bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discrete localizations of hedgehog signalling components in the developing and adult rat nervous system
Authors: Traiffort Elisabeth , Charytoniuk Dorota , Watroba Laurent , Faure Hélène , Sales Nicole , Ruat Martial 
Published: March 2003

AbstractSonic hedgehog (Shh), a morphogen molecule implicated in embryonic tissue patterning, displays inductive, proliferative, neurotrophic and neuroprotective activities on various neural cells. Shh might exert its biological functions through binding to patched (Ptc) associated with smoothened (Smo), leading to downstream activation of target genes such as the transcription factor Gli1. We have performed a detailed localization of cells expressing transcripts of Shh, Ptc, Smo and Gli1 in brain and spinal cord of the adult rat as well as in the developing cerebellum. In the adult, Shh‐positive cells were mainly observed in forebrain structures, in the Purkinje cells of the cerebellum and in motor neurons. Ptc‐positive cells were frequently observed in brain areas devoid of any Shh transcripts, except in the median eminence or the facial nucleus, suggesting local Shh signalling. Interestingly, Smo transcripts were predominantly present within circumventricular organs, in granular cells of the dentate gyrus and in neurons of the reticular thalamic nucleus. The presence of Shh, Ptc and Smo transcripts in hypothalamic areas may indicate a role of Shh signalling in the modulation of neuroendocrine functions. The expression pattern of these three genes as well as of Gli1, and their developmental regulation in the cerebellum, suggest a possible role for Hedgehog signalling in the control of various cell populations within the cerebellum, particularly in granule cell proliferation and/or differentiation that might be impaired in proliferative states such as medulloblastomas.
Redistribution of presynaptic proteins during α‐latrotoxin‐induced release of neurotransmitter and membrane retrieval at the frog neuromuscular junction
Authors: Boudier Jeanne‐Andrée , Martin‐Moutot Nicole , Boudier Jean‐Louis , Iborra Cecile , Takahashi Masami , Seagar Michael J. 
Published: March 2003

AbstractCalcium‐dependent exocytosis at the nerve terminal involves the synaptic core (SNARE) complex composed of the t‐SNAREs syntaxin 1 and synaptosome‐associated protein of 25 kDa (SNAP‐25), and the v‐SNARE vesicle‐associated membrane protein (VAMP/synaptobrevin), a stable heterotrimer which can associate with the putative calcium sensor protein, synaptotagmin. The distribution of these proteins at the frog neuromuscular junction was examined by immunofluorescent staining and confocal microscopy following exocytosis induced by α‐latrotoxin. Experiments were performed under conditions in which synaptic vesicle recycling was either maintained in balance with exocytosis, or completely blocked, or during recovery from block of endocytosis. When endocytosis was maintained, protein distribution was essentially identical to that of unstimulated nerve terminals, in which syntaxin 1 and SNAP‐25 are localized to the presynaptic active zones coincident with the postsynaptic folds that contain a high density of acetylcholine receptors (AChRs). Block of endocytosis led to complete incorporation of vesicle proteins into the plasmalemma, and t‐SNARE distribution was no longer restricted to active zones. Five minutes after the onset of recovery, both synaptic vesicle proteins and t‐SNARE proteins were concentrated into small spots, in a similar pattern to that obtained following endocytosis of the vital styryl dye FM1‐43. These findings are consistent with a model in which following sustained exocytosis, t‐SNARE trafficking involves internalization and transit via a vesicular compartment before recycling to the presynaptic plasma membrane.
Acetylcholine suppresses the spread of excitation in the visual cortex revealed by optical recording: possible differential effect depending on the source of input
Authors: Kimura Fumitaka , Fukuda Mitsuhiro , Tsumoto Tadaharu 
Published: March 2003

