bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphine withdrawal‐induced c‐fos expression in the hypothalamic paraventricular nucleus is dependent on the activation of catecholaminergic neurones
Authors: Laorden M. Luisa , Núñez Cristina , Almela Pilar , Milanés M. Victoria 
Published: March 2003

AbstractWe previously demonstrated that morphine withdrawal induced hyperactivity of noradrenergic pathways innervating the hypothalamic paraventricular nucleus (PVN) in rats, in parallel with an increase in the neurosecretory activity of the hypothalamus–pituitary–adrenocortical (HPA) axis, as evaluated by corticosterone release. These neuroendocrine effects were dependent on stimulation of α‐adrenoceptors. In the present study, Fos immunostaining was used as a reflection of neuronal activity and combined with immunostaining for tyrosine hydroxylase (TH) for immunohistochemical identification of active neurones during morphine withdrawal. Dependence on morphine was induced by 7‐day chronic subcutaneous implantation of six morphine pellets (75 mg). Morphine withdrawal was precipitated by administration of naloxone (5 mg/kgsubcutaneously) on day 8. Fos immunoreactivity in the PVN and also in the nucleus tractus solitarius (NTS)‐A2 and ventrolateral medulla (VLM)‐A1 cell groups, which project to the PVN, increased during morphine withdrawal. Following withdrawal, Fos immunoreactivity was present in most of the TH‐positive neurones of the A2 and A1 neurones. In a second study, the effects of administration of adrenoceptor antagonists on withdrawal‐induced Fos expression in the PVN were studied. Pre‐treatment with α1‐ or α2‐adrenoceptor antagonists, prazosin (1 mg/kg intraperitoneally) and yohimbine (1 mg/kg intraperitoneally), respectively, 20 min before naloxone administration to morphine‐dependent rats markedly reduced Fos expression in the PVN. Similarly, pre‐treatment with the β antagonist, propranolol (3 mg/kg intraperitoneally), significantly prevented withdrawal‐induced Fos expression. Collectively, these results suggest the hypothesis that noradrenergic neurones in the brainstem innervating the PVN are active during morphine withdrawal, and that activation of transcriptional responses mediated by Fos in the HPA axis following withdrawal are dependent upon hypothalamic α‐ and β‐adrenoceptors.
Neurokinin‐1 (NK‐1) receptor antagonists abrogate methamphetamine‐induced striatal dopaminergic neurotoxicity in the murine brain
Authors: Yu Jing , Cadet Jean Lud , Angulo Jesus A. 
Published: March 2003

AbstractMethamphetamine (METH) is an addictive substance that also causes extensive neural degeneration in the central nervous system. Because METH augments striatal substance P (SP) levels, we hypothesized that this neuropeptide plays a role in methamphetamine‐induced toxicity and neural damage in the striatum. In this study we present evidence demonstrating that signaling through the neurokinin‐1 (NK‐1) receptor by SP plays an important role in methamphetamine‐induced toxicity in the striatum. We tested the effects of the selective NK‐1 receptor antagonists WIN‐51,708 and L‐733,060 on several markers of dopaminergic terminal toxicity in the mouse striatum. Administration of NK‐1 receptor antagonist prevented the loss of dopamine transporters assessed by autoradiography and western blotting, the loss of tissue dopamine assessed by high‐pressure liquid chromatography, and the loss of tyrosine hydroxylase, as well as the induction of glial fibrillary acidic protein determined by western blotting. Pre‐treatment with NK‐1 receptor antagonist had no effect on METH‐induced hyperthermia. Pre‐exposure of mice to either of the NK‐1 receptor antagonists alone was without effect on all of these neurochemical markers. These results provide the first evidence that tachykinins, particularly SP, acting through NK‐1 receptors, play a crucial role in the pathogenesis of nigrostriatal dopaminergic terminal degeneration induced by METH. This finding could lead to novel therapeutic strategies to offset drug addictions as well as in the treatment of a number of disorders including Parkinson's and Huntington's diseases.
Group‐I metabotropic glutamate receptors, mGlu1a and mGlu5a, couple to extracellular signal‐regulated kinase (ERK) activation via distinct, but overlapping, signalling pathways
Authors: Thandi Sukhwinder , Blank Jonathan L. , Challiss R. A. John 
Published: March 2003

