bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of elevated levels of nerve growth factor on the septohippocampal system in transgenic mice
Authors: Kawaja Michael D. , Walsh Gregory S. , Tovich P. Ronald , Julien Jean‐Pierre 
Published: March 2003

AbstractElevating target‐derived levels of nerve growth factor (NGF) in peripheral organs of postnatal mammals is known to enhance the survival of postganglionic sympathetic neurons and to promote the terminal arborization of sympathetic axons within such NGF‐rich target tissues. Although increasing levels of NGF in the central nervous system can ameliorate cholinergic function of damaged and aged neurons of the medial septum, it remains undetermined whether the postnatal development of this neuronal population and their projections that innervate the hippocampus are likewise affected by elevated levels of target‐derived NGF. To address this question, the cholinergic septohippocampal pathway was examined in adult transgenic mice which display elevated levels of NGF protein production in the dorsal hippocampus during postnatal development. Adult transgenic mice possessed a cholinergic population of septal neurons ≈ 15% larger than that seen in age‐matched control animals. Despite increased numbers of cholinergic septal neurons, as well as elevated levels of hippocampal NGF, the density of cholinergic septal axons in the outer molecular layer of the hippocampal dentate gyrus of adult transgenic animals was comparable with that found in wild‐type controls. These results reveal that elevating levels of target‐derived NGF during postnatal development can increase the population size of the cholinergic septal neurons but does not alter their pattern of afferent innervation in the hippocampus of adult mice.
Differential increases in chromogranins, but not synapsin I, in cortical neurons following spreading depression: implications for functional roles and transmitter peptide release
Authors: Shen Pei‐Juan , Gundlach Andrew L. 
Published: March 2003

AbstractExperimental damage of cerebral cortex induces a slow‐moving depolarization and subsequent depression of activity called cortical spreading depression (CSD) which is associated with various ionic, metabolic and genomic changes. Chromogranins are a family of water‐soluble acidic proteins with a widespread distribution in secretory, large dense‐core vesicles of neurons. We have earlier reported that secretogranin II (SgII) mRNA is increased in cerebral cortex hours after a unilateral craniotomy which would have induced CSD. To investigate further the regulation of chromogranin systems and the nature of genomic and biochemical changes produced by CSD, this study examined the temporal changes in chromogranin A (CgA), chromogranin B (CgB) and SgII mRNAs and CgB and SgII immunoreactivity (IR) in cerebral cortex and hippocampus following unilateralKCl‐induced CSD. For comparison, the levels of mRNA for synapsin I, a protein present in small synaptic vesicles was also examined. Rats were killed at various times after 10 min or 2 h of CSD and levels of chromogranins mRNAs were determined by semiquantitative in situ hybridization histochemistry, while changes in corresponding peptide products were detected by immunohistochemistry. CSD increased both SgII and CgB mRNA levels in ipsilateral cortex – levels of SgII mRNA were significantly (P < 0.01) increased at 1–6 h after CSD (165–225% of levels in contralateral cortex), but were not significantly above control values at later time points. Increased expression of CgB mRNA was delayed and prolonged compared with SgII and was significantly (P < 0.05) increased between 3 and 24 h (120–145%) after CSD, peaked at 2 days (180%), and was still elevated at 1 week (130%) compared with contralateral cortex. No alteration in CgA mRNA was observed in the ipsilateral cortex of the same animals across the entire time‐course except for an increase in piriform cortex at 1–2 days. In contrast, levels of synapsin I mRNA in affected cortex were identical to those in contralateral cortex and cortex in sham‐operated rats, at all times after CSD. Levels of chromogranin (SN‐IR and PE‐11‐IR) were also increased in ipsilateral cortex following CSD. A strong increase in SN‐IR in neuronal cell bodies and fibres was observed at 12 h and a moderate increase in PE‐11‐IR was observed 24–72 h after CSD. These results demonstrate that chromogranin transcripts and gene products are differentially regulated by neuronal depolarization/depression occurring during CSD and suggest that these chromogranin proteins may have differing functional roles in peptide transmitter release and distinct effects on neuronal function in rat brain.
Increase in syntaxin 1B and glutamate release in mossy fibre terminals following induction of LTP in the dentate gyrus: a candidate molecular mechanism underlying transsynaptic plasticity
Authors: Helme‐Guizon Alix , Davis Sabrina , Israel Maurice , Lesbats Bernard , Mallet Jacques , Laroche Serge , Hicks Andrew 
Published: March 2003

