bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron‐Melanin Interaction and Lipid Peroxidation: Implications for Parkinson's Disease
Authors: Ben‐Shachar Dorit , Riederer P. , Youdim M. B. H. 
Published: October 2006

Abstract: The vulnerability of substantia mgral (SN) melaninized dopamine neurons to neurodegeneration in Parkinson's disease and the selective increases of iron and basal lipid peroxidation in SN indicate that iron‐melanin interaction could be crucial to the pathogenesis of this disease. The present study describes, for the first time, the identification and characterization of a high‐affinity (KD= 13 nM) and a lower affinity (KD= 200 nM) binding site for iron on dopamine melanin. The binding of iron to melanin is dependent on pH and the concentration of melanin Iron dictators, U74500A, desferrioxamme, and to less extent 1,10‐phenanthroline and chlorpromazine, but not the Parkinson‐inducing neurotoxin, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine, can inhibit the binding of iron to melanin and iron‐induced lipid peroxidation. Although melanin atone diminishes basal lipid peroxidation in rat cortical homogenates, it can also potentiate that initiated by iron, a reaction inhibited by desferrioxamine. In the absence of an identifiable exogenous or endogenous neurotoxin in idiopathic Parkinson's disease, iron‐melanin interaction in pars compacta of SN may be a strong candidate for the cytotoxic component of oxygen radical‐induced neurodegeneration of meianinized dopamine neurons.
Modulation of Quinolinic and Kynurenic Acid Content in the Rat Brain: Effects of Endotoxins and Nicotinylalanine
Authors: Moroni Flavio , Russi Patrizia , Gallo‐Mezo Miguel Angel , Moneti Gloriano , Pellicciari Roberto 
Published: October 2006

Abstract: Quinolinic acid, an endogenous excitotoxin, and kynurenic acid, an antagonist of excitatory amino acid receptors, are believed to be synthesized from tryptophan after the opening of the indole ring. They were measured in the rat brain and other organs using gas chromatography‐mass spectrometry or HPLC. The enzyme indoleamine 2,3‐diox‐ygenase, capable of cleaving the indole ring of tryptophan, was induced by administering bacterial endotoxins to rats, which significantly increased the brain content of both quinolinic and kynurenic acids. Nicotinylalanine, an analogue of kynurenine, inhibited this endotoxin‐induced accumulation of quinolinic acid while potentiating the accumulation of‐kynurenic acid. The possibility of significantly increasing brain concentrations of kynurenic acid without a concomitant increase in quinolinic acid may provide a useful approach for studying the role of these electrophysiologically active tryptophan metabolites in brain function and preventing the possible toxic actions of abnormal synthesis of quinolinic acid.
Endo‐Oligopeptidase A., a Putative Enkephalin‐Generating Enzyme, in the Vertebrate Retina
Authors: Ferro E. S. , Hamassaki D. E. , Camargo A. C. M. , Britto L. R. G. 
Published: October 2006

Abstract: Endo‐oligopeptidase A., EC 3.4.22.19, converts small enkephalin‐containing peptides into the corresponding enkephalins in vitro. We investigated the presence of endooligopeptidase A in the retina and its possible colocalization with enkephalins in retinal neurons. The specific activity of endo‐oligopeptidase A found in pigeon retinae (30.3 ± 7.3 mU/mg, mean ± standard deviation) was four times higher than in rabbit retinae (7.0 ± 1.1 mU/mg). The enzyme activity was not modified by EDTA, but it was enhanced by dithiothreitol and inhibited by zinc and 5.5′‐dithiobis(2‐nitrobenzoic acid). Immunohistochemical experiments with a purified antiserum against rabbit endo‐oligopeptidase A revealed labeled neurons in both the inner nuclear layer and the ganglion cell layer of pigeon and rabbit retinae. Double‐labeling immunofluorescence experiments demonstrated that about 90% of neurons containing endo‐oligopeptidase A‐like immune‐reactivity also contained [Leu5)‐enkephalin‐like immuno‐reactivity. These colocalization results may represent an important step toward the demonstration of the possible involvement of endo‐oligopeptidase A in enkephalin generation in vivo.
Hippocampal Kindling in the Rat Is Associated with Time‐Dependent Increases in the Concentration of Glial Fibrillary Acidic Protein
Authors: Hansen Anette , Jørgensen Ole Steen , Bolwig Tom G. , Barry David I. 
Published: October 2006

