacking t‐PA. Electrophysiological recordings obtained from hippocampal slices in the CA1 area showed that mainly the late phase of long‐term potentiation (LTP) was reduced in t‐PA‐KO mice. Learning and memory‐related behavioural abnormalities were also found in these transgenic mice. Disruption of the t‐PA gene, in fact, altered both the context conditioning test, a hippocampus‐related behavioural task, and the two‐way active avoidance, a striatum‐dependent task. In an open field object exploration task, t‐PA‐KO mice expressed deficits in habituation and reactivity to spatial change that are consistent with an altered hippocampal function. Nevertheless, decreased rearing and poor initial object exploration were also observed, further suggesting an altered striatal function. These data indicate that t‐PA plays a critical role in the formation of various forms of synaptic plasticity and memory.
Effect of nitric oxide and NO synthase inhibition on nonquantal acetylcholine release in the rat diaphragm
Authors: Mukhtarov M. R. , Urazaev A. KH. , Nikolsky E. E. , Vyskočil F. 
Published: March 2003

AbstractAfter anticholinesterase treatment, the postsynaptic muscle membrane is depolarized by about 5 mV due to nonquantal release of acetylcholine (ACh) from the motor nerve terminal. This can be demonstrated by the hyperpolarization produced by the addition of curare (H‐effect). The magnitude of the H‐effect was decreased significantly to 3 mV when the nitric oxide (NO) donors, sodium nitroprusside (SNP) and S‐nitroso‐N‐acetylpenicillamine (SNAP) were applied to the muscle, or when NO production was elevated by addingl‐arginine, but notd‐arginine, as a substrate. The H‐effect was increased to 8–9 mV by inhibition of NO synthase byl‐nitroarginine methylester (l‐NAME), or by guanylyl cyclase inhibition by methylene blue and 1H‐[1,2,4]oxidiazolo[4,3‐a]quinoxalin‐1‐one (ODQ). ODQ increased the H‐effect to 7.3 ± 0.2 mV and diminished the SNP‐induced decrease of the H‐effect when applied together with SNP. The effects of NO donors andl‐arginine were eliminated by adding reduced haemoglobin, an extracellular NO scavenger. The present results, together with earlier evidence for the presence of NO synthase in muscle fibres, indicate that nonquantal release of ACh is modulated by NO production in the postsynaptic cell.
Glycine receptors containing the α4 subunit in the embryonic sympathetic nervous system, spinal cord and male genital ridge
Authors: Harvey Robert J. , Schmieden Volker , Von Holst Alexander , Laube Bodo , Rohrer Hermann , Betz Heinrich 
Published: March 2003

AbstractInhibitory glycine receptors (GlyRs) are known to mediate postsynaptic inhibition in spinal cord, brain stem and some higher brain regions. Several developmentally and regionally regulated GlyR isoforms exist, which result from a differential expression of the GlyR α (α1‐α4) and β subunit genes. Currently, very little is known about GlyRs containing the α4 subunit, whose existence was predicted from a partial genomic sequence. Here, we describe the isolation of complementary DNA (cDNA) sequences for the mouse and chick GlyR α4 subunits. We show that a mouse GlyR α4 subunit full‐length cDNA directs the formation of functional homo‐oligomeric strychnine‐sensitive GlyRs in Xenopus laevis oocytes and mammalian cells, and that these resemble GlyRs composed of the α1 subunit in pharmacological profile and single‐channel properties. In situ hybridization reveals high levels of GlyR α4 subunit transcripts in the embryonic (E13) chick spinal cord, lumbosacral sympathetic ganglia and dorsal root ganglia. The avian GlyR α4 subunit gene also shows male‐specific expression in the developing genital ridge. The pharmacological profile of α4 subunit‐containing receptors and deduced location of the avian GlyR α4 subunit are consistent with it being a component of the embryonic excitatory GlyRs previously identified in sympathetic neurons. Our data also suggest a novel role for GlyRs in the maturation of reproductive organs.
The retrograde inhibition of IPSCs in rat cerebellar Purkinje cells is highly sensitive to intracellular Ca2+
Authors: Glitsch Maike , Parra Paula , Llano Isabel 
Published: March 2003

AbstractThe Ca2+‐dependent retrograde inhibition of inhibitory postsynaptic currents (depolarization‐induced‐suppression of inhibition; DSI) was investigated using fura‐2 Ca2+ measurements and whole‐cell patch‐clamp recordings in rat cerebellar Purkinje cells. DSI was studied in cells loaded with different concentrations of the Ca2+ chelators BAPTA and EGTA. A concentration of 40 mm BAPTA was required to significantly interfere with DSI, whereas 10 mm BAPTA was almost ineffective. 40 mm EGTA reduced DSI, but was less effective than 40 mm BAPTA. Ratiometric Ca2+ measurements indicated that the extent of DSI depended critically on the changes in intracellular calcium ([Ca2+]i). The relationship between DSI and peak Δ[Ca2+]i could be approximated by a hyperbolic function, with apparent half‐saturation concentrations of 200 and 40 nm for dendritic and somatic [Ca2+]i, respectively. It is suggested that DSI is due to somatodendritic exocytosis of a retrograde messenger, and that this exocytosis is highly sensitive to [Ca2+]i.
Does the migraine aura reflect cortical organization?
Authors: Dahlem M. A. , Engelmann R. , Löwel S. , Müller S. C. 
Published: March 2003

AbstractIndividuals suffering from classical migraine report an astonishing diversity of migraine auras. A frequently reported symptom is a visual hallucination known as fortification illusion (FI). Here we demonstrate that the typical zig‐zag pattern of the FI can be reproduced using experimental data of orientation maps of the primary visual cortex (V1) assuming that a continuous excitation front propagates across V1. We put forward a model in which the cortical neurons within this excitation wave are activated sufficiently to contribute to conscious perception. It is shown that the discontinuous repetitive nature of the zig‐zag pattern of the FI can reflect the specific layout of visual cortical orientation maps. Additionally, dynamic features of the FI are predicted based on our model.