AbstractA growing body of evidence suggests that modulation of certain proteins of the exocytotic machinery is, in part, involved in the biochemical changes that underlie long‐term synaptic plasticity. We have previously shown that the induction of long‐term potentiation (LTP) at perforant path to dentate granule cell synapses in the rat hippocampus induces changes in the mRNA levels of syntaxin 1B and synapsin I, known to be involved in neurotransmitter release. Immunohistochemical staining suggested that concomitant changes in these proteins occurred at mossy fibre synapses, downstream of those synapses at which LTP was induced, leading us to postulate that such a mechanism might underlie a form of transsynaptic plasticity. Here we have used a specific mossy‐fibre synaptosome preparation to quantify levels of proteins and measure, using a chemiluminescent glutamate assay, depolarization‐induced glutamate release from these synaptosomes after induction of LTP in the dentate gyrus in vivo. We show that 5 h after the induction of LTP, there is an increase in the protein levels of syntaxin 1B and, although to a lesser extent, the synapsins I and II, associated with an increase in depolarization‐induced release of glutamate within these terminals. Increases in both the protein levels and glutamate release were not observed when dentate gyrus LTP was blocked by an NMDA receptor antagonist. From these results we propose a molecular mechanism for the propagation of synaptic plasticity through hippocampal circuits.
Piracetam facilitates long‐term memory for a passive avoidance task in chicks through a mechanism that requires a brain corticosteroid action
Authors: Loscertales María , Rose Steven P. R. , Daisley Jonathan N. , Sandi Carmen 
Published: March 2003

AbstractWe investigated the effects of piracetam, a nootropic, on learning and memory formation for a passive avoidance task in day‐old chicks. To test for the possible cognitive‐enhancing properties of piracetam, a weak learning version of this task – whereby chicks maintain a memory to avoid pecking at a bead coated in a diluted aversant for up to 10 h – was used. Post‐training (5, 30 or 60 min), but not pretraining, injections of piracetam (10 or 50 mg/kg, i.p.) increased recall for the task when the chicks were tested 24 h later. Because previous studies showed that long‐term memory for the passive avoidance task is dependent upon a brain corticosteroid action, and because the efficacy of piracetam‐like compounds is also modulated by corticosteroids, we tested whether the facilitating effect of piracetam was dependent upon a corticosteroid action through specific brain receptors (mineralocorticoid receptor and glucocorticoid receptor). First, increased plasma levels of corticosterone were found 5 min after piracetam injection. In addition, intracerebral administration of antagonists for each receptor type (RU28318, for mineralocorticoid receptors, and RU38486 for glucocorticoid receptors; i.c.) given before the nootropic inhibited the facilitative effect of piracetam on memory consolidation. These results give further support to a modulatory action of piracetam on the mechanisms involved in long‐term memory formation through a neural action that, in this learning model, requires the activation of the two types of intracellular corticosteroid receptors.
Promoter analysis of the neuronal nicotinic acetylcholine receptor α4 gene: methylation and expression of the transgene
Authors: Watanabe Hajime , Zoli Michele , Changeux Jean‐Pierre 
Published: March 2003