AbstractOptical recording with a voltage‐sensitive dye was performed in visual cortical slices of the rat to determine the effect of acetylcholine (ACh) on the spread of excitation. In the presence of ACh, the spread of excitation initiated by stimulation at the white matter/layer VI (WM/VI) was greatly suppressed throughout the cortex, with less suppression in the middle layers. By comparing the effect of ACh with that of 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX), the fraction of the synaptic component that was sensitive to ACh was evaluated. ACh suppressed ∼ 40–50% (maximum 55.8%, n = 11) of the initial synaptic component in the superficial and deep layers. In the middle, however, the effect was weakest and only ∼ 20–30% (minimum 20.9%, n = 11) of the initial synaptic component was suppressed. On the basis of histological analysis, the region with the weakest ACh effect extended from upper V to lower II/III. To identify the site of ACh action in terms of pre‐ versus postsynaptic localization, exogenous glutamate was applied. Because ACh did not suppress the excitation induced by glutamate, the site of the ACh action was indicated to be presynaptic. When layer II/III was stimulated instead of WM/VI, the suppression was uniform throughout the cortex. A muscarinic receptor antagonist, atropine, blocked the suppression by ACh. In conclusion, our results indicate the following two points. First, ACh strongly suppresses intracortical connectivity through presynaptic muscarinic receptors. Secondly, in contrast to the intracortical connection, some group(s) of fibres, possibly thalamocortical afferents that arise from white matter and terminate in the middle cortical layers are suppressed much less by ACh. While ACh has been reported to have confusingly diverse effects, e.g. direct depolarization and hyperpolarization as well as synaptic facilitation and suppression, its effect on the propagation of excitation is very clear; suppression on intracortical connection, leaving thalamocortical inputs rather intact. We postulate that cholinergic innervation enables the afferent input to have a relatively dominant effect in the cortex.
Functional NMDA and GABAA receptors in pioneer neurons of the cortical marginal zone
Authors: Soria José Miguel , Martínez‐Galán Juan Ramón , Luján Rafael , Valdeolmillos Miguel , Fairén Alfonso 
Published: March 2003

AbstractTransient pioneer neurons in the neocortical marginal zone generate an early corticofugal axonal projection at E12–E16 (Meyer et al. 1998). We have analysed the functional activity of glutamate and GABA receptors in such cells by measuring changes in intracellular calcium concentrations ([Ca2+]i). The activation of GABAA receptors with muscimol, as well as bath application of glutamate, lead to increases in [Ca2+]i in pioneer neurons. The stimulatory action of glutamate is mostly produced through the NMDA‐type of ionotropic receptors. Metabotropic glutamate receptor activation has no effect on [Ca2+]i. Consistent with such results, immunocytochemical studies showed a prominent expression of GABAA and NMDA receptors in pioneer neurons. The activation of such receptors may be implicated in the remodelling of pioneer neurons during development.
Endogenous adenosine protects CA1 neurons from kainic acid‐induced neuronal cell loss in the rat hippocampus
Authors: Matsuoka Yasuji , Okazaki Mitsuhiro , Takata Kazuyuki , Kitamura Yoshihisa , Ohta Shyunsaku , Sekino Yuko , Taniguchi Takashi 
Published: March 2003

AbstractCA3 pyramidal neurons in the rat hippocampus show selective vulnerability to the intracerebroventricular injection of kainic acid (KA). However, the mechanism of this selective neuronal vulnerability remains unclear. In this study, we examined the contribution of endogenous adenosine, a potent inhibitory neuromodulator, to the differences in the neuronal vulnerability of the hippocampus, using microtubule‐associated protein (MAP)‐2, phosphorylated c‐Jun, and major histocompatibility complex (MHC) class II immunoreactivities as markers for neuronal cell loss, neuronal apoptosis and glial activation, respectively. Pretreatment with 8‐cyclopenthyltheophylline (CPT), an A1 adenosine receptor antagonist, significantly exacerbated KA‐induced neuronal cell loss in both the CA1 and CA3. Although c‐Jun phosphorylation, a critical step in neuronal apoptosis, was not detected in the vehicle‐injected rat hippocampus, c‐Jun phosphorylation was induced in the CA3 by the injection of KA alone. Pretreatment with CPT induced c‐Jun phosphorylation in both the CA1 and CA3. MHC class II antigen was also detected in the regions of c‐Jun phosphorylation. Coadministration of N6‐cyclopenthyladenosine (CHA), an A1 adenosine receptor agonist, attenuated the neuronal cell loss in the CA1 and CA3 with or without pretreatment with CPT. These results strongly suggest that endogenous adenosine has neuroprotective effects against excitotoxin‐induced neurodegeneration in the CA1 through its A1 receptors.
Previous maternal experience potentiates the effect of parturition on oxytocin receptor mRNA expression in the paraventricular nucleus
Authors: Broad K. D. , Lévy F. , Evans G. , Kimura T. , Keverne E. B. , Kendrick K. M. 
Published: March 2003