AbstractThe coupling of the group I metabotropic glutamate receptors, mGlu1a and mGlu5a, to the extracellular signal‐regulated protein kinase (ERK) pathway has been studied in Chinese hamster ovary cell‐lines where receptor expression is under inducible control. Both mGlu receptors stimulated comparable, robust and agonist concentration‐dependent ERK activations in the CHO cell‐lines. The mGlu1a receptor‐mediated ERK response was almost completely attenuated by pertussis toxin (PTx) pretreatment, whereas the mGlu5a‐ERK response, and the phosphoinositide response to activation of either receptor, was PTx‐insensitive. mGlu1a and mGlu5a receptor coupling to ERK occurred via mechanisms independent of phosphoinositide 3‐kinase activity and intracellular and/or extracellular Ca2+ concentration. While acute treatment with a protein kinase C (PKC) inhibitor did not attenuate agonist‐stimulated ERK activation, down‐regulation of PKCs by phorbol ester treatment for 24 h did attenuate both mGlu1a and mGlu5a receptor‐mediated responses. Further, inhibition of Src non‐receptor tyrosine kinase activity by PP1 attenuated the ERK response generated by both receptor subtypes, but only mGlu1a receptor‐ERK activation was attenuated by PDGF receptor tyrosine kinase inhibitor AG1296. These findings demonstrate that, although expressed in a common cell background, these closely related mGlu receptors utilize different G proteins to cause ERK activation and may recruit different tyrosine kinases to facilitate this response.
Rat MYH, a glycosylase for repair of oxidatively damaged DNA, has brain‐specific isoforms that localize to neuronal mitochondria
Authors: Englander Ella W. , Hu Zhaoyong , Sharma Abha , Lee Heung‐Man , Wu Zhao‐Hui , Greeley George H. 
Published: March 2003

AbstractMitochondrial genomes are exposed to a heavy load of reactive oxygen species (ROS) that damage DNA. Since in neurons, mitochondrial DNA integrity must be maintained over the entire mammalian life span, neuronal mitochondria most likely repair oxidatively damaged DNA. We show that theEscherichia coliMutY DNA glycosylase homolog (MYH) in rat (rMYH) involved in repair of oxidative damage is abundantly expressed in the rat brain, with isoforms that are exclusive to brain tissue. Confocal microscopy and western analyses reveal localization of rMYH in neuronal mitochondria. To assess involvement of MYH in the neuronal response to oxidative DNA damage, we used a rat model of respiratory hypoxia, in which acutely reduced blood oxygenation leads to generation of superoxide, and formation and subsequent removal of 8‐hydroxy‐2′‐deoxyguanosine (8OHdG). Removal of 8OHdG is accompanied by a spatial increase in rMYH immunoreactivity in the brain and an increase in levels of one of the three mitochondrial MYH isoforms, suggesting that inducible and non‐inducible MYH isoforms exist in the brain. The mitochondrial localization of oxidative DNA damage repair enzymes in neurons may represent a specialized neuronal mechanism that safeguards mitochondrial genomes in the face of routine and accidental exposures to heavy loads of injurious ROS.
Long‐lasting occupancy of central nicotinic acetylcholine receptors after smoking: a PET study in monkeys
Authors: Valette Héric , Bottlaender Michel , Dollé Frédéric , Coulon Christine , Ottaviani Michèle , Syrota André 
Published: March 2003

AbstractThe aim of this study was to compare the degree of occupancy of central nicotinic acetylcholine receptors (nAChR) in isoflurane anaesthetized baboon brain following inhalation of tobacco smoke (one cigarette containing 0.9 mg nicotine) or i.v. nicotine (0.6 mg i.v.). [18F]Fluoro‐A‐85380 and positron emission tomography (PET) were used to assess the distribution volumes (DV) of the radiotracer in selected brain areas using a one‐compartment model. Eighty minutes after nicotine i.v., DV was reduced by 50 and 66% in the thalamus and putamen, respectively. Six hours after nicotine, a reduction in DV (27% in the thalamus) was still observed. Eighty minutes after inhalation of tobacco smoke, DV was decreased by 52 and 65% in the thalamus and putamen, respectively. Previous PET experiments have demonstrated a short‐lasting interaction of [11C]nicotine with nAChRs. Thus, we hypothesized that a metabolite of nicotine with high affinity and long half‐live (several hours) could bind at nAChRs. Eighty minutes after a high dose of nornicotine (0.5 mg i.v.), DV was reduced by 53 and 31% in thalamus and putamen, respectively. No significant effect was observed following 0.15 mg nornicotine. Therefore, nornicotine could contribute to the long‐lasting occupancy of central nAChRs after smoking.
Synaptic activity induces signalling to CREB without increasing global levels of cAMP in hippocampal neurons
Authors: Pokorska Anna , Vanhoutte Peter , Arnold Fiona J. L. , Silvagno Francesca , Hardingham Giles E. , Bading Hilmar 
Published: March 2003