AbstractNeuronal nicotinic acetylcholine receptor (nAChR) subunit genes compose a family of genes. The major isoform of nAChR in the brain is made up of the α4 and β2 subunits and possesses a high affinity for nicotine. To investigate the mechanisms of the regulation of the nAChR α4 gene expression in mouse, its genomic DNA was cloned and characterized. The transcription initiation site was mapped by primer extension and RNase protection experiments and localized at about 254 bp upstream of the translation initiation site. The 5′ flanking region of this gene did not have typical TATA box but GC‐rich sequences were found around the initiation site. Methylation analysis of this region revealed that genomic DNAs from liver and muscle are partially methylated, whereas little methylation was observed in genomic DNA from brain. To characterize the cis‐acting elements driving cell‐specific expression of the α4 subunit gene, we produced lines of transgenic mice which carry a series of fragments of the α4 gene fused with bacterial lacZ as a reporter gene. An 11.5‐kb DNA fragment containing 9 kb of the region upstream of the transcription initiation site and the first intron was found to confer an expression pattern which coincides rather well with the endogenous gene expression pattern at early embryonic stages, suggesting that the elements necessary for the onset of α4 gene expression are located in this region. A DNA fragment containing the 1.8‐kb upstream sequence and the first intron drove expression of lacZ in a limited subset of α4 expressing cells, whereas the 1.8‐kb upstream sequence alone did not elicit any significant expression. These results show that both upstream and intronic sequences are important for cell‐specific expression of the nAChR α4 gene.
Regional cerebral blood flow changes in human brain related to ipsilateral and contralateral complex hand movements – a PET study
Authors: Kawashima Ryuta , Matsumura Michikazu , Sadato Norihiro , Naito Eichi , Waki Atsuo , Nakamura Satoshi , Matsunami Kenichi , Fukuda Hiroshi , Yonekura Yoshiharu 
Published: March 2003

AbstractThe purpose of this study was to investigate the cortical motor areas activated in relation to unilateral complex hand movements of either hand, and the motor area related to motor skill learning. Regional cerebral blood flow (rCBF) was measured in eight right‐handed healthy male volunteers using positron emission tomography during a two‐ball‐rotation task using the right hand, the same task using the left hand and two control tasks. In the two‐ball‐rotation tasks, subjects were required to rotate the same two iron balls either with the right or left hand. In the control task, they were required to hold two balls in each hand without movement. The primary motor area, premotor area and cerebellum were activated bilaterally with each unilateral hand movement. In contrast, the supplementary motor area proper was activated only by contralateral hand movements. In addition, we found a positive correlation between the rCBF to the premotor area and the degree of improvement in skill during motor task training. The results indicate that complex hand movements are organized bilaterally in the primary motor areas, premotor areas and cerebellum, that functional asymmetry in the motor cortices is not evident during complex finger movements, and that the premotor area may play an important role in motor skill learning.
Importance of neurokinin‐1 receptors in the nucleus tractus solitarii of mice for the integration of cardiac vagal inputs
Authors: Paton Julian F. R. 
Published: March 2003

AbstractUnmyelinated vagal afferents from the heart terminate within the nucleus tractus solitarii (NTS) located in the dorsomedial medulla. The neurotransmitter and postsynaptic receptors mediating information from cardiac vagal receptors to the NTS are unknown. This study determined the effects of neurokinin‐1 (NK1) receptor blockade on: (i) the reflex response evoked following aortic root injection of either veratridine (1–3 μg/kg) or bradykinin (80–300 ng/kg) to stimulate cardiac receptors in in vivo anaesthetized mice; and (ii) the evoked synaptic response of cardioreceptive NTS neurons following both intraleft‐ventricular injection of veratridine or bradykinin, and electrical stimulation of the ipsilateral vagus nerve in an arterially perfused working heart‐brainstem preparation of mouse. Administration of CP‐99,994 (0.75–1.5 mg/kg i.v.), a specific NK1 antagonist, attenuated significantly the evoked reflex bradycardia and depressor response following cardiac receptor (n = 6), but not pulmonary chemoreflex stimulation in vivo. From extracellular recordings of cardioreceptive NTS neurons, CP‐99,994 reduced reversibly the total number of evoked spikes, peak firing frequency and response duration evoked by intraventricular injections of veratridine (n = 5) or bradykinin (n = 5). The number of evoked action potentials following electrical stimulation of the vagus nerve was also reduced. In five whole cell recordings of NTS neurons, both the evoked depolarization following cardiac receptor stimulation, and the peak amplitude and duration of vagus nerve‐evoked EPSPs were reduced by CP‐99 994; synaptic inputs from both peripheral chemoreceptors or pulmonary C‐fibres were unaffected. These data support a selective involvement of NK1 receptors in the transmission of cardiac vagal afferent inputs to NTS neurons integrating cardiorespiratory information.
Neuronal survival and calcium influx induced by basic fibroblast growth factor in chick ciliary ganglion neurons
Authors: Distasi Carla , Torre Marina , Antoniotti Susanna , Munaron Luca , Lovisolo Davide 
Published: March 2003