Abstract: The effect of hippocampal kindling on the regional brain concentration of total glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes, was studied in partially kindled rats, and in fully kindled rats after a post‐kindling period of 24h, 1 week, and 2 months. GFAP concentration was measured in arbitrary units by dot‐blots. In the hippocampus, dentate gyrus, basolateral amygdala, pyriform cortex, and entorhinal cortex, limbic structures which are known to be involved in the kindling process, there was an increase in GFAP concentration which was maximal in the fully kindled animals studied after 24 h. In most brain areas, GFAP concentration was still elevated 1 week post‐kindling, but had declined to control level 2 months post‐kindling. A significant increase in GFAP was also found in septum, ventral pallidum/accumbens nucleus, and primary motor cortex of kindled rats with a post‐kindling period of 24h, whereas in several other brain regions GFAP was unchanged. These results suggest that astrocyte activation, indicative of degenerative changes in nearby neurons, is a transient and regional phenomenon in kindling occurring only during the development of the kindled state.
Differential Localization of Alternative Spliced Transcripts Encoding Inositol 1,4,5‐Trisphosphate Receptors in Mouse Cerebellum and Hippocampus: In Situ Hybridization Study
Authors: Nakagawa Toshiyuki , Shiota Chiyo , Okano Hideyuki , Mikoshiba Katsuhiko 
Published: October 2006

Abstract: Expression of inositol 1,4,5‐trisphosphate (InsP3) receptor subtypes was determined in mouse brain using oligonucleotide‐specific in situ hybridization. All subtypes, except one that deletes 120 bp from the full‐length InsP3 receptor cDNA, were expressed in cerebellar Purkinje cells. In hippocampus, various subtypes showed distinct expression patterns. These results suggest that regionally selective expression of InsP3 receptor subtypes may result in the generation of functionally distinct channels.
Repeated Idazoxan Increases Brain Imidazoline Receptors in Normotensive (WKY) but Not in Hypertensive (SHR) Rats
Authors: Olmos Gabriel , Miralles Antonio , Barturen Fernando , Garcìa‐Sevilla Jesús A. 
Published: October 2006

Abstract: The specific binding of [3H]idazoxan in the presence of 10−6M(−)‐adrenaline was used to evaluate the density of imidazoline receptors in the brain of spontaneously hypertensive (SHR) rats and sex‐and age‐matched normotensive Wistar‐Kyoto (WKY) rats. In SHR rats the density of imidazoline receptors (cerebral cortex, hypothalamus, and medulla oblongata) was not different from that in normotensive (WKY) rats. However, repeated treatment with idazoxan consistently increased (23–80%) the density of imidazoline receptors in the various brain regions of WKY rats but not in SHR rats. In normotensive Sprague‐Dawley rats, repeated treatment with the imidazoline drugs idazoxan and cirazoline also increased (33–37%) the density of imidazoline receptors in the cerebral cortex. The lack of regulation by idazoxan of the density of imidazoline receptors in the brain of SHR rats might reflect the existence of a relevant abnormality of these receptors in this genetic model of hypertension.
Differential Responses of Expressed Recombinant Human γ‐Aminobutyric AcidA Receptors to Neurosteroids
Authors: Lan Nancy C. , Gee Kelvin W. , Bolger Michael B. , Chen Jie Sheng 
Published: October 2006

