bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of group I metabotropic glutamate receptors enhances efficacy of glutamatergic inputs to neonatal rat hypoglossal motoneurons in vitro
Authors: Sharifullina Elina , Ostroumov Konstantin , Nistri Andrea 
Published: September 2004

AbstractGroup I metabotropic glutamate receptors (mGluRs) are the main class of metabotropic receptors expressed in the hypoglossus nucleus. Their role in glutamatergic transmission was investigated using patch‐clamp recording from motoneurons in a neonatal rat brainstem slice preparation. After pharmacological block of γ‐aminobutyric acid and glycine‐mediated inhibition, under voltage‐clamp, the selective group I agonist (RS)‐3,5‐dihydroxyphenylglycine (DHPG) induced a motoneuron inward current by depressing a leak conductance, and strongly facilitated spontaneous glutamatergic synaptic currents. This effect was blocked by 7‐(hydroxyimino)cyclopropa[b]chromen‐1a‐carboxylate ethyl ester (CPCCOEt) and unaffected by 2‐methyl‐6‐(phenylethynyl)pyridine hydrochloride (MPEP), indicating a role for subtype 1 mGluRs. The frequency but not the amplitude of miniature glutamatergic currents was also enhanced by DHPG. Currents elicited by puffer application of (RS)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) in the presence of tetrodotoxin were also unchanged, suggesting that DHPG facilitated release of glutamate. Glutamatergic currents evoked by electrically stimulating the dorsomedullary reticular column premotoneurons were, however, depressed by DHPG in a CPCCOEt‐sensitive fashion. Neither CPCCOEt nor MPEP per se changed glutamatergic transmission. Under current‐clamp, even if DHPG depressed excitatory postsynaptic potentials, motoneuron spike threshold and time to peak were reduced so that facilitation of synaptic potential/spike coupling became apparent. We propose a wiring diagram to account for the differential action by DHPG on spontaneous and evoked transmission, based on the discrete distribution of subtype 1 mGluRs on glutamatergic afferents. Although under standard recording conditions there was insufficient ambient glutamate to activate mGluRs, such receptors were a powerful target to upregulate excitatory synaptic transmission and enhance signalling by hypoglossal motoneurons to tongue muscles.
Chronic l‐DOPA treatment increases extracellular glutamate levels and GLT1 expression in the basal ganglia in a rat model of Parkinson's disease
Authors: Robelet S. , Melon C. , Guillet B. , Salin P. , Kerkerian‐Le Goff L. 
Published: September 2004

AbstractThere is growing experimental evidence for the implication of glutamate‐mediated mechanisms both in the pathophysiology of Parkinson's disease and in the development of dyskinesias with long‐term administration of l‐3,4‐dihydroxyphenylalanine (l‐DOPA). However, the impact of this treatment on glutamate transmission in the basal ganglia has been poorly investigated. In this study, we examined the effects of 6‐hydroxydopamine‐induced lesion of nigral dopamine neurons with or without subsequent chronic l‐DOPA treatment on several parameters of glutamate system function in the rat striatum and substantia nigra pars reticulata. All the lesioned animals treated with l‐DOPA developed severe dyskinesias. Extracellular glutamate levels, measured by microdialysis in freely moving conditions, and gene expression of the glial glutamate transporter GLT1, assessed by in situ hybridization, were unaffected by dopamine lesion or l‐DOPA treatment alone, but were both markedly increased on the lesion side of rats with subsequent l‐DOPA treatment. No change in the expression of the vesicular glutamate transporters vGluT1 and vGluT2 was measured in striatum. These data show that chronic l‐DOPA treatment leading to dyskinesias increases basal levels of glutamate function in basal ganglia. The l‐DOPA‐induced overexpression of GLT1 may represent a compensatory mechanism involving astrocytes to limit glutamate overactivity and subsequent toxic processes.
Corticostriatal brain‐derived neurotrophic factor dysregulation in adult rats following prenatal stress
Authors: Fumagalli Fabio , Bedogni Francesco , Perez Jorge , Racagni Giorgio , Riva Marco Andrea 
Published: September 2004