AbstractNuclear calcium signals associated with electrical activation of neurons can control the activity of the transcription factor cAMP‐response element binding protein (CREB). Yet, cAMP is thought to be the key messenger that links synaptic activity to the regulation of CREB‐mediated transcription. It is generally assumed that synaptic activity increases the intracellular levels of cAMP; this causes activation of the cAMP‐dependent protein kinase (PKA) that regulates CREB‐mediated transcription either directly or through controlling nuclear signalling of the MAP kinases/extracellular signal‐regulated kinases (ERK1/2) pathway. Here we show that, in hippocampal neurons, synaptic activity failed to increase global levels of cAMP that would be required for the cAMP‐PKA system to induce nuclear events. Even near‐continuous bursting of action potentials, giving rise to large nuclear calcium signals and robust CREB‐dependent transcription, left global intracellular levels of cAMP unchanged. These results suggest that the cAMP‐PKA system does not function as the transducer of synaptic signals to the nucleus. They indicate that the known inhibitory effects of blockers of PKA on gene expression and long‐lasting plasticity triggered by calcium entry reflect a gating function of basal activity of PKA that renders neurons permissive for nuclear calcium‐regulated, CREB/CBP‐dependent gene expression.
Developmental regulation of nicotinic acetylcholine receptor‐mediated [3H]norepinephrine release from rat cerebellum
Authors: O'Leary K. T. , Leslie F. M. 
Published: March 2003

AbstractPresynaptic modulation of synaptic transmission is the primary function of central nicotinic acetylcholine receptors (nAChRs) in developing and adult brain. nAChR activation regulates release of various neurotransmitters, including norepinephrine (NA). Given evidence that NA may serve a critical functional role in cerebellar development, we have undertaken studies to determine whether nAChRs modulate NA release in developing cerebellum. In vitro experiments using cerebellar slices examined the effects of nAChR stimulation on release of radiolabeled NA ([3H]NA). Our data indicate the presence of functional nAChRs on NA terminals in immature cerebellum and subsequent developmental regulation of receptor properties. During postnatal week one, the maximally effective dose of nicotine released 35.0 ± 1.2% of cerebellar [3H]NA stores. There was a subsequent decline in maximal nicotine‐stimulated NA release until postnatal day 30, when Emax values were statistically indistinguishable from adult. Although the efficacy of nicotine changed substantially throughout development, EC50 values did not differ significantly (EC50 = 4.4–12.0 µm). Pharmacological analysis indicated that this developmental shift in maximum nicotine effect reflects a change in the properties of the nAChRs. These data support recent findings of a possible functional role of nAChRs in regulating cerebellar ontogeny, and provides further support for the role of NA as a neurotrophic factor during development.
Effect of experimenter‐delivered and self‐administered cocaine on extracellular β‐endorphin levels in the nucleus accumbens
Authors: Roth‐Deri I. , Zangen A. , Aleli M. , Goelman R. G. , Pelled G. , Nakash R. , Gispan‐Herman I. , Green T. , Shaham Y. , Yadid G. 
Published: March 2003

Abstractβ‐endorphin is an endogenous opioid peptide that has been hypothesized to be involved in the behavioral effects of drugs of abuse including psychostimulants. Using microdialysis, we studied the effect of cocaine on extracellular levels of β‐endorphin in the nucleus accumbens, a brain region involved in the reinforcing effects of psychostimulant drugs. Experimenter‐delivered cocaine (2 mg/kg, i.v.) increased extracellular β‐endorphin immunoreactive levels in the nucleus accumbens, an effect attenuated by 6‐hydroxy‐dopamine lesions or systemic administration of the D1‐like receptor antagonist, SCH‐23390 (0.25 mg/kg, i.p.). The effect of cocaine on β‐endorphin release in the nucleus accumbens was mimicked by a local perfusion of dopamine (5 µm) and was blocked by coadministration of SCH‐23390 (10 µm). Self‐administered cocaine (1 mg/kg/infusion, i.v.) also increased extracellular β‐endorphin levels in the nucleus accumbens. In addition, using functional magnetic resonance imaging, we found that cocaine (1 mg/kg, i.v.) increases regional brain activity in the nucleus accumbens and arcuate nucleus. We demonstrate an increase in β‐endorphin release in the nucleus accumbens following experimenter‐delivered and self‐administered cocaine mediated by the local dopaminergic system. These findings suggest that activation of the β‐endorphin neurons within the arcuate nucleus–nucleus accumbens pathway may be important in the neurobiological mechanisms underlying the behavioral effects of cocaine.
Compounds acting at the endocannabinoid and/or endovanilloid systems reduce hyperkinesia in a rat model of Huntington's disease
Authors: Lastres‐Becker Isabel , De Miguel Rosario , De Petrocellis Luciano , Makriyannis Alexandros , Di Marzo Vincenzo , Fernández‐Ruiz Javier 
Published: March 2003