Abstract: Neuroactive steroids, in particular 3α‐hydroxypregnanes, are allosteric modulators of the γ‐aminobutyric acidA (GABAA) receptor. Regionally selective expression of receptor subunit subtypes may account for differential responsiveness of tissues to GABAergic inhibition and ncurosteroid modulatory effects. the effect of 5α‐pregnan‐3α‐ol‐20‐one (epiallopregnanolone) on heterotropic cooperativity on the GABAA receptor complex has been studied in three subtypes of expressed recombinant human receptors and in cat brain and spinal cord. Steroid potentiation of [3H]flunitrazepam binding was greatest for the α1β1γ2 receptor complex, whereas α1β1γ2 and α2β1γ2 complexes showed < 100% enhancement in binding. Previous studies suggest that the spinal cord is devoid of α1, whereas cerebellum is rich in α1 subunits. Correspondingly, a differential enhancement of [3H]flunitrazepam binding in spinal cord (51%) versus cerebellum (28%) was also observed. The structure of neuroactive steroids is important in determining the extent of neuromodulatory activity. The 5β‐pregnanes, 5β‐pregnan‐3α‐ol‐20‐one (epipregnanolone) and 5β‐pregnan‐3α,21‐diol‐20‐one (5β‐tetrahydrodeoxycorticosterone), were both less potent than their corresponding 5α derivatives. A 3α‐hydroxyl group is essential for neuromodulatory activity in the expressed receptors, as demonstrated by the observation that 5α‐preg‐nan‐3β‐ol‐20‐one (allopregnanolone) and 4‐pregnen‐3,20‐dione (progesterone) were both inactive. The ability to screen synthetic molecules using expressed human receptors that selectively contain individual subunit subtype combinations may prove to be a powerful tool in the development of therapeutic agents that act as allosteric modulators of the GABAA receptor and other neurotransmitter receptors as well.
Activation of a Microtubule‐Associated Protein‐2 Kinase by Insulin‐Like Growth Factor‐I in Bovine Chromaffin Cells
Authors: Cahill Anne L. , Perlman Robert L. 
Published: October 2006

AbstractTreatment of bovine chromaffin cells with insulin‐like growth factor‐I (IGF‐I) caused the activation of a protein kinase that phosphorylates microtubule‐associated protein‐2 (MAP‐2) in vitro. Activation of MAP‐2 kinase by IGF‐I varied with the time of treatment (maximal at 10–15 min) and the concentration of IGF‐I (maximal at 10 nM). The IGF‐I‐activated MAP‐2 kinase was localized to the soluble fraction of chromaffin cell extracts and required Mg2+ for activity. The IGF‐I‐activated kinase also phosphorylated myelin basic protein, but had little or no activity toward his‐tones or ribosomal S6 protein. To examine the role of protein tyrosine phosphoryiation in the activation of the MAP‐2 kinase, we isolated phosphotyrosine (PTyr)‐containing proteins from chromaffin cells by immunoaffinity adsorption on anti‐PTyr‐Sepharose beads. Anti‐PTyr‐Sepharose eluates from IGF‐I‐treated cells showed increased MAP‐2 kinase activity; thus, the MAP‐2 kinase (or a closely associated protein) appears to be a PTyr‐containing protein. Treatment of anti‐PTyr‐Sepharose eluates or crude chromaffin cell extracts with alkaline phosphatase significantly decreased kinase activity toward myelin basic protein, indicating that phosphoryiation of the IGF‐I‐activated kinase is required for its activity.
Evidence for Atrial Natriuretic Peptide (ANP) Synthesis and the Presence of ANP‐Transducing Receptors in the Rat Olfactory Bulb
Authors: Gutkowska J. , Tremblay J. , Meyer R. , Marcinkiewicz M. , Nemer M. 
Published: October 2006

