bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opposite effects of Zn on the in vitro binding of [3H]LY354740 to recombinant and native metabotropic glutamate 2 and 3 receptors
Authors: Malherbe Pari , Richards J. Grayson , Broger Clemens , Zenner Marie‐Thérèse , Messer Jürg , Kratzeisen Claudia , Nakanishi Shigetada , Mutel Vincent 
Published: September 2005

AbstractWe investigated the effect of Zn on agonist binding to both recombinant and native mGlu2 and mGlu3 receptors. Zn had a biphasic inhibitory effect on recombinant mGlu2 with IC50 values for the high‐ and low‐affinity components of 60 ± 10 µm and 2 ± 0.7 mm, respectively. Zn induced a complex biphasic effect of inhibition and enhancement of [3H]LY354740 binding to mGlu3. Observations with a series of chimeric mGlu2/3 receptors suggest that the Zn effect resides in the N‐terminal domain of mGlu2 and mGlu3. We observed that the His56 of mGlu2, which corresponds to Asp63 in mGlu3 was largely accountable for the second phase of the Zn effect. As revealed by quantitative receptor radioautography, the addition of up to 100 µm Zn to brain sections of wild‐type mice resulted in significant decreases in binding density in most brain regions. In particular, the mid‐molecular layer of the dentate gyrus (DGmol) and the CA1 lacunosum moleculare of hippocampus (CA1‐LMol) showed reductions of 62 and 67%, respectively. In contrast, the addition of 300 µm Zn to brain sections of mGlu2–/– mice caused large increases in binding density of 289 and 242% in DGmol and CA1‐LMol, respectively. Therefore, Zn might play a role as a physiological modulator of group II mGlu receptor function.
Subunits of the epithelial sodium channel family are differentially expressed in the retina of mice with ocular hypertension
Authors: Dyka Frank M. , May Christian A. , Enz Ralf 
Published: September 2005

AbstractGlaucoma is a prevalent cause of blindness, resulting in the apoptotic death of retinal ganglion cells and optic nerve degeneration. The disease is often associated with elevated intraocular pressure, however, molecular mechanisms involved in ganglion cell death are poorly understood. To identify proteins contributing to this pathological process, we analysed the retinal gene expression of DBA/2J mice that develop an elevated intraocular pressure by the age of 6 months with subsequent ganglion cell loss. In this study, we identified subunits of the epithelial sodium channel (ENaC) family that are specifically expressed under elevated intraocular pressure. Using reverse transcriptase polymerase chain reaction we observed a significant increase of α‐ENaC in the neuronal retina of DBA/2J mice when compared with control animals, while β‐ENaC and γ‐ENaC were not detectable in this tissue. Specific immune sera to ENaC subunits showed up‐regulation of α‐ENaC in synaptic and nuclear layers of the retina, and in the retinal pigment epithelium. Consistent with our polymerase chain reaction data, β‐ENaC was not detected by specific antibodies in the retina, while γ‐ENaC was only present in the retinal pigment epithelium under ocular hypertension. Finally, the increase of α‐ENaC gene expression in the neuronal retina and the retinal pigment epithelium was not observed in other tissues of DBA/2J mice. Since the intraocular pressure is regulated by the transport of aqueous humour across epithelial structures of the eye that in turn is associated with ion flux, the specific up‐regulation of ENaC proteins could serve as a protecting mechanism against elevated intraocular pressure.
Differential long‐term neuroadaptations of glutamate receptors in the basolateral and central amygdala after withdrawal from cocaine self‐administration in rats
Authors: Lu Lin , Dempsey Jack , Shaham Yavin , Hope Bruce T. 
Published: September 2005