AbstractPrenatal stress represents a well‐established experimental protocol resembling some features of schizophrenia, including deficits in social interactions, disruption of prepulse inhibition and enhanced response to psychomotor stimulants. In order to evaluate molecular changes that could participate in long‐lasting effects on brain function, we analysed the effects of prenatal stress on the expression of brain‐derived neurotrophic factor (BDNF), an important molecular determinant of synaptic plasticity and cellular homeostasis, in adult male rats under basal conditions as well as in response to a chronic stress. The main finding is that BDNF expression is reduced in the prefrontal cortex and striatum of prenatally stressed rats. Furthermore, when exposed to chronic stress in adulthood, these rats display an altered regulation of BDNF expression in these brain structures, implying that adverse life events during gestation may interfere with the expression and function of this neurotrophin at adulthood in a region‐specific manner. The dysregulation of corticostriatal BDNF expression might thus contribute to permanent alterations in brain functions leading to heightened susceptibility to psychiatric disorders.
Contribution of GABAergic inhibition to synaptic responses and LTD early in postnatal development in the rat superior colliculus
Authors: Mize R. Ranney , Salt Thomas E. 
Published: September 2004

AbstractWe studied the development of optic tract evoked field potentials (FP) in the rodent superior colliculus (SC) and the effect of GABA antagonists upon their development and upon induction of long‐term depression (LTD). Brain slices were cut from Lister Hooded rats. The optic tract was stimulated while recording from the superficial grey layer. GABAergic inhibition was assessed by adding 100 µm picrotoxin and 3 µm CGP55845 antagonists to block GABAA,B,C receptors. LTD was induced with a 50 Hz, 20 s tetanus. At age P2, the FP consisted only of a presynaptic spike. The GABA antagonists had no effect. By P4, the FP consisted of a presynaptic spike, a longer latency population spike, and a field excitatory postsynaptic potential (fEPSP). The fEPSP was slightly prolonged by the GABA antagonists at this age. By P7–P14, a prominent FP with trailing fEPSP was recorded. The GABA antagonists usually had a large effect, with the fEPSP increasing in both amplitude and duration. A mature FP was usually recorded in P15–P23 slices where the GABA antagonist effect remained substantial. LTD could be induced in 17 of 30 control slices from rats aged P4–P26. The average fEPSP amplitude after tetanus was 77.9% of control. Pre‐treatment with GABA antagonists produced a short‐term potentiation (average 114.0%), rather than LTD, in 14 of 19 cases. This STP was followed by a more prolonged potentiation in 12 of the 14 cases. We conclude that GABAergic inhibitory circuits mature before eye opening and that GABA contributes to induction of LTD in the developing SC.
Peripubertal environmental enrichment reverses the effects of maternal care on hippocampal development and glutamate receptor subunit expression
Authors: Bredy Timothy W. , Zhang Tie Yuan , Grant Rebecca J. , Diorio Josie , Meaney Michael J. 
Published: September 2004

AbstractMaternal care in the rat influences the development of cognitive function in the offspring through neural systems known to mediate activity‐dependent synaptic plasticity. The offspring of mothers that exhibit increased levels of pup licking/grooming (high‐LG mothers) show increased hippocampal N‐methyl‐d‐aspartate (NMDA) subunit mRNA expression, enhanced synaptogenesis and improved hippocampal‐dependent spatial learning in comparison with animals reared by low‐LG mothers. The effects of reduced maternal care on cognitive function are reversed with peripubertal environmental enrichment; however, the neural mechanisms mediating this effect are not known. In these studies we exposed the offspring of high‐ and low‐LG mothers to environmental enrichment from days 22 to 70 of life, and measured the expression of genes encoding for glutamate receptor subunits and synaptophysin expression as a measure of synaptic density. Environmental enrichment reversed the effects of maternal care on synaptic density and this effect was, in turn, associated with a reversal of the effect of maternal care on the NR2A and NR2B subunits of the NMDA receptor, as well as effects on (RS)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor subunits. Finally, direct infusion of an NR2B‐specific NMDA receptor antagonist into the hippocampus eliminated the effects of maternal care on spatial learning/memory in the Morris water maze. These findings suggest that: (1) the effects of maternal care are mediated by changes in NR2B gene expression; and (2) that environmental enrichment reverses the effects of reduced maternal care through the same genomic target, the NR2B gene, and possibly effects on other subunits of the NMDA and AMPA receptors.
Isoflurane modulates glutamatergic and GABAergic neurotransmission in the amygdala
Authors: Ranft Andreas , Kurz Jörg , Deuringer Martin , Haseneder Rainer , Dodt Hans‐Ulrich , Zieglgänsberger Walter , Kochs Eberhard , Eder Matthias , Hapfelmeier Gerhard 
Published: September 2004