AbstractThis study demonstrates the presence of both atrial natriuretic peptide (ANP) precursor and ANP transcripts in the rat olfactory bulb (OB), a key brain structure involved in the generation of olfaction‐dependent behavior. In addition to synthesizing ANP, the OB contains ANP‐transducing receptors coupled to the guanylate cyclase system but it is devoid of ANP “clearance receptors.” The characterization of biologically active ANP receptors and the evidence for in situ ANP synthesis in this region of the CNS adds credence to the hypothesis that the peptide plays a putative role in olfaction.
Tellurium Blocks Cholesterol Synthesis by Inhibiting Squalene Metabolism: Preferential Vulnerability to This Metabolic Block Leads to Peripheral Nervous System Demyelination
Authors: Wagner‐Recio Maria , Toews Arrel D. , Morell Pierre 
Published: October 2006

AbstractInclusion of 1.1% elemental tellurium in the diet of postweanling rats produces a peripheral neuropathy due to a highly synchronous primary demyelination of sciatic nerve; this demyelination is followed closely by remyelination. Sciatic nerves from animals fed tellurium for various times were removed and incubated ex vivo for 1 h with [14C]acetate, and radioactivity incorporated into individual lipid classes was determined. In nerves from rats exposed to tellurium, there was a profound and selective block in the conversion of radioactive acetate to cholesterol. Another radioactive precursor, [3H]water, gave similar results. We suggest that tellurium feeding inhibits squalene epoxidase activity and that the consequent lack of cholesterol destabilizes myelin, thereby causing destruction of the larger internodes. Ex vivo incubation experiments were also carried out with liver slices. As with nerve, tellurium feeding caused accumulation in squalene of label from radioactive acetate, whereas labeling of cholesterol was greatly inhibited. Unexpectedly, however, incorporation of label from [3H]water into both squalene and cholesterol was increased. Relevant is the demonstration that liver was the primary site of bulk accumulation of squalene, which accounted for 10% of liver dry weight at 5 days. Thus, accumulation of squalene (and other mechanisms, possibly including up‐regulation of cholesterol biosynthetic pathways) drives squalene epoxidase activity at normal levels in liver even in the presence of inhibitors of this enzyme. This is reflected by continuing incorporation of [3H]water into cholesterol; incorporation of this precursor takes place at many of the postsqualene biosynthetic steps for sterol formation. [14C]Acetate entering the sterol pathway before squalene in liver is greatly diluted in specific activity when it reaches the large squalene pool, and thus increased squalene epoxidase activity does not transfer significant 14C label to sterols. In contrast to the situation with liver, synthesis of sterols is markedly depressed in sciatic nerve, and squalene does not accumulate to high levels.
Axonal Transport Reversal of Acetylcholinesterase Molecular Forms in Transected Nerve
Authors: Hässig Raymonde , Tavitian Bertrand , Pappalardo Francesca , Giamberardino Luigi Di 
Published: October 2006

AbstractReversal of anterograde rapid axonal transport of four molecular forms of acetylcholinesterase (AChE) was studied in chick sciatic nerve during the 24‐h period following a nerve transection. Reversal of AChE activity started ∼1 h after nerve transection, and all the forms of the enzyme, except the monomeric ones, showed reversal of transport. The quantity of enzyme activity reversed 24 h after transection was twofold greater than that normally conveyed by retrograde transport. We observed no leakage of the enzyme at the site of the nerve transection and no reversal of AChE activity transport in the distal segment of the severed nerve, a result indicating that the material carried by retrograde axonal transport cannot be reversed by axotomy. Thus, a nerve transection induces both quantitative and qualitative changes in the retrograde axonal transport, which could serve as a signal of distal injury to the cell body. The velocity of reverse transport, measured within 6 h after transection, was found to be 213 mm/day, a value close to that of retrograde transport (200 mm/day). This suggests that the reversal taking place in severed sciatic nerve is similar to the anterograde‐to‐retrograde conversion process normally occurring at the nerve endings.
Presence of Various Carbohydrate Moieties Including β‐Galactose and N‐Acetylglucosamine Residues on Solubilized Porcine Brain Neurokinin‐1/Substance P Receptors
Authors: Liu Ya Fang , Quirion Remi 
Published: October 2006