AbstractHumans and laboratory animals remain highly vulnerable to relapse to cocaine‐seeking after prolonged periods of withdrawal from the drug. It has been hypothesized that this persistent cocaine relapse vulnerability involves drug‐induced alterations in glutamatergic synapses within the mesolimbic dopamine reward system. Previous studies have shown that cocaine self‐administration induces long‐lasting neuroadaptations in glutamate neurons of the ventral tegmental area and nucleus accumbens. Here, we determined the effect of cocaine self‐administration and subsequent withdrawal on glutamate receptor expression in the amygdala, a component of the mesolimbic dopamine system that is involved in cocaine seeking and craving induced by drug‐associated cues. Rats were trained for 10 days to self‐administer intravenous cocaine (6 h/day) or saline (a control condition) and were killed after one or 30 withdrawal days. Basolateral and central amygdala tissues were assayed for protein expression of the α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptor subunits (GluR1 and GluR2) and the NMDA receptor subunits (NR1, NR2A and NR2B). In the basolateral amygdala, GluR1 but not GluR2 levels were increased on days 1 and 30, NR2A levels were increased on day 1, and NR2B levels were decreased on day 30 of withdrawal from cocaine. In the central amygdala, GluR2 but not GluR1 levels were increased on days 1 and 30, NR1 levels were increased on day 30 and NR2A or NR2B levels were not altered after withdrawal from cocaine. These results indicate that cocaine self‐administration and subsequent withdrawal induces long‐lasting and differential neuroadaptations in basolateral and central amygdala glutamate receptors.
TYRA‐2 (F01E11.5): a Caenorhabditis elegans tyramine receptor expressed in the MC and NSM pharyngeal neurons
Authors: Rex Elizabeth , Hapiak Vera , Hobson Robert , Smith Katherine , Xiao Hong , Komuniecki Richard 
Published: September 2005

AbstractTyramine appears to regulate key processes in nematodes, such as pharyngeal pumping, and more complex behaviors, such as foraging. Recently, a Caenorhabditis elegans tyramine receptor, SER‐2, was identified that is involved in the TA‐dependent regulation of these processes. In the present study, we have identified a second C. elegans gene, tyra‐2 (F01E11.5) that encodes a tyramine receptor. This is the first identification of multiple tyramine receptor genes in any invertebrate. Membranes from COS‐7 cells expressing TYRA‐2 bind [3H]tyramine with high affinity with a Kd of 20 ± 5 nm. Other physiologically relevant biogenic amines, such as octopamine and dopamine, inhibit [3H]tyramine binding with much lower affinity (Kis of 1.55 ± 0.5 and 1.78 ± 0.6 μm, respectively), supporting the identification of TYRA‐2 as a tyramine receptor. Indeed, tyramine also dramatically increases GTPγS binding to membranes from cells expressing TYRA‐2 (EC50 of 50 ± 13 nm) and the TA‐dependent GTPγS binding is PTX‐sensitive suggesting that TYRA‐2 may couple to Gαi/o. Based on fluorescence from tyra::gfp fusion constructs, TYRA‐2 expression appears to be exclusively neuronal in the MC and NSM pharyngeal neurons, the AS family of amphid neurons and neurons in the nerve ring, body and tail. Taken together, these results suggest that TYRA‐2 encodes a second Gαi/o‐coupled tyramine receptor and suggests that TA‐dependent neuromodulation may be mediated by multiple receptors and more complex than previously appreciated.
Inhibition of phosphoinositide 3 kinase‐Akt (protein kinase B)–nuclear factor‐κB pathway by lovastatin limits endothelial–monocyte cell interaction
Authors: Prasad Ratna , Giri Shailendra , Nath Narender , Singh Inderjit , Singh Avtar K. 
Published: September 2005

AbstractIntegrity of the blood–brain barrier is essential for the normal functioning of CNS. Its disruption contributes to the pathobiology of various inflammatory neurodegenerative disorders. We have shown that the HMG‐CoA reductase inhibitor (lovastatin) attenuated experimental autoimmune encephalomyelitis (EAE, an inflammatory disease of CNS) in rodents by inhibiting the infiltration of mononuclear cells into the CNS. Here, using an in vitro system, we report that lovastatin inhibits endothelial–monocyte cell interaction by down‐regulating the expression of vascular cell adhesion molecule‐1 and E‐selectin by inhibiting the phosphoinositide 3 kinase (PI3‐kinase)/protein kinase B (Akt)/nuclear factor‐kappa B (NF‐κB) pathway in endothelial cells. It inhibits tumor necrosis factor alpha (TNFα)‐induced PI3‐kinase, Akt and NF‐κB activation in these cells. Co‐transfection of constitutively active forms of PI3‐kinase and Akt reversed the lovastatin‐mediated inhibition of TNFα‐induced adhesion, as well as activation of NF‐κB, indicating the involvement of the PI3‐kinase/Akt pathway in the interaction of adhesion molecules and the process of adhesion. This study reports that lovastatin down‐regulates the pathway affecting the expression and interaction of adhesion molecules on endothelial cells, which in turn restricts the migration and infiltration of mononuclear cells thereby attenuating the pathogenesis of inflammatory diseases.
Pro‐apoptotic activity of N‐myc in activation‐induced cell death of microglia
Authors: Jung Dae Young , Lee Heasuk , Suk Kyoungho 
Published: September 2005