AbstractBasic fibroblast growth factor (bFGF/FGF2) exhibits widespread biological activities in the nervous system. However, little is known about the cascade of intracellular events that links the activation of its tyrosine kinase receptors to these effects. Here we report that, in ciliary ganglion neurons from chick embryo, this trophic factor significantly enhanced neuronal survival. The percentage of surviving neurons was reduced when intracellular calcium was chelated by adding a membrane‐permeable BAPTA ester to the culture medium, while antagonists of L‐ and N‐type voltage‐dependent calcium channels were ineffective. The ionic signals in response to bFGF stimulation have been studied using cytofluorimetric and patch‐clamp techniques. In single‐cell Fura‐2 measurements, bFGF elicited a long lasting rise of the cytosolic calcium concentration that was dependent on [Ca2+]o. In whole‐cell experiments, we observed a reversible depolarization of the membrane resting potential and an inward cationic current. Single channel experiments, performed in the cell‐attached configuration, provide evidence for the activation of two families of Ca2+‐permeable cationic channels. Moreover, inositol 1,4,5‐trisphosphate opens channels with similar properties, suggesting that this cytosolic messenger can be responsible for the calcium influx induced by bFGF.
Postnatal expression of H1‐receptor mRNA in the rat brain: correlation to l‐histidine decarboxylase expression and local upregulation in limbic seizures
Authors: Lintunen Minnamaija , Sallmen Tina , Karlstedt Kaj , Fukui Hiroyuki , Eriksson Krister S. , Panula Pertti 
Published: March 2003

AbstractHistamine is implicated in the regulation of brain functions through three distinct receptors. Endogenous histamine in the brain is derived from mast cells and neurons, but the importance of these two pools during early postnatal development is still unknown. The expression of histamine H1‐receptor in the rat brain was examined using in situ hybridization during postnatal development and in adults. For comparison, the expression of l‐histidine decarboxylase (HDC) in the two pools was revealed. H1‐receptor was evenly expressed throughout the brain on the first postnatal days, but resembled the adult, uneven pattern already on postnatal day 5 (P5). HDC was expressed in both mast cells and tuberomammillary neurons from birth until P5, after which the mast cell expression was no more detectable. In adult rat brain, high or moderate levels of H1‐receptor expression were found in the hippocampus, zona incerta, medial amygdaloid nucleus and reticular thalamic nucleus. In most areas of the adult brain the expression of H1‐receptor mRNA correlates well with binding data and histaminergic innervation. A notable exception is the hypothalamus, with high fibre density but moderate or low H1‐receptor expression. Systemic kainic acid administration induced increased expression of H1‐receptor mRNA in the caudate‐putamen and dentate gyrus, whereas no change was seen in the hippocampal subfields CA1–CA3 or in the entorhinal cortex 6 h after kainic acid injections. This significant increase supports the concept that histaminergic transmission, through H1‐receptor, is involved in the regulation of seizure activity in the brain.
A peptide activator of endogenous tyrosine kinase enhances synaptic currents mediated by NMDA receptors
Authors: Lancaster B. , Rogers M. V. 
Published: March 2003

AbstractN‐methyl‐d‐aspartic acid (NMDA) receptor currents in cultured cells or expression systems are increased by the addition of purified tyrosine kinases. However, there is no direct demonstration of this effect at NMDA receptors in intact synapses of rat brain slices. Transmitters which might be used to activate tyrosine kinases in situ are unlikely to have a sufficiently selective action to allow a clear interpretation of their effects. Therefore, we used a phosphotyrosine‐containing decapeptide which can be included in recording electrodes to activate postsynaptic src‐family tyrosine kinases. This peptide enhanced NMDA responses in dissociated hippocampal CA1 neurons. These effects were not reproduced by a non‐phosphorylated peptide or a scrambled‐sequence phosphopeptide. The enhancement of NMDA responses was blocked by a tyrosine kinase inhibitor. In brain slices the phosphopeptide, but not control peptide, increased NMDA receptor‐mediated synaptic current indicating that endogenous tyrosine kinase can upregulate the response of NMDA receptors at glutamatergic synapses in the hippocampus.
The voltage‐dependent conductances of rat neocortical layer I neurons
Authors: Budde Thomas , White John A. 
Published: March 2003