AbstractNeurokinin‐1 (NK‐1)/substance P (SP) receptors were solubilized using 10 mM 3‐[(cholamidopropyl)‐dimethylammonio]‐1‐propanesulfate from porcine striatal membranes (solubilization yield, 80%). In solubilized preparations, [3H]SP apparently bound to a single class of high‐affinity sites (KD= 0.82 ± 0.13 nM) as in membrane ho‐mogenates. The ligand selectivity pattern observed in both membrane and solubilized receptor preparations indicated that [Sar9, Met(O2)11]SP = SP ± senktide = [Nle10]neurokinin A4–10.This suggests the selective labeling of the NK‐1 receptor class in both assays. Solubilized receptors were retained on agarose‐coupled lectins that bind N‐acetylglucosamine‐galactose and β‐galactose (Ricinus communis I and Ricinus communis II), mannose (concanavalin A and lentil), and N‐ acetylglucosamine (wheat germ agglutinin) but not on lectins binding fucose (Lotus A) and N‐acetylgalactosamine (Dolichos biflorus A). Thus, it appears that porcine brain NK‐1/SP receptors are enriched with various carbohydrate moieties, β‐galactose and N‐acetylglucosamine‐galactose residues being especially abundant. This situation is rather different from that in various other members of the rhodopsin seven‐trans‐membrane receptor superfamily.
Effect of Unilateral Perinatal Hypoxic‐Ischemic Brain Injury in the Rat on Striatal Muscarinic Cholinergic Receptors and High‐Affinity Choline Uptake Sites: A Quantitative Autoradiographic Study
Authors: Kostic Vladimir , Przedborski Serge , Jackson‐Lewis Veraice , Cadet Jean Lud , Burke Robert E. 
Published: October 2006

AbstractThe binding characteristics and distribution of M1and M2 muscarinic cholinergic receptors and high‐affinity choline uptake sites were studied in the striatum of the rat at 3–4 and 9–12 weeks of age after exposure to unilateral perinatal hypoxic‐ischemic brain injury. High‐affinity choline uptake sites were labeled with [3H]hemicholinium‐3, M1 receptors with [3H]pirenzepine, and M2 receptors with [3H]AFDX 116. Saturation experiments revealed a significant decrease in the maximal binding capacity (Bmax) for [3H]pirenzepine‐labeled M1 receptors in the lesioned caudate/putamen complex in immature rats with moderate brain injury, in comparison with controls. In contrast, the Bmax value for [3H]hemicholinium‐3‐labeled high‐affinity choline uptake sites was significantly increased. No changes in dissociation constants (KD) were observed. These changes were most pronounced in the dorsolateral region of striatum. Striatal regional distribution of [3H]AF‐DX 116 was not affected. In mature rats, binding of [3H]pirenzepine returned to control values, whereas [3H]hemicholinium binding showed a persistent increase (23%). The increase in [3H]hemicholinium‐3 binding, as a specific marker of cholinergic nerve terminals, is consistent with our prior morphologic studies demonstrating relative preservation of cholinergic neurons and neuropil, and supports the concept that Striatal cholinergic systems are resistant to hypoxic‐ischemic injury.
Cyclic AMP Modulates Differentially the Release of Dopamine Induced by Hypoxia and Other Stimuli and Increases Dopamine Synthesis in the Rabbit Carotid Body
Authors: Pérez‐García M. T. , Almaraz L. , González C. 
Published: October 2006