AbstractWe have recently reported that the administration of AM404, an inhibitor of the endocannabinoid re‐uptake process, which also has affinity for the vanilloid VR1 receptors, is able to reduce hyperkinesia, and causes recovery from neurochemical deficits, in a rat model of Huntington's disease (HD) generated by bilateral intrastriatal injections of 3‐nitropropionic acid (3NP). In the present study, we wanted to explore the mechanism(s) by which AM404 produces its antihyperkinetic effect in 3NP‐lesioned rats by employing several experimental approaches. First, we tried to block the effects of AM404 with selective antagonists for the CB1 or VR1 receptors, i.e. SR141716A and capsazepine, respectively. We found that the reduction caused by AM404 of the increased ambulation exhibited by 3NP‐lesioned rats in the open‐field test was reversed when the animals had been pre‐treated with capsazepine but not with SR141716A, thus suggesting a major role of VR1 receptors in the antihyperkinetic effects of AM404. However, despite the lack of behavioral effects of the CB1 receptor antagonist, the pretreatment with this compound abolished the recovery of neurochemical [γ‐aminobutyric acid (GABA) and dopamine] deficits in the caudate‐ putamen caused by AM404, as also did capsazepine. In a second group of studies, we wanted to explore the potential antihyperkinetic effects of various compounds which, compared to AM404, exhibit more selectivity for either the endovanilloid or the endocannabinoid systems. First, we tested VDM11 or AM374, two selective inhibitors or the endocannabinoid re‐uptake or hydrolysis, respectively. Both compounds were mostly unable to reduce hyperkinesia in 3NP‐lesioned rats, although VDM11 produced a certain motor depression, and AM374 exhibited a trend to stimulate ambulation, in control rats. We also tested the effects of selective direct agonists for VR1 (capsaicin) or CB1 (CP55,940) receptors. Capsaicin exhibited a strong antihyperkinetic activity and, moreover, was able to attenuate the reductions in dopamine and GABA transmission provoked by the 3NP lesion, whereas CP55,940 had also antihyperkinetic activity but was unable to cause recovery of either dopamine or GABA deficits in the basal ganglia. In summary, our data indicate a major role for VR1 receptors, as compared to CB1 receptors, in the antihyperkinetic effects and the recovery of neurochemical deficits caused in 3NP‐lesioned rats by compounds that activate both CB1 and VR1 receptors, either directly or via manipulation of the levels of endogenous agonists.
Promotion of tau phosphorylation by MAP kinase Erk1/2 is accompanied by reduced cholesterol level in detergent‐insoluble membrane fraction in Niemann–Pick C1‐deficient cells
Authors: Sawamura Naoya , Gong Jian‐Sheng , Chang Ta‐Yuan , Yanagisawa Katsuhiko , Michikawa Makoto 
Published: March 2003

AbstractNiemann–Pick type C (NPC) disease is a cholesterol‐storage disease accompanied by neurodegeneration with the formation of neurofibrillary tangles, the major component of which is the hyperphosphorylated tau. Here, we examined the mechanism underlying hyperphosphorylation of tau using mutant Chinese hamster ovary (CHO) cell line defective in NPC1 (CT43) as a tool. Immunoblot analysis revealed that tau was hyperphosphorylated at multiple sites in CT43 cells, but not in their parental cells (25RA) or the wild‐type CHO cells. In CT43 cells, mitogen‐activated protein (MAP) kinase Erk1/2 was activated and the specific MAPK inhibitor, PD98059, attenuated the hyperphosphorylation of tau. The amount of protein phosphatase 2A not bound to microtubules was decreased in CT43 cells. CT43 cells but not 25RA cells were amphotericin B‐resistant, indicating that cholesterol level in the plasma membrane of CT43 is decreased. In addition, the level of cholesterol in the detergent‐insoluble, low‐density membrane (LDM) fraction of CT43 cells was markedly reduced compared with the other two types of CHO cells. As LDM domain plays critical role in signaling pathways, these results suggest that the reduced cholesterol level in LDM domain due to the lack of NPC1 may activate MAPK, which subsequently promotes tau phosphorylation in NPC1‐deficient cells.
Role of NAD(P)H:quinone oxidoreductase in the progression of neuronal cell death in vitro and following cerebral ischaemia in vivo
Authors: Kapinya Krisztian J. , Harms Ulrike , Harms Christoph , Blei Katharina , Katchanov Juri , Dirnagl Ulrich , Hörtnagl Heide 
Published: March 2003

