bluuebunny/crossref_metadata_2025_split huggingface dataset:
Target Selectivity and Neurochemical Characteristics of VIP‐immunoreactive Interneurons in the Rat Dentate Gyrus
Authors: Hájos Norbert , Acsády László , Freund Tamás F. 
Published: April 2006

AbstractVasoactive intestinal polypeptide (VIP) has been shown to be present in a morphologically heterogeneous subpopulation of interneurons in the dentate gyrus, but the relationship between their input and output characteristics and neurochemical features has not been established. Three types of VIP‐immunoreactive cells have been identified on the basis of these criteria: (i) cells forming a dense axonal plexus in the hilus have always coexisted with the calcium binding protein calretinin (CR), but never with the neuropeptide cholecystokinin (CCK). The postsynaptic targets of these VIP‐positive cells were neurons visualized by immunostaining for substance P receptor, which is known to label different hilar non‐principal cells. (ii) VIP‐immunoreactive basket cells, innervating predominantly the somata and proximal dendrites of granule cells, were found in the stratum moleculare and stratum granulosum. They contained CCK, but not CR. (iii) Cells projecting to the stratum moleculare were found to have dendrites and axons restricted to this layer. In 75% of these cells VIP coexisted with CR but not with CCK, and they established multiple contacts largely with non‐principal cells. GABA was shown to be present but the calcium‐binding proteins calbindin D28K and parvalbumin were absent in all three types of VIP‐containing interneuron. On the basis of these observations we conclude that three different types of VIP‐positive neuron are present in this area, and are likely to subserve different inhibitory functions: cells with a hilar projection as well as those projecting to the stratum moleculare may synchronize the activity of hilar and other interneurons, or disinhibit granule cells by specific interneuron‐to‐interneuron connections. In contrast, basket cells control the activity of granule cells directly, via perisomatic inhibition.
Autocrine—paracrine Regulation of Hippocampal Neuron Survival by IGF‐1 and the Neurotrophins BDNF, NT‐3 and NT‐4
Authors: Lindholm Dan , Carroll Patrick , Tzimagiorgis Georgios , Thoenen Hans 
Published: April 2006

AbstractIn contrast to sympathetic and sensory neurons in the peripheral nervous system, the neurotrophic requirements for neurons in the central nervous system (CNS) have not been clearly identified. The inactivation of specific neurotrophic factors and their receptors by gene targeting has shown that there are no major changes in neuron numbers in the CNS. This suggests an overlap between the action of different neurotrophic factors in the brain during development. Here we have studied the survival of hippocampal neurons prepared from embryonic rats, using different culture conditions. Whereas the hippocampal neurons survive well in culture when plated at high density, they die at lower cell densities in the absence of appropriate neurotrophic factors. Under the latter conditions, both insulin‐like growth factor‐1 (IGF‐1) and the neurotrophins—brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3) and neurotrophin‐4 (NT‐4)—rescued a large proportion of cultured neurons. In addition, hippocampal neurons from BDNF knockout mice exhibited enhanced cell death compared with cells from wild‐type animals. BDNF and IGF‐1 both increased the survival of the hippocampal neurons lacking BDNF, showing complementary action for these factors in supporting survival. Blocking antibodies against NT‐3 and IGF‐1 decreased hippocampal neuron survival at low cell densities, showing autocrine or paracrine action of the factors. At higher cell densities, however, the antibodies had no effect, demonstrating that there is a sufficient amount of endogenous factors supporting survival under these conditions. The present results show that hippocampal neurons depend for survival on local neurotrophic factors such as IGF‐1, BDNF and NT‐3, which act in an autocrine/paracrine manner. The multifactorial support of hippocampal neurons ensures a maximal degree of neuron survival even in the absence of an individual factor.
Perisynaptic Location of Metabotropic Glutamate Receptors mGluR1 and mGluR5 on Dendrites and Dendritic Spines in the Rat Hippocampus
Authors: Luján Rafael , Nusser Zoltan , Roberts J. David B. , Shigemoto Ryuichi , Somogyi Peter 
Published: April 2006