AbstractBrain microglial cells are thought to undergo apoptosis following the exposure to inflammatory stimuli such as lipopolysaccharide (LPS) and IFNγ, which is considered as an autoregulatory mechanism to control their own activation state. Here, we report that N‐myc constitutes a novel apoptotic pathway of LPS/IFNγ‐activated microglia. The expression of N‐myc was synergistically enhanced by LPS and IFNγ in microglia. Tetracycline‐based conditional expression of N‐myc sensitized microglia to nitric oxide (NO)‐induced apoptosis. Knockdown of N‐myc expression using small interfering RNA (siRNA) attenuated LPS/IFNγ‐induced microglial apoptosis. An increase in N‐myc expression, however, did not affect microglial production of NO or TNFα. The synergistic effect of LPS/IFNγ on the microglial N‐myc induction was mediated through Janus kinase (JAK)/STAT1 (signal transducer and activator of transcription 1) pathway. Taken together, LPS/IFNγ‐induced N‐myc participated in the activation‐induced cell death of microglia by sensitizing the cells to NO‐induced apoptosis; however, N‐myc did not influence the processes of inflammatory activation of microglia.
mTOR/p70S6k signalling alteration by Aβ exposure as well as in APP‐PS1 transgenic models and in patients with Alzheimer's disease
Authors: Lafay‐Chebassier Claire , Paccalin Marc , Page Guylène , Barc‐Pain Stéphanie , Perault‐Pochat Marie Christine , Gil Roger , Pradier Laurent , Hugon Jacques 
Published: September 2005

AbstractIn Alzheimer's disease, neuropathological hallmarks include the accumulation of β‐amyloid peptides (Aβ) in senile plaques, phosphorylated tau in neurofibrillary tangles and neuronal death. Aβ is the major aetiological agent according to the amyloid cascade hypothesis. Translational control includes phosphorylation of the kinases mammalian target of rapamycin (mTOR) and p70S6k which modulate cell growth, proliferation and autophagy. It is mainly part of an anti‐apoptotic cellular signalling. In this study, we analysed modifications of mTOR/p70S6k signalling in cellular and transgenic models of Alzheimer's disease, as well as in lymphocytes of patients and control individuals. Aβ 1–42 produced a rapid and persistent down‐regulation of mTOR/p70S6k phosphorylation in murine neuroblastoma cells associated with caspase 3 activation. Using western blottings, we found that phosphorylated forms of mTOR and p70S6k are decreased in the cortex but not in the cerebellum (devoid of plaques) of double APP/PS1 transgenic mice compared with control mice. These results were confirmed by immunohistochemical methods. Finally, the expression of phosphorylated p70S6k was significantly reduced in lymphocytes of Alzheimer's patients, and levels of phosphorylated p70S6k were statistically correlated with Mini Mental Status Examination (MMSE) scores. Taken together, these findings demonstrate that the mainly anti‐apoptotic mTOR/p70S6k signalling is altered in cellular and transgenic models of Alzheimer's disease and in peripheral cells of patients, and could contribute to the pathogenesis of the disease.
Effect of N‐acetylaspartylglutamate (NAAG) on non‐quantal and spontaneous quantal release of acetylcholine at the neuromuscular synapse of rat
Authors: Malomouzh Artem I. , Nikolsky Eugen E. , Lieberman Edward M. , Sherman Jessica A. , Lubischer Jane L. , Grossfeld Robert M. , Urazaev Albert Kh. 
Published: September 2005