AbstractAttempts have been made to attribute the particular features of general anaesthesia such as hypnosis, analgesia, amnesia and autonomic stability to certain brain regions. In the present study, we examined the effects of the commonplace volatile anaesthetic isoflurane on synaptic transmission in an in vitro slice preparation of the murine amygdala. Despite the established role of this limbic structure in the formation of aversive memories, conditioned fear and anxiety, as well as pain processing and regulation of sympathetic tone, the influence of volatile anaesthetics on synaptic signalling has not yet been investigated in this region of the brain. Evoked postsynaptic currents were monitored from principal neurons in the basolateral nucleus of the amygdala by means of patch‐clamp recording. The mixed postsynaptic currents were mediated by non‐NMDA, NMDA, GABAA and GABAB receptors. Isoflurane added to the perfusion medium reduced the strength of synaptic signalling following the activation of non‐NMDA, NMDA, and GABAB receptors, whereas the GABAA receptor‐mediated responses were enhanced. The overall reduction of neuronal excitability was also reflected in a reduction of field potential amplitudes. Isoflurane neither changed the membrane resting potential nor the input resistance of principal neurons in the amygdala. The present results may contribute to the understanding of how stress reactions and long‐lasting neuroplastic processes are suppressed under general anaesthesia.
RFa‐related peptides are algogenic: evidence in vitro and in vivo
Authors: Yudin Yevgen K. , Tamarova Zinayida A. , Ostrovskaya Olga I. , Moroz Leonid L. , Krishtal Oleg A. 
Published: September 2004

AbstractRFamide (RFa)‐related peptides modulate pain processing in the mammalian CNS. The effects of these peptides are generally considered as ‘anti‐opioid’. They also decrease the rate of desensitization of acid‐sensing ionic channels (ASICs), putative nociceptors in dorsal root ganglia neurons [C. Askwith et al. (2000) Neuron, 26, 133–141]. We have tested the role of mollusc‐derived peptide, FMRFa (Phe‐Met‐Arg‐Phe‐amide) and its synthetic analogues in peripheral nociception. Here we demonstrate that RFa‐related peptides powerfully excite the majority of C‐fibres in the skin–nerve preparation of rat: 76% of 55 tested fibres with the conduction velocity below 2 m/s responded with long‐lasting discharges to the application of peptides (20 µm). When injected subcutaneously in vivo (mice), they initiate nociceptive behaviour. We confirm the data on humans [S. Ugawa et al. (2002) J. Clin. Invest., 110, 1185–1190]: the activation of C‐fibres by acid is inhibited by channel blocker of ASICs, amiloride. However, there is no correlation in the sensitivity of C‐fibres to RFa peptides, protons and amiloride: 74% of tested RFa‐sensitive C‐fibres were insensitive to protons and in 67% of cases the response to peptides was insensitive to amiloride. Thus, powerful excitatory/algogenic action of RFa‐related peptides cannot be interpreted solely in terms of their interaction with ASICs. The peptides do not activate any conductance in the somatic membrane of dorsal root ganglion neurons of rats and probably affect still unidentified molecular target(s) responsible for nociceptive signalling.
Genomics of cellulose biosynthesis in poplars
Authors: Joshi Chandrashekhar P. , Bhandari Suchita , Ranjan Priya , Kalluri Udaya C. , Liang Xiaoe , Fujino Takeshi , Samuga Anita 
Published: September 2004

SummaryGenetic improvement of cellulose production in commercially important trees is one of the formidable goals of current forest biotechnology research. To achieve this goal, we must first decipher the enigmatic and complex process of cellulose biosynthesis in trees. The recent availability of rich genomic resources in poplars make Populus the first tree genus for which genetic augmentation of cellulose may soon become possible. Fortunately, because of the structural conservation of key cellulose biosynthesis genes between Arabidopsis and poplar genomes, the lessons learned from exploring the functions of Arabidopsis genes may be applied directly to poplars. However, regulation of these genes will most likely be distinct in these two‐model systems because of their inherent biological differences. This research review covers the current state of knowledge about the three major cellulose biosynthesis‐related gene families from poplar genomes: cellulose synthases, sucrose synthases and korrigan cellulases. Furthermore, we also suggest some future research directions that may have significant economical impacts on global forest product industries.
Mitochondrial mechanisms of neural cell apoptosis
Authors: Polster Brian M. , Fiskum Gary 
Published: September 2004