AbstractIonotropic and metabotropic (mGluR1a) glutamate receptors were reported to be segregated from each other within the postsynaptic membrane at individual synapses. In order to establish whether this pattern of distribution applies to the hippocampal principal cells and to other postsynaptic metabotropic glutamate receptors, the mGluR1a/b/c and mGluR5 subtypes were localized by immunocytochemistry. Principal cells in all hippocampal fields were reactive for mGluR5, the strata oriens and radiatum of the CA1 area being most strongly immunolabelled. Labelling for mGluR1b/c was strongest on some pyramids in the CA3 area, weaker on granule cells and absent on CA1 pyramids. Subpopulations of non‐principal cells showed strong mGluR1 or mGluR5 immunoreactivity. Electron microscopic pre‐embedding immunoperoxidase and both pre‐ and postembedding immunogold methods consistently revealed the extrasynaptic location of both mGluRs in the somatic and dendritic membrane of pyramidal and granule cells. The density of immunolabelling was highest on dendritic spines. At synapses, immunoparticles for both mGluR1 and mGluR5 were found always outside the postsynaptic membrane specializations. Receptors were particularly concentrated in a perisynaptic annulus around type I synaptic junctions, including the invaginations at ‘perforated’synapses. Measurements of immunolabelling on dendritic spines showed decreasing levels of receptor as a function of distance from the edge of the synaptic specialization. We propose that glutamatergic synapses with an irregular edge develop in order to increase the circumference of synaptic junctions leading to an increase in the metabotropic to ionotropic glutamate receptor ratio at glutamate release sites. The perisynaptic position of postsynaptic metabotropic glutamate receptors appears to be a general feature of glutamatergic synaptic organization and may apply to other G‐protein‐coupled receptors.
Acidic Calponin Cloned from Neural Cells is Differentially Expressed During Rat Brain Development
Authors: Ferhat Lotfi , Charton Gérard , Represa Alfonso , Ben‐Ari Yezekiel , der Terrossian Elisabeth , Khrestchatisky Michel 
Published: April 2006

AbstractCalponin is an actin‐, tropomyosin‐ and Ca2+ calmodulin‐binding protein that inhibits in vitro the actomyosin MgATPase. Basic and acidic variants of calponin have been described to date. Although the cerebral expression of calponin remained controversial for some time, transcripts encoding acidic calponin in the adult rat brain and calponin immunoreactivity in rat and pig brain and in cultured cerebellar cells have been reported. In the present work, we report the expression of acidic calponin mRNAs and the isolation of cDNAs encoding the full‐length acidic calponin in cultured neuronal and glial cells and in adult rat brain. Sequence analysis reveals that acidic calponin in the brain is identical to that previously described in rat aortic vascular smooth muscle. In situ hybridization shows that calponin is highly expressed during ontogenesis in granule cells of the dentate gyrus of the hippocampus, in all layers of the olfactory bulb and in cerebellar granule neurons of the external and internal layers. In the adult rat brain, calponin expression decreased in these fields, but increased in choroid plexus cells. Bergmann glial cells were also labelled by a calponin probe. The reverse transcription‐coupled polymerase chain reaction confirms that calponin mRNA levels are highest in the early stages of hippocampal development and that expression levels are low in adult hippocampi. The developmental expression pattern of brain acidic calponin suggests that calponin could be involved in contractile activity associated with neural cell proliferation or neuronal migration.
Non‐synaptic Release of ATP by Electrical Stimulation in Slices of Rat Hippocampus, Cerebellum and Habenula
Authors: Hamann Martine , Attwell David 
Published: April 2006

AbstractATP is thought to be a fast neurotransmitter in the medial habenula region of the brain, and may be coreleased with other transmitters, for example with glutamase in the hippocampus. We monitored ATP release in rat brain slices using the bioluminescent indicator system luciferin—luciferase. Electrical stimulation of the hippocampus, cerebellum or habenula led to ATP release, but this release was calcium‐independent and was not blocked by tetrodotoxin, or by other agents found to block ATP release from red blood cells. Although calcium‐dependent ATP release may occur in response to electrical stimulation, it appears to be overwhelmed by calcium‐independent release, which may result from electroporation of cells close to the stimulating electrode. Consistent with this, uptake into cells of the fluorescent dye Lucifer yellow was promoted by electrical stimulation. Our data undermine a previous suggestion, based on use of the luciferin‐luciferase technique, that ATP is synaptically released with glutamate in the hippocampus.
Activation of Multiple Metabotropic Glutamate Receptor Subtypes Prevents NMDA‐induced Excitotoxicity in Rat Hippocampal Slices
Authors: Pizzi Marina , Consolandi Ornella , Memo Maurizio , Spano PierFranco 
Published: April 2006