Abstract N‐Acetylaspartylglutamate (NAAG), known to be present in rat motor neurons, may participate in neuronal modulation of non‐quantal secretion of acetylcholine (ACh) from motor nerve terminals. Non‐quantal release of ACh was estimated by the amplitude of the endplate membrane hyperpolarization (H‐effect) caused by inhibition of nicotinic receptors by (+)‐tubocurarine and acetylcholinesterase by armin (diethoxy‐p‐nitrophenyl phosphate). Application of exogenous NAAG decreased the H‐effect in a dose‐dependent manner. The reduction of the H‐effect by NAAG was completely removed when N‐acetyl‐β‐aspartylglutamate (βNAAG) or 2‐(phosphonomethyl)‐pentanedioic acid (2‐PMPA) was used to inhibit glutamate carboxypeptidase II (GCP II), a presynaptic Schwann cell membrane‐associated ectoenzyme that hydrolyzes NAAG to glutamate and N‐acetylaspartate. Bath application of glutamate decreased the H‐effect similarly to the action of NAAG but N‐acetylaspartate was without effect. Inhibition of NMDA receptors by dl‐2‐amino‐5‐phosphopentanoic acid, (+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzocyclohepten‐5,10‐imine (MK801), and 7‐chlorokynurenic acid or inhibition of muscle nitric oxide synthase (NO synthase) by NG‐nitro‐l‐arginine methyl ester and 3‐bromo‐7‐nitroindazole completely prevented the decrease of the H‐effect by NAAG. These results suggest that glutamate, produced by enzymatic hydrolysis of bath‐applied NAAG, can modulate non‐quantal secretion of ACh from the presynaptic terminal of the neuromuscular synapse via activation of postsynaptic NMDA receptors and synthesis of nitric oxide (NO) in muscle fibers. NAAG also increased the frequency of miniature endplate potentials (mEPPs) generated by spontaneous quantal secretion of ACh, whereas the mean amplitude and time constants for rise time and for decay of mEPPs did not change.
Mice lacking glutamate carboxypeptidase II are protected from peripheral neuropathy and ischemic brain injury
Authors: Bacich Dean J. , Wozniak Krystyna M. , Lu X.‐C. May , O'Keefe Denize S. , Callizot Noelle , Heston Warren D. W. , Slusher Barbara S. 
Published: September 2005

AbstractExcessive glutamate release is associated with neuronal damage. A new strategy for the treatment of neuronal injury involves inhibition of the neuropeptidase glutamate carboxypeptidase II (GCP II), also known as N‐acetylated α‐linked acidic dipeptidase. GCP II is believed to mediate the hydrolysis of N‐acetyl‐aspartyl‐glutamate (NAAG) to glutamate and N‐acetyl‐aspartate, and inhibition of NAAG peptidase activity (by GCP II and other peptidases) is neuroprotective. Mice were generated in which the Folh1 gene encoding GCP II was disrupted (Folh1–/– mice). No overt behavioral differences were apparent between Folh1–/– mice and wild‐type littermates, with respect to their overall performance in locomotion, coordination, pain threshold, cognition and psychiatric behavioral paradigms. Morphological analysis of peripheral nerves, however, showed significantly smaller axons (reduced myelin sheaths and axon diameters) in sciatic nerves from Folh1–/– mice. Following sciatic nerve crush, Folh1–/– mice suffered less injury and recovered faster than wild‐type littermates. In a model of ischemic injury, the Folh1–/– mice exhibited a significant reduction (p < 0.05) in infarct volume compared with their wild‐type littermates when subjected to middle cerebral artery occlusion, a model of stroke. These findings support the hypothesis that GCP II inhibitors may represent a novel treatment for peripheral neuropathies as well as stroke.
A developmental profile of the levels of calcium pumps in chick cerebellum
Authors: Sepúlveda M. Rosario , Hidalgo‐Sánchez Matías , Mata Ana M. 
Published: September 2005

AbstractThe functional expression and distribution of intracellular ATPase (sarco(endo)plasmic reticulum Ca2+‐ATPase: SERCA) and plasma membrane Ca2+‐ATPase (PMCA) was analyzed in the developing chick cerebellum. The activity and Ca2+ uptake increase with development for both ATPases. However, the protein content increases with the stage of development only for SERCA, remaining constant for PMCA. Immunohistochemical assays showed that the ontogenesis of these ATPases goes along with definite stages of cerebellum histogenesis, and is complete at hatching. The SERCA is mainly distributed in Purkinje neurons, whereas the PMCA seems to be expressed initially in climbing fibers, shifting to soma and spiny branchlets of Purkinje cells at late embryonic stages. Granule cells express both ATPases according to their degree of maturity, whereas only PMCA is present in cerebellar glomeruli. These pumps are present in deep nuclei and the choroid plexus, although in this latter tissue their expression declines with development. The spatio‐temporal distribution of SERCA and PMCA must be closely related to their association with the development of specific cells and processes of the chick cerebellum.
Intracellular events mediating insulin‐like growth factor I‐induced oligodendrocyte development: modulation by cyclic AMP
Authors: Palacios Nuria , Sánchez‐Franco Franco , Fernández Miriam , Sánchez Isabel , Cacicedo Lucinda 
Published: September 2005