AbstractThe importance of calcium overload, mitochondrial dysfunction, and free radical generation to neuropathological processes has been recognized for many years. Only more recently has evidence accumulated that the programmed cell death process of apoptosis plays an integral role not only in the development of the nervous system, but in the loss of cells following acute neurological insults and chronic disease. In 1996 came the landmark discovery that cytochrome c, an evolutionary old and essential component of the respiratory chain, has a second and deadly function when it escapes the mitochondrion: triggering the cell death cascade. A flurry of activity has since ensued in an effort to understand the mechanistic events associated with mitochondrial permeabilization during apoptosis and regulation by an enigmatic family of proteins characterized by homology to the proto‐oncogene Bcl‐2. This review discusses the evidence for various release mechanisms of apoptotic proteins (e.g. cytochrome c) from neural cell mitochondria, focusing particularly on roles for calcium, Bax, p53, and oxidative stress. The need for new drugs that act at the level of the mitochondrion to prevent apoptosis is also highlighted.
Functional dissociation of apelin receptor signaling and endocytosis: implications for the effects of apelin on arterial blood pressure
Authors: Messari Said El , Iturrioz Xavier , Fassot Celine , De Mota Nadia , Roesch Darren , Llorens‐Cortes Catherine 
Published: September 2004

AbstractApelin is a novel neuropeptide involved in the regulation of body fluid homeostasis and cardiovascular functions. It acts through a G protein‐coupled receptor, the APJ receptor. We studied the structure–activity relationships of apelin at the rat apelin receptor, tagged at its C‐terminal end with enhanced green fluorescent protein and stably expressed in CHO cells. We evaluated the potency of N‐ and C‐terminal deleted fragments of K17F to bind with high affinity to the apelin receptor, and to inhibit cAMP production and to induce apelin receptor internalization. We first characterized the internalization and trafficking of the rat apelin receptor. This receptor was internalized via a clathrin‐dependent mechanism and our results suggest that receptor trafficking may follow a recycling pathway. We then tried to identify the amino acids of K17F required for apelin activity. The first five N‐terminal and the last two C‐terminal amino acids of K17F were not essential for apelin binding or the inhibition of cAMP production. However, the full‐length sequence of K17F was the most potent inducer of apelin receptor internalization because successive N‐terminal amino‐acid deletions progressively reduced internalization and the removal of a single amino acid at the C‐terminus abolished this process. Finally, the most novel observation of this work is that hypotensive actions of apelin peptides correlate best with the ability of those ligands to internalize. Thus, apelin receptor signaling and endocytosis are functionally dissociated, possibly reflecting the existence of several conformational states of this receptor, stabilized by the binding of different apelin fragments to the apelin receptor.
Erk1/2 but not PI3K pathway is required for neurotrophin 3‐induced oligodendrocyte differentiation of post‐natal neural stem cells
Authors: Hu Xinhua , Jin Lu , Feng Linyin 
Published: September 2004

AbstractNeurotrophin 3 (NT3) induces mouse cortical stem cells to an asymmetric division from a symmetric division, suggesting that NT3 may work as an early differentiative signal for neural stem cells (NSCs). Here, using cultured post‐natal hippocampal stem cells as a model, we demonstrated that NT3‐stimulation causes NSCs to differentiate into oligodendrocyte precursors (OLPs) through an extracellular signal‐related kinase1/2 (Erk1/2)‐dependent pathway. Following the treatment of NT3 for 24 h, NSCs differentiated into more OLPs and fewer neurons, whereas the proliferation and survival of OLPs were not affected. NT3 induced a series of intracellular responses including enhancement of phosphorylation of Erk1/2 or Akt and increase of expression of oligodendrocyte lineage gene (Olig)‐1, a transcriptional factor known to participate in oligodendrocyte development. Application of U0126, a specific inhibitor of MEK1/2 which are upstream to Erk1/2, blocked the phosphorylation of Erk1/2, suppressed the expression of Olig‐1 and prevented NSC differentiation into OLPs in response to NT3 stimulation. Blockade of TrkC also inhibited the differentiation of NSCs to OLPs induced by NT3. However, administration of LY294002, an inhibitor of phosphatidylinositol 3 kinase (PI3K), blocked the phosphorylation of Akt but did not affect the effect of NT3 on the expression of Olig‐1 and on NSC differentiation into OLPs. Taken together, these results suggest that NT3 induce NSCs to differentiate into OLPs by enhancing the expression of Olig‐1 through an Erk1/2‐dependent pathway.
PEN‐2 enhances γ‐cleavage after presenilin heterodimer formation
Authors: Shiraishi Hirohisa , Sai Xiaorei , Wang Hua‐Qin , Maeda Yasuhiro , Kurono Yukihisa , Nishimura Masaki , Yanagisawa Katsuhiko , Komano Hiroto 
Published: September 2004