AbstractMetabotropic glutamate receptors (mGluRs) belong to a relative large receptor family consisting of multiple members with important roles in a number of brain functions. We report here that activation of mGluRs prevents the neurotoxic effect induced by N‐methyl‐D‐aspartate (NMDA) in slices from the rat hippocampus. Neuroprotection was elicited when slices were simultaneously exposed to both the selective mGluR agonist (±)‐1‐aminocyclopentane‐trans‐1,3‐dicarboxylic acid (tACPD) and NMDA. Persisting stimulation of mGluRs after the toxic exposure did not improve the survival of pyramidal or granular cells. The neuroprotection elicited by tACPD was also evoked by its active isomer, (1 S,3R)‐ACPD, and was prevented by the selective mGluR antagonist (+)‐α‐methyl‐4‐carboxyphenyl‐glycine (500 μM), confirming that mGluR activation is involved in the mechanism of action of tACPD. The effect of 100 μM tACPD was reproduced by 100 μM quisqualate, an agonist for mGluR1 and mGluR5, and by 1 μM of (2S,1's,2's)‐2‐carboxycyclopropyl‐glycine, a preferential agonist of mGluR2 and mGluR3 subtypes. No neuroprotection was induced by L‐2‐amino‐4‐phospnonobutyrate, a selective agonist for mGluR4, mGluR6, mGluR7 and mGluR8, at 500 μM. Since the NMDA‐mediated cell death in hippocampal slices is considered relevant to ischaemia‐induced brain injury, these results indicate that mGluRs may be important safety devices used by neurons to decrease their sensitivity to excitotoxic stimuli and increase their chance of survival.
Thalamic and Basal Forebrain Afferents Modulate the Development of Parvalbumin and Calbindin D28k Immunoreactivity in the Barrel Cortex of the Rat
Authors: Alcántara Soledad , Soriano Eduardo , Ferrer Isidro 
Published: April 2006

AbstractIn the adult barrel cortex of the rat the calcium‐binding proteins calbindin D28k (CALB) and parvalbumin (PARV) are found in separate populations of GABAergic nonpyramidal neurons. In layers II to IV of the barrel cortex most PARV‐immunoreactive neurons are likely to derive from a subpopulation of CALB‐immunoreactive neurons whose CALB immunoreactivity ceases when they begin to express PARV between the second and third postnatal weeks. The aim of this study was to investigate the influence of subcortical afferents on the neurochemical differentiation of cortical PARV‐ and CALB‐immunoreactive nonpyramidal neurons during development of the barrel cortex. We produced unilateral excitotoxic lesions with a single injection of ibotenic acid (0.5 μ, 0.05 M) in different subcortical nuclei in 7‐to 8‐day‐old rats. Lesions involving the ventroposterior thalamic nuclei resulted in delayed development of PARV and CALB immunoreactivity in the barrel cortex. One week after ibotenic acid injections a transient decrease in the number of PARV‐immunoreactive neurons in layer IV was observed, together with increased numbers of CALB‐immunoreactive neurons in all cortical layers. The number of nonpyramidal neurons displaying coexistence of PARV and CALB in the lesioned hemisphere also increased compared with the numbers in the control hemisphere or control littermates. In contrast, lesions affecting the globus pallidus, zona incerta and reticular thalamic nucleus transiently increased the number of PARV‐immunoreactive neurons in layers II and III, but had no effect on the number of CALB‐positive cells. From 3 weeks onwards no differences were found between control and iesioned hemispheres after injections into either the ventroposterior thalamic nuclei or the magnocellular basal forebrain. These results suggest that CALB and PARV expression in nonpyramidal cortical neurons can be reversibly modulated in opposite directions by different cortical afferents during postnatal development.
Selective Immunolesioning of the Basal Forebrain Cholinergic System Disrupts Short‐term Memory in Rats
Authors: Leanza G. , Muir J. , Nilsson O. G. , Wiley R. G. , Dunnett S. B. , Björklund A. 
Published: April 2006