AbstractInsulin‐like growth factor I (IGF‐I) is a potent inducer of oligodendrocyte development and myelination. Although IGF‐I intracellular signaling has been well described in several cell types, intracellular mechanisms for IGF‐I‐induced oligodendrocyte development have not been defined. By using specific inhibitors of intracellular signaling pathways, we report here that the MAPK and phosphatidylinositol 3‐kinase signaling pathways are required for the full effect of IGF‐I on oligodendrocyte development in primary mixed rat cerebrocortical cell cultures. The MAPK activation, but not the phosphatidylinositol 3‐kinase activation, leads to phosphorylation of the cAMP response element‐binding protein, which is necessary for IGF‐I to induce oligodendrocyte development. cAMP, although it does not show any effect on oligodendrocyte development, has an inhibitory effect on IGF‐I‐induced oligodendrocyte development that is mediated by the cAMP‐dependent protein kinase. Furthermore, cAMP also has an inhibitory effect on IGF‐I‐dependent MAPK activation. This is a cAMP‐dependent protein kinase‐independent effect and probably contributes to the cAMP action on IGF‐I‐induced oligodendrocyte development.
Disruption of postsynaptic GABAA receptor clusters leads to decreased GABAergic innervation of pyramidal neurons
Authors: Li Rong‐wen , Yu Wendou , Christie Sean , Miralles Celia P. , Bai Jilin , LoTurco Joseph J. , De Blas Angel L. 
Published: September 2005

AbstractWe have used RNA interference (RNAi) to knock down the expression of the γ2 subunit of the GABAA receptors (GABAARs) in pyramidal neurons in culture and in the intact brain. Two hairpin small interference RNAs (shRNAs) for the γ2 subunit, one targeting the coding region and the other one the 3′‐untranslated region (UTR) of the γ2 mRNA, when introduced into cultured rat hippocampal pyramidal neurons, efficiently inhibited the synthesis of the GABAA receptor γ2 subunit and the clustering of other GABAAR subunits and gephyrin in these cells. More significantly, this effect was accompanied by a reduction of the GABAergic innervation that these neurons received. In contrast, the γ2 shRNAs had no effect on the clustering of postsynaptic α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors, postsynaptic density protein 95 (PSD‐95) or presynaptic glutamatergic innervation. A γ2‐enhanced green fluorescent protein (EGFP) subunit construct, whose mRNA did not contain the 3′‐UTR targeted by γ2 RNAi, rescued both the postsynaptic clustering of GABAARs and the GABAergic innervation. Decreased GABAAR clustering and GABAergic innervation of pyramidal neurons in the post‐natal rat cerebral cortex was also observed after in utero transfection of these neurons with the γ2 shRNAs. The results indicate that the postsynaptic clustering of GABAARs in pyramidal neurons is involved in the stabilization of the presynaptic GABAergic contacts.
Adenosine A2A receptors and metabotropic glutamate 5 receptors are co‐localized and functionally interact in the hippocampus: a possible key mechanism in the modulation of N‐methyl‐d‐aspartate effects
Authors: Tebano M. T. , Martire A. , Rebola N. , Pepponi R. , Domenici M. R. , Grò M. C. , Schwarzschild M. A. , Chen J. F. , Cunha R. A. , Popoli P. 
Published: September 2005

AbstractHippocampal metabotropic glutamate 5 receptors (mGlu5Rs) regulate both physiological and pathological responses to glutamate. Because mGlu5R activation enhances NMDA‐mediated effects, and given the role played by NMDA receptors in synaptic plasticity and excitotoxicity, modulating mGlu5R may influence both the physiological and the pathological effects elicited by NMDA receptor stimulation. We evaluated whether adenosine A2A receptors (A2ARs) modulated mGlu5R‐dependent effects in the hippocampus, as they do in the striatum. Co‐application of the A2AR agonist CGS 21680 with the mGlu5R agonist (RS)‐2‐chloro‐s‐hydroxyphenylglycine(CHPG) synergistically reduced field excitatory postsynaptic potentials in the CA1 area of rat hippocampal slices. Endogenous tone at A2ARs seemed to be required to enable mGlu5R‐mediated effects, as the ability of CHPG to potentiate NMDA effects was antagonized by the selective A2AR antagonist ZM 241385 in rat hippocampal slices and cultured hippocampal neurons, and abolished in the hippocampus of A2AR knockout mice. Evidence for the interaction between A2ARs and mGlu5Rs was further strengthened by demonstrating their co‐localization in hippocampal synapses. This is the first evidence showing that hippocampal A2ARs and mGlu5Rs are co‐located and act synergistically, and that A2ARs play a permissive role in mGlu5R receptor‐mediated potentiation of NMDA effects in the hippocampus.