AbstractThe presenilin (PS) complex, including PS, nicastrin, APH‐1 and PEN‐2, is essential for γ‐secretase activity, which is required for amyloid β‐protein (Aβ) generation. However, the precise individual roles of the three cofactors in the PS complex in Aβ generation remain to be clarified. Here, to distinguish the roles of PS cofactors in γ‐secretase activity from those in PS endoproteolysis, we investigated their roles in the γ‐secretase activity reconstituted by the coexpression of PS N‐ and C‐terminal fragments (NTF and CTF) in PS‐null cells. We demonstrate that the coexpression of PS1 NTF and CTF forms the heterodimer and restores Aβ generation in PS‐null cells. The generation of Aβ was saturable at a certain expression level of PS1 NTF/CTF, while the overexpression of PEN‐2 alone resulted in a further increase in Aβ generation. Although PEN‐2 did not enhance PS1 NTF/CTF heterodimer formation, PEN‐2 expression reduced the IC50 of a specific γ‐secretase inhibitor, a transition state analogue, for Aβ generation, suggesting that PEN‐2 expression enhances the affinity or the accessibility of the substrate to the catalytic site. Thus, our results strongly suggest that PEN‐2 is not only an essential component of the γ‐secretase complex but also an enhancer of γ‐cleavage after PS heterodimer formation.
Counteraction of axonal growth inhibitory properties of Semaphorin 3A and myelin‐associated proteins by a synthetic neurotrophic compound
Authors: Hanbali Mazen , Bernard Frédéric , Berton Caroline , Gatineau Gilles , Perraut Martine , Aunis Dominique , Luu Bang , Bagnard Dominique 
Published: September 2004

AbstractOne of the reasons for the lack of nerve regeneration in the CNS is the formation of a glial scar over‐expressing multiple inhibitory factors including myelin‐associated proteins and members of the Semaphorin family. Innovative therapeutic strategies must stimulate axon extension across the lesion site despite this inhibitory molecular barrier. We recently developed a synthetic neurotrophic compound combining an ω‐alkanol with a retinol‐like cycle (3‐(15‐hydroxy‐pentadecyl)‐2,4,4,‐trimethyl‐cyclohexen‐2‐one (tCFA15)). Here, we demonstrate that tCFA15 is able to promote cortical axon outgrowth in vitro even in the presence of the inhibitory Semaphorin 3A and myelin extracts. This growth‐promoting effect is selectively observed in axons and requires multiple growth‐associated intracellular pathways. Our results illustrate the potential use of synthetic neurotrophic compounds to promote nerve regeneration by counteracting the axonal growth inhibition triggered by glial scar‐associated inhibitory factors.
Modulation of extracellular signal‐regulated kinase (ERK) activity by acute and chronic opioid treatment in neuronal and glial cell lines
Authors: Moulédous Lionel , Diaz Miguel F. , Gutstein Howard B. 
Published: September 2004

AbstractAcute mu opioid application has been shown to activate extracellular signal‐related kinases (ERKs) in various non‐neural cell lines. However, ERK activation in neuronal cells following acute morphine treatment is more questionable. Moreover, the ERK activation phenomenon observed in vivo after withdrawal of chronic opioids has never been demonstrated in vitro. The goal of this study was to determine if mu agonist treatment induced ERK activation acutely or after withdrawal of chronic opioids in one glial and three neuronal cell lines. We found that acute application of opioids was not able to activate ERK in neuronal cell lines but was able to activate ERK in a glial cell line. In another set of experiments, cells were chronically treated with escalating doses of a mu opioid agonist. After 8 days, the agonist was removed from the media and naloxone applied. Acute ERK activation was not seen in any tested cell line after agonist removal. These findings suggest that opioids may acutely activate ERK in non‐neuronal cells, and that the acute ERK activation observed in some brain regions during opioid withdrawal in vivo might be mediated by indirect effects on neuronal cells.