AbstractSelective depletion of nerve growth factor receptor‐bearing neurons in the basal forebrain cholinergic nuclei by the immunotoxin 192 IgG‐saporin offers a new and highly useful tool for the study of the role of the forebrain cholinergic system in cognitive functions. In the present study, we have tested the effects of 192 IgG—saporin in an operant delayed matching‐to‐position task which has previously been used to discriminate between delay‐dependent learning impairments and delay‐independent disturbances of non‐mnemonic processes. Rats were first trained to criterion performance and then received intraventricular injections of 5 μg of 192 IgG—saporin 4 weeks prior to a second testing session. Rats with 192 IgG—saporin lesions displayed a significant delay‐dependent decline in performance compared to normal controls, indicating a deficit in short‐term memory. Administration of the muscarinic blocker scopolamine (0.5 mg/kg, i.p.) produced more pronounced impairment in the performance of the normal control rats across all delays, and induced further impairment also in animals with 192 IgG‐saporin lesions. These effects were not observed following control injections of methyl scopolamine, suggesting that the impairment induced by scopolamine was due to the blockade of central muscarinic receptors. No improvement in performance was observed in either group following systemic treatment with the muscarinic cholinergic agonist arecoline (1.0 mg/kg). Biochemical and morphological analyses confirmed the selective and severe (>90–95%) depletion of cholinergic neurons throughout the septal‐diagonal band area and the nucleus basalis region by the intraventricular 192 IgG—saporin treatment. Although the immunotoxin was observed to produce additional damage to the cerebellar Purkinje cells, no gross motor abnormalities were observed that could contribute to the effects on accuracy in the task used here. In conclusion, the results show that selective combined lesions of the basal forebrain cholinergic neurons in the septal—diagonal band area and nucleus basalis produce long‐lasting impairments in short‐term memory, thus providing further support for a role of this system in cognitive functions.
Brain‐derived Neurotrophic Factor Reverses Experience‐dependent Synaptic Modifications in Kitten Visual Cortex
Authors: Galuske Ralf A. W. , Kim Dae‐Shik , Castrén Eero , Thoenen Hans , Singer Wolf 
Published: April 2006

AbstractDuring a critical period of early postnatal development the functional architecture of the visual cortex is shaped by experience‐dependent circuit selection following a Hebbian mechanism. One consequence is that monocular deprivation (MD) leads to competitive repression of the input from the deprived eye. Recently it has been proposed that this process might involve activity‐dependent competition for neurotrophic substances because the synthesis of brain‐derived neurotrophic factor (BDNF) is regulated by visual input. Here we investigate the effects of intracortical infusion of BDNF and nerve growth factor (NGF) on MD effects in the visual cortex. Neuronal responses were monitored with optical and single‐unit recording techniques in the visual cortex of kittens that had been infused intracortically either with BDNF, NGF or cytochrome C while subjected to MD for 1 week during the peak of the critical period. NGF or cytochrome C had no effect on the consequences of MD. After BDNF treatment, by contrast, ocular dominance (OD) shifted towards the deprived eye in a zone extending 2.5–3.5 mm from the infusion cannula, and neurons lost their orientation selectivity. At intermediate distances both eyes activated the cortex equally well and responses were again tuned for orientation; at still larger distances OD was shifted towards the normal eye. Thus, BDNF antagonizes the functional effects of MD and at high concentrations causes paradoxical disconnection of non‐deprived afferents and a loss of orientation selectivity.
Pigmented Epithelium Sustains Cell Proliferation and Decreases Expression of Opsins and Acetylcholinesterase in Reaggregated Chicken Retinospheroids
Authors: Layer Paul G. , Rothermel Andrée , Hering Heike , Wolf Birgit , DeGrip Willem J. , Hicks David , Willbold Elmar 
Published: April 2006

AbstractWe investigated the effect of the retinal pigmented epithelium on cell proliferation and differentiation in rosetted retinospheroids, which are retina‐like spheres reaggregated in the complete absence of retinal pigmented epithelium from dissociated retinal cells of 6‐day‐old chick embryos in a rotation culture system. In spheroids raised in the absence of retinal pigmented epithelium (controls), acetylcholinesterase was expressed in cells of an inner nuclear‐like layer and their neuropil matrices. Moreover, the ratio between rods and cones was found to be approximately normal throughout the spheroid. When spheroids were cultured in the presence of retinal pigmented epithelium monolayers, cell proliferation in spheroids as determined by BrdU labelling was significantly increased and extended for 1 week, while acetylcholinesterase protein levels and specific activities in homogenates were decreased to ∼30%. At the same time, opsin immunoreactivity was completely suppressed within the spheroid and appeared slowly in cells around its periphery; i.e. the proportion of rhodopsin‐positive cells decreased from 14 to 3%. This study reveals that the retinal pigmented epithelium in vifro sustains cell proliferation but inhibits the differentiation of acetylcholinesterase‐positive cells and of photoreceptors.
The CCK‐B Agonist, BC264, Increases Dopamine in the Nucleus Accumbens and Facilitates Motivation and Attention After lntraperitoneal Injection in Rats
Authors: Ladurelle Nathalie , Keller Gérard , Blommaert Armand , Roques Bernard P. , Daugé Valérie 
Published: April 2006