AbstractIn sheep, central oxytocin release at parturition induces maternal behaviour which is thought to be mediated by changes in the expression of central oxytocin receptors. The distribution, effects of parturition, previous maternal experience and hormonal status on the distribution of an oxytocin receptor was investigated using immunocytochemistry and in situ hybridization. In ewes with no previous maternal experience, parturition induced significant increases in oxytocin receptor mRNA expression in the anterior olfactory nucleus, medial preoptic area, ventromedial hypothalamus, lateral septum, medial amygdala, bed nucleus of the stria terminalis and diagonal band of Broca. In maternally experienced ewes, parturition induced additional increases in two areas, the paraventricular nucleus and the Islands of Calleja. The changes in progesterone and oestrogen that occur during late pregnancy and parturition appear to contribute to increases in expression in the anterior olfactory nucleus, Islands of Calleja, medial preoptic area, ventromedial hypothalamus, bed nucleus of the stria terminalis and diagonal band of Broca, but not in the paraventricular nucleus, lateral septum and medial amygdala. These results demonstrate that progesterone and oestrogen priming enhance oxytocin receptor mRNA expression in a number of regions in the olfactory system, hypothalamus and limbic brain. These effects appear to be independent of maternal experience. Parturition increases oxytocin receptor mRNA expression in all the areas influenced by hormonal priming and the lateral septum, medial amygdala and paraventricular nucleus. Maternal experience also enhances expression of oxytocin receptor mRNA in the paraventricular nucleus and the Islands of Calleja. Because the paraventricular nucleus is the main source of oxytocin release in the brain, this upgrading of autoreceptors as a result of maternal experience may serve to enhance release of this peptide in projection sites regulating maternal behaviour.
Functional circuitry for the induction of prolonged excitation in the rat spinal dorsal horn
Authors: Murase Kazuyuki , Saka Takashi , Asai Tatsuya , Ikeda Hiroshi 
Published: March 2003

AbstractThe neuronal circuitry through which prolonged excitation is generated in the spinal dorsal horn was investigated using optical imaging of neuronal excitation in transverse slices of rat spinal cords. It is known that tetanic stimulation (20 Hz for 1 s) of the dorsal root that activates both A and C primary afferent fibres elicits slow intrinsic optical signals (IOS) in the dorsal horn, seen most intensely in the substantia gelatinosa (SG), lamina II, and that IOS expresses in part the slow synaptic response recorded intracellularly in dorsal horn neurons. We here report that the slow IOS within the SG were completely abolished after an incision was made at the border between the SG and the deeper laminae, but not after an incision within the deeper dorsal horn of the laminae III–V. The result demonstrates directly that, in order to generate prolonged excitation in the SG, the neuronal elements in the deeper dorsal horn must be intact. Thus, the afferent information might be received first by the deeper elements and then transmitted to the SG region, and/or collaboration between the SG and deeper elements is necessary to maintain prolonged excitation in the SG.
Regional brain activity during shape recognition impaired by a scopolamine challenge to encoding
Authors: Rosier Anne‐Marie , Cornette Luc , Dupont Patrick , Bormans Guy , Mortelmans Luc , Orban Guy A. 
Published: March 2003

AbstractIn the present positron emission tomography (PET) study, we examine the effect of a scopolamine‐induced challenge to encoding upon the pattern of regional cerebral blood flow during recognition of a list of abstract visual shapes 3 days after encoding of these shapes. This study was conducted to test hypotheses concerning the fusiform and thalamic contributions to object recognition arising from a previous imaging study of impaired recognition. In that study, we demonstrated that activity in the fusiform cortex and the thalamus during shape recognition was modulated by memory challenges. These memory challenges included, on one hand, impaired storage as a consequence of diazepam administration during encoding, and, on the other hand, impaired retrieval caused by a perceptual challenge. Activation in the fusiform cortex decreased during impaired recognition, irrespective of the type of challenge. In contrast, thalamic activation increased only when the recognition deficit resulted from impaired memory storage. Based on these results, we hypothesized that fusiform activation during recognition reflects the matching of an incoming stimulus with a stored one, whereas thalamic activation reflects retrieval attempts. These hypotheses would receive considerable support if scopolamine, which also impairs memory storage, induced similar modulations of fusiform and thalamic activation. In the present study, we observed that a scopolamine challenge to encoding does indeed modulate the activity in the very same regions that were previously modulated by a diazepam challenge. Hence, a similar memory deficit, although primarily effected through different neurochemical pathways, was paralleled by a similar modulation of activity in the same set of nodes in the shape recognition network. In the fusiform cortex, scopolamine decreased recognition‐related activity, as did the sensory challenge of retrieval. Furthermore, covariate analysis demonstrated that the level of fusiform activity linearly correlates with behavioural performance. In the thalamus, activation increased following impaired encoding. This is in accordance with the idea that enhanced thalamic activity reflects increased effort expended in retrieval. In addition, in the intraparietal sulcus, differential activation also increased following impaired memory storage, possibly reflecting enhanced visuospatial attention in an effort to compensate for impaired performance.
Carbachol‐induced changes in excitability and [Ca2+]i signalling in projection cells of medial entorhinal cortex layers II and III
Authors: Gloveli Tengis , Egorov Alexei V. , Schmitz Dietmar , Heinemann Uwe , Müller Wolfgang 
Published: March 2003