AbstractWe have investigated the effects of different treatments that increase cyclic AMP levels on the in vitro synthesis and release of catecholamines in the rabbit carotid body. We also measured the rate of 45Ca2+ efflux from previously loaded carotid bodies under different conditions. Forskolin produced a dose‐dependent increase in the release of [3H]dopamine elicited by a hypoxic stimulus of medium intensity (Po2= 33 mm Hg) without altering basal [3H]dopamine release (100% O2‐equilibrated medium). At a concentration of 5 × 10‐‐6M, forskolin increased the release of [3H]dopamine induced by hypoxic stimuli of different intensities; the increase was maximal (498%) at the lowest intensity of hypoxic stimuli (Po2= 66 mm Hg), averaged 260% for hypoxic stimuli of intermediate intensity and 2 × 10‐‐4M cyanide, and was 150% under anoxia. Dibutyryl cyclic AMP (2 mM) and 3‐isobutyl‐1‐methylxanthine (0.5 mM) mimicked forskolin effects under hypoxic stimulation. Forskolin (5 × 10‐‐6M) also increased (180%) the release of [3H]dopamine induced by 20% CO2/pH 6.6, 2.5 × 10‐‐4M dinitrophenol, and 3 × 10‐‐5M ionomycin. Forskolin and 3‐isobutyl‐1‐methylxanthine were without effect on the release of [3H]dopamine elicited by 30 mM extracellular K+. Forskolin (5 × 10‐‐6M) augmented significantly the rate of 45Ca2+ efflux induced by hypoxic stimuli (Po2 of 33 and 66 mm Hg) and 2 × 10‐‐4M cyanide and showed a tendency to increase (20%) the 45Ca2+ efflux induced by dinitrophenol and low pH and to decrease (21%) the efflux induced by 30 mM K+ without altering the rate of efflux under basal conditions. Finally, forskolin (10‐‐5M) produced a 40% increase in the rate of [3H]dopamine synthesis from [3H]tyrosine. From the present and previously published observations, two physiological roles emerge for cyclic AMP in the carotid body: (a) The release of dopamine elicited by natural stimuli (low Po2 and low pH/high Pco2) is positively modulated by the associated increase in cAMP levels. In the case of the hypoxic stimulus, cyclic AMP may act on the O2‐sensing machinery and the exocytotic process, whereas in the case of the acidic stimuli, it may affect only the exocytotic process. (b) The activation of dopamine synthesis observed during hypoxic stimulation may be produced. at least in part, by the concomitant increase in level of cyclic AMP. via a cyclic AMP‐dependent phosphorylation of tyrosine hydroxylase.
GD3 Prevalence in Adult Rat Retina Correlates with the Maintenance of a High GD3‐/GM2‐Synthase Activity Ratio Throughout Development
Authors: Daniotti J. L. , Lancia C. A. , Rösner H. , Maccioni H. J. F. 
Published: October 2006

AbstractUnlike neurons from avian retina and other regions of avian and mammalian brain, neurons from mammalian retina not only contain gangliosides of the gangliotetraosyl ceramide series but also maintain a prevalence of GD3, a gangliosidc of the lactosylceramidc series characteristic of proliferative neural cells, when they are fully differentiated. We show here that GD3 is prevalent at all developmental periods of the rat retina from birth [50% of total gangliosidic N‐acetylneuraminic acid (Neu NAc)] to adult (30% of total gangliosidic Neu NAc). GD3‐synthase specific activity increased about 1.5‐fold from birth to day 7 and essentially plateaued thereafter. The GD3‐/GM2‐synthase specific activity ratio was compared in rat and chicken retina at early and late developmental stages. In chicken retina the ratio was about 0.7 at early (when GD3 is prevalent) and decreased to 0.07 at late (when GDI a is prevalent) developmental stages. In rat retina the ratio was about 13 and 6 at, respectively, early and late developmental stages. These findings suggest that the prevalence of GD3 and of other “b” pathway gangliosides in adult rat retina neurons could be due in part to the maintenance of a high GD3‐/GM2‐synthase activity ratio throughout development of the tissue.