AbstractAlthough it is known that panic attacks are triggered by the cholecystokinin fragment CCK4, the specific involvement of peripheral or central cholecystokinin CCK receptors in various adaptive processes such as emotion, memory and anxiety has yet to be demonstrated. With this aim, we have investigated the biochemical and pharmacological effects resulting from the administration of BC264, a highly potent and selective CCK‐B agonist able to cross the blood‐brain barrier. Very low doses of BC264 (μg/kg i.p.), increased the exploration of animals submitted to an unknown territory but were devoid of anxiogenic properties in the elevated plus maze. BC264 increased locomotion and rearings of rats newly placed in an open field and improved their spontaneous alternation in a Y‐maze. The use of vagotomized animals showed that the increased alternation induced by BC264 did not require an intact vagus nerve, unlike the locomotor activation. These behavioural effects, prevented by the prior i.p. administration of the CCK‐B antagonist L‐365,260 but not by the CCK‐A antagonist L‐364,718, were shown to depend on dopaminergic systems, since they were blocked by D1 (SCH23390, 25 μg/kg i.p.) or D2 (sulpiride, 50 or 100 mg/kg i.p.) antagonists. In addition, bilateral perfusion in freely moving rats of BC264 at pharmacologically active doses, using a newly designed microdialysis system, was found to increase the extracellular levels of DA, DOPAC and HVA in the anterior part of the nucleus accumbens. These results show that activation of CCK‐B receptors by BC264 does not produce anxiogenic‐like effects but appears to improve motivation and attention, whereas other CCK‐B agonists such as BocCCK4 induce anxiogenic responses. Several explanations, including the existence of different sub‐sites of the CCK‐B receptor, could account for these differential effects.
Tetrahydrobiopterin as a Mediator of PC12 Cell Prolifeiation Induced by EGF and NGF
Authors: Anastasiadis Panagiotis Z. , Bezin Laurent , Imerman Bruce A. , Kuhn Donald M. , Louie Marisa C. , Levine Robert A. 
Published: April 2006

AbstractEpidermal growth factor and nerve growth factor increased the proliferation of rat phaeochromocytoma PC12 cells through obligatory elevation of intracellular (6R)‐tetrahydrobiopterin (BH4). Epidermal growth factor and nerve growth factor increased intracellular BH4 by inducing GTP‐cyclohydrolase, the rate‐limiting enzyme in BH4 biosynthesis. Specific inhibitors of BH4 biosynthesis prevented growth factor‐induced increases in BH4 levels and proliferation. The induction of GTP cyclohydrolase, BH4 and cellular proliferation by nerve growth factor was mediated by CAMP. Elevation of BH4 biosynthesis occurred downstream from CAMP in the cascade used by nerve growth factor to increase proliferation. Thus, intracellular BH4 is an essential mediator of the proliferative effects of epidermal growth factor and nerve growth factor in PC12 cells.
Mouse Astrocytes Store and Deliver Brain‐derived Neurotrophic Factor Using the Non‐catalytic gp95trkB Receptor
Authors: Rubio Nazario 
Published: April 2006

AbstractA study of the brain‐derived neurotrophic factor (BDNF)‐binding capacity of pure astrocytes demonstrated that these cells bind and endocytose [125l]BDNF rapidly using the gp95trkb truncated receptor. A linear Scatchard plot indicated the presence of only one type of receptor that bound the ligand, with a low Kd of 1.24 × 10−8 M. There were an average of 36 468 copies of this receptor on untreated astrocytes. Interestingly, the neurotrophin was not degraded intracellularly, as demonstrated by HPLC experiments. Furthermore, the stored molecule was released by a mechanism regulated by the extracellular BDNF concentration as a bioactive neurotrophic molecule that supports neuron survival, in a time‐ and temperature‐dependent manner. The data demonstrate that astrocytes exert an active role in the bioavailability of this neurotrophin, which is further enhanced in an inflammatory‐like situation induced experimentally in culture using interferon‐SgM.