AbstractThe entorhinal cortex (EC) is a major gateway for sensory information into the hippocampus and receives a cholinergic input from the forebrain. Therefore, we studied muscarinic effects on excitability and intracellular Ca2+ signalling in layer II stellate and layer III pyramidal projection neurons of the EC. In both classes of neurons, local pressure‐pulse application of carbachol (1 mm) caused small, atropine‐sensitive membrane depolarizations that were not accompanied by any detectable changes in [Ca2+]i. At a higher concentration (10 mm), carbachol induced a larger membrane depolarization associated with synaptic oscillations and epileptiform activity in both classes of neurons. In contrast to the intrinsic theta rhythm in stellate cells with one dominant peak frequency at ∼ 7 Hz, the synaptically mediated oscillation induced by carbachol showed three characteristic peaks in the theta and gamma frequency range at ∼ 11, 23 and 40 Hz. Although carbachol‐induced epileptiform activity was associated with increases in intracellular free Ca2+ in both layer II and III cells, the observed [Ca2+]i accumulation was significantly larger in layer III than in layer II cells. Responses to intracellular current injections showed differences in Ca2+ accumulation in layer II and III cells at the same membrane potentials, suggesting a dominant expression of low‐ and high‐voltage‐activated Ca2+ channels in these layer II and III cells, respectively. In conclusion, we present evidence for significant differences in the [Ca2+]i regulation between layer II stellate and layer III pyramidal cells of the medial EC.
1‐Aminoindan‐1,5‐dicarboxylic acid and (S)‐(+)‐2‐(3′‐carboxybicyclo[1.1.1] pentyl)‐glycine, two mGlu1 receptor‐preferring antagonists, reduce neuronal death in in vitro and in vivo models of cerebral ischaemia
Authors: Pellegrini‐Giampietro Domenico E. , Cozzi Andrea , Peruginelli Fiamma , Leonardi Patrizia , Meli Elena , Pellicciari Roberto , Moroni Flavio 
Published: March 2003

AbstractMetabotropic glutamate (mGlu) receptors have been implicated in a number of physiological and pathological responses to glutamate, but the exact role of group I mGlu receptors in causing postischaemic injury is not yet clear. In this study, we examined whether the recently‐characterized and relatively selective mGlu1 receptor antagonists 1‐aminoindan‐1,5‐dicarboxylic acid (AIDA) and (S)‐(+)‐2‐(3′‐carboxybicyclo[1.1.1]pentyl)‐glycine (CBPG) could reduce neuronal death in vitro, following oxygen‐glucose deprivation (OGD) in murine cortical cell and rat organotypic hippocampal cultures, and in vivo, after global ischaemia in gerbils. When present in the incubation medium during the OGD insult and the subsequent 24 h recovery period, AIDA and CBPG significantly reduced neuronal death in vitro. The extent of protection was similar to that observed with the nonselective mGlu receptor antagonist (+)‐α‐methyl‐4‐carboxyphenylglycine [(+)MCPG] and with typical ionotropic glutamate (iGlu) receptor antagonists. Neuroprotection was also observed when AIDA or CBPG were added only after the OGD insult was terminated. Neuronal injury was not attenuated by the inactive isomer (–)MCPG, but was significantly enhanced by the nonselective mGlu receptor agonist (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid [(1S,3R)‐ACPD] and the group I mGlu receptor agonist 3,5‐dihydroxyphenylglycine (3,5‐DHPG). The antagonists (+)MCPG, AIDA and CBPG were also neuroprotective in vivo, because i.c.v. administration reduced CA1 pyramidal cell degeneration examined 7 days following transient carotid occlusion in gerbils. Our results point to a role of mGlu1 receptors in the pathological mechanisms responsible for postischaemic neuronal death and propose a new target for neuroprotection.
Angiotensin II receptor subtype gene expression and cellular localization in the retina and non‐neuronal ocular tissues of the rat
Authors: Wheeler‐Schilling Thomas H. , Kohler Konrad , Sautter Monika , Guenther Elke 
Published: March 2003