AbstractWhole cell patch‐clamp techniques were used to study voltage‐dependent sodium (Na+), calcium (Ca2+), and potassium (K+) conductances in acutely isolated neurons from cortical layer I of adult rats. Layer I cells were identified by means of γ‐aminobutyric acid (GABA) immunocytochemistry. Positive stainings for the Ca2+‐binding protein calretinin in a subset of cells, indicated the presence of Cajal–Retzius (C‐R) cells. All investigated cells displayed a rather homogeneous profile of voltage‐dependent membrane currents. A fast Na+ current activated at about −45 mV, was half‐maximal steady‐state inactivated at −66.6 mV, and recovery from inactivation followed a two‐exponential process (τ1 = 8.4 ms and τ2 = 858.8 ms). Na+ currents declined rapidly with two voltage‐dependent time constants, reaching baseline current after some tens of milliseconds. In a subset of cells (< 50%) a constant current level of < 65 pA remained at the end of a 90 ms step. A transient outward current (Ifast) activated ≈–40 mV, declined rapidly with a voltage‐insensitive time constant (τ≈ 350 ms) and was relatively insensitive to tetraethylammonium (TEA, 20 mm). Ifast was separated into two components based on their sensitivity to 4‐aminopyridine (4‐AP): one was blocked by low concentrations (40 μm) and a second by high concentrations (6 mm). After elimination of Ifast by a conditioning prepulse (50 ms to −50 mV), a slow K+ current (IKV) could be studied in isolation. IKV was only moderately affected by 4‐AP (6 mm), while TEA (20 mm) blocked most (> 80%) of the current. IKV activated at about −40 mV, declined monoexponentially in a voltage‐dependent manner (τ≈ 850 ms at −30 mV), and revealed an incomplete steady‐state inactivation. In addition to Ifast and IKV, indications of a Ca2+‐dependent outward current component were found. When Na+ currents, Ifast, and IKV were blocked by tetrodotoxin (TTX, 1 μm), 4‐AP (6 mm) and TEA (20 mm) an inward current carried by Ca2+ was found. Ca2+ currents activated at depolarized potentials at about −30 mV, were completely blocked by 50 μm cadmium (Cd2+), were sensitive to verapamil (≈ 40% block by 10 μm), and were not affected by nickel (50 μm). During current clamp recordings, isolated layer I neurons displayed fast spiking behaviour with short action potentials (≈ 2 ms, measured at half maximal amplitude) of relative small amplitude (≈ 83 mV, measured from the action potential threshold).
Modulation of big K+ channel activity by ryanodine receptors and L‐type Ca2+ channels in neurons
Authors: Chavis Pascale , Ango Fabrice , Michel Jean‐Marie , Bockaert Joel , Fagni Laurent 
Published: March 2003

AbstractAs metabotropic glutamate receptor type 1 (mGluR1) is known to couple L‐type Ca2+ channels and ryanodine receptors (RyR, Chavis et al. 1996) in cerebellar granule cells, we examined if such a coupling could activate a Ca2+‐sensitive K+ channel, the big K+ (BK) channel, in cultured cerebellar granule cells. We observed that (±)‐1‐amino‐cyclopentane‐trans‐1,3‐dicarboxylic acid (t‐ACPD) and quisqualate (QA) stimulated the activity of BK channels. On the other hand, (2S, 3S, 4S)‐α‐carboxycyclopropyl‐glycine (L‐CCG‐I) and l‐(+)‐2‐amino‐4‐phosphonobutyrate (L‐AP4) had no effect on BK channels, indicating a specific activation by group I mGluRs. Group I mGluRs stimulation of the basal BK channel activity was mimicked by caffeine and both effects were blocked by ryanodine and nifedipine. Interestingly, carbachol stimulated BK channel activity but through a pertussis toxin (PTX)‐sensitive pathway that was independent of L‐type Ca2+ channel activity. Our report indicates that unlike the muscarinic receptors, group I mGluRs activate BK channels by mobilizing an additional pathway involving RyR and L‐type Ca2+ channels.