AbstractA direct involvement of the antioxidant enzyme NAD(P)H:quinone oxidoreductase (NQO1) in neuroprotection has not yet been shown. The aim of this study was to examine changes, localization and role of NQO1 after different neuronal injury paradigms. In primary cultures of rat cortex the activity of NQO1 was measured after treatment with ethylcholine aziridinium (AF64A; 40 µm), inducing mainly apoptotic cell death, or oxygen‐glucose deprivation (OGD; 120 min), which combines features of apoptotic and necrotic cell death. After treatment with AF64A a significant NQO1 activation started after 24 h. Sixty minutes after OGD a significant early induction of the enzyme was observed, followed by a second increase 24 h later. Enzyme activity was preferentially localized in glial cells in control and injured cultures, however, expression also occurred in injured neuronal cells. Inhibition of the NQO1 activity by dicoumarol, cibacron blue or chrysin (1–100 nm) protected the cells both after exposure to AF64A or OGD as assessed by the decreased release of lactate dehydrogenase. Comparable results were obtained in vivo using a mouse model of focal cerebral ischaemia. Dicoumarol treatment (30 nmol intracerebroventricular) reduced the infarct volume by 29% (p = 0.005) 48 h after the insult. After chemical induction of NQO1 activity by t‐butylhydroquinone in vitro neuronal damage was exaggerated. Our data suggest that the activity of NQO1 is a deteriorating rather than a protective factor in neuronal cell death.
Oxidative stress‐mediated down‐regulation of bcl‐2 promoter in hippocampal neurons
Authors: Pugazhenthi Subbiah , Nesterova Albina , Jambal Purevsuren , Audesirk Gerald , Kern Marcey , Cabell Leigh , Eves Eva , Rosner Marsha R. , Boxer Linda M. , Reusch Jane E.‐B. 
Published: March 2003

AbstractGeneration of oxidative stress/reactive oxygen species (ROS) is one of the causes of neuronal apoptosis. We have examined the effects of ROS at the transcriptional level in an immortalized hippocampal neuronal cell line (H19‐7) and in rat primary hippocampal neurons. Treatment of H19‐7 cells with hydrogen peroxide (150 µm) resulted in a 40% decrease in Bcl‐2 protein and a parallel decrease in bcl‐2 mRNA levels. H19‐7 cells overexpressing bcl‐2 were found to be resistant to ROS‐induced apoptosis. We had previously shown that bcl‐2 promoter activity is positively regulated by the transcription factor cyclic AMP response element binding protein (CREB) in neurons. In the present study, we demonstrate that ROS decreases the activity of luciferase reporter gene driven by a cyclic AMP response element site containing bcl‐2 promoter. Exposure of neurons to ROS for 6 h resulted in basal and fibroblast growth factor‐2‐stimulated phosphorylation/activation of CREB. Chronic 24 h treatment with ROS led to a significant (p < 0.01) decrease in CREB protein and CREB mRNA levels. Adenoviral overexpression of wild type CREB in H19‐7 cells resulted in significant (p < 0.01) protection against ROS‐induced apoptosis through up‐regulation of Bcl‐2 expression whereas dominant negative CREB exaggerated the injury. These findings demonstrate that loss of CREB function contributes to oxidative stress‐induced neuronal dysfunction.
Gender bias in nursing care? Gender‐related differences in patient satisfaction with the quality of nursing care
Authors: Foss Christina 
Published: March 2003

Gender bias in nursing care? Gender‐related differences in patient satisfaction with the quality of nursing care Gender‐related differences in experience with nursing care, was studied using data from a Norwegian survey of patient‐satisfaction. The survey included 1469 male and 1226 female patients. Results showed that young female patients were less content with all aspects of nursing care when compared with young male patients. Female patients experienced, quite contrary to their male counterparts, that the nursing staff was less committed and caring, has less time and was less skilled. The young women were also less content with what they felt was a lack of opportunity to provide the staff with information they believed to be important to their condition or ailment. Analysis also revealed that female patients, compared with their male counterparts, indicated a higher score on the subjective importance of the different aspects of care. These findings are discussed on the basis of gender‐related research in general. The finding of lower satisfaction amongst younger female patients could be ascribed to the power‐balance between nursing staff and patients. The discussion shows, however, that there are a number of possible interpretations as to why female patients are less content with nursing care compared with male patients. As the reasons for the findings may be derived from several sources it becomes evident that there is a need for further research using alternative approaches.