AbstractIn addition to its function as a peripheral hormone, angiotensin II (AngII) has been shown to act as a neuromodulator in various brain regions. AngII effects are mediated by two major AngII receptor subtypes, AT1 and AT2, and different AT1 receptor isoforms AT1A and AT1B are described in rat brains. The purpose of the present study was to analyse the expression pattern of AT receptors in different parts of the rat eye with special emphasis on the retina. Specific primers were constructed and the gene expression of AngII receptor subtypes was investigated by means of reverse transcription‐polymerase chain reaction (RT‐PCR). An antibody was used for cellular localization of AT1 receptor in the retina. AT2 receptor mRNA was localized by in situ hybridization (ISH). We examined the retinas of different developmental stages as well as non‐neuronal ocular tissues, e.g. choroid and anterior uveal tract of rats (Brown Norway and Wistar strain), for the gene expression of AT receptors. Our results show that AT1A and AT2 mRNAs are expressed in rat choroid, iris/ciliary body and retinas, whereas AT1B mRNA is not expressed in the retina but in all other ocular tissues under investigation. AT1 receptor immunohistochemistry of the retina showed strong labelling in the ganglion cell layer (GCL), and some cells in the inner nuclear layer (INL), suggesting putative ganglion cell but also amacrine cell labelling. In the retina, ISH for AT2 mRNA revealed labelling in the GCL and a faint labelling in the inner nuclear layer. No AT2 ISH‐signal was found in the other ocular tissues. These data suggest that there is a specific distribution pattern of AT receptors in rat ocular tissues, especially in the retina. The expression of AT receptors on retinal ganglion cells confirms the AngII action on these cell types and supports the role of AngII as a retinal neurotransmitter or neuromodulator.
Cortical and nigral deafferentation and striatal cholinergic markers in the rat dorsal striatum: different effects on the expression of mRNAs encoding choline acetyltransferase and muscarinic m1 and m4 receptors
Authors: Kayadjanian N. , Schofield W. N. , Andren J. , Sirinathsinghji D. J. S. , Besson M. ‐J. 
Published: March 2003

AbstractThe regulation of the striatal m1 and m4 muscarinic receptor mRNA as well as the choline acetyltransferase (ChAT) mRNA expression by nigral dopaminergic and cortical glutamatergic afferent fibres was investigated using quantitative in situ hybridization histochemistry. The effects induced by a unilateral lesion of the medial forebrain bundle and a bilateral lesion of the sensorimotor (SM) cortex were analysed in the dorsal striatum 3 weeks after the lesions. Dopaminergic denervation of the striatum resulted in a marked decrease in the levels of m4 mRNA throughout the striatum, while the levels of muscarinic m1 mRNA and ChAT mRNA in cholinergic neurons were unaffected by the lesion. In contrast, following bilateral cortical ablation, the levels of the muscarinic m1 mRNA were significantly increased in the striatal projection area of the SM cortex, whereas the expression of m4 mRNA remained unchanged. Single cholinergic cell analysis by computer‐assisted grain counting revealed a decreased labelling for ChAT mRNA per neuron following cortical ablation. However, in contrast to the topographical m1 mRNA changes, the decreased ChAT mRNA expression was evenly distributed within the striatum, suggesting an indirect cortical control upon striatal cholinergic interneurons. Altogether, these data suggest that dopaminergic nigral and glutamatergic cortical afferents modulate differentially cholinergic markers, at the pre‐ and post‐synaptic levels. Beside the fact that nigral and cortical inputs exert an opposite control on cholinergic neurotransmission, our study further shows that this control involved different muscarinic receptor subtypes: the m4 and m1 receptors, respectively.