bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cocaine‐induced psychomotor activity is associated with its ability to induce c‐fos mRNA expression in the subthalamic nucleus: effects of dose and repeated treatment
Authors: Uslaner Jason M. , Crombag Hans S. , Ferguson Susan M. , Robinson Terry E. 
Published: May 2003

AbstractFactors that modulate the psychomotor activating effects of amphetamine and cocaine, such as environmental novelty and dose, also regulate the ability of these drugs to induce c‐fos mRNA expression in the subthalamic nucleus (STN). We hypothesized therefore that engagement of the STN may be important for stimulant‐induced psychomotor activation. To further test this hypothesis we examined whether repeated treatment with cocaine, which enhances its psychomotor activating effects (i.e. produces behavioural sensitization), also enhances its ability to induce c‐fos expression in the STN. In addition, given that STN activity is thought to be influenced by preproenkephalin mRNA‐containing (ENK+) neurons in the caudate–putamen, we also examined whether repeated cocaine treatment alters c‐fos expression in ENK+ cells. We report that: (i) cocaine pretreatment enhances the ability of a cocaine challenge to induce c‐fos mRNA expression in the STN, and this effect is most robust at challenge doses where behavioural sensitization is observed; (ii) the ability of cocaine to induce c‐fos in the STN is independent of the ability of cocaine to engage ENK+ cells. These results support the idea that the STN is involved in stimulant‐induced psychomotor activation and sensitization, but suggest that stimulant‐induced engagement of the STN is not dependent on ENK+ cells in the caudate–putamen. These findings may have implications concerning the neurobiological mechanisms underlying the behavioural effects of psychostimulant drugs.
D‐2‐hydroxyglutaric acid induces oxidative stress in cerebral cortex of young rats
Authors: Latini Alexandra , Scussiato Karina , Rosa Rafael Borba , Llesuy Susana , Belló‐Klein Adriane , Dutra‐Filho Carlos Severo , Wajner Moacir 
Published: May 2003

AbstractLarge amounts of d‐2‐hydroxyglutaric acid (DGA) accumulate in d‐2‐hydroxyglutaric aciduria (D‐2‐OHGA), an inherited neurometabolic disorder characterized by severe neurological dysfunction and cerebral atrophy. Despite the significant brain abnormalities, the neurotoxic mechanisms of brain injury in this disease are virtually unknown. In this work, the in vitro effect of DGA on various parameters of oxidative stress was investigated; namely chemiluminescence, thiobarbituric acid‐reactive substances (TBA‐RS), total radical‐trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR) and the activities of the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase in cerebral cortex from 30‐day‐old‐rats. DGA significantly increased chemiluminescence and TBA‐RS and decreased TAR values in the cortical supernatants. In contrast, TRAP and the antioxidant enzyme activities were not altered by the metabolite. Furthermore, the DGA‐induced increase of TBA‐RS was fully prevented by the free radical scavengers ascorbic acid plus Trolox (water‐soluble α‐tocopherol) and attenuated by the inhibitor of nitric oxide synthase Nω‐nitro‐L‐arginine methyl ester (L‐NAME), suggesting the role of superoxide, hydroxyl and nitric oxide radicals in this action. The data indicate a stimulation of lipid peroxidation through the production of free radicals and a reduction of the brain capacity to efficiently modulate the damage associated with the enhanced generation of free radicals by DGA. In the case that these findings also occur in human D‐2‐OHGA, it is feasible that oxidative stress may be involved in the pathophysiology of the brain injury observed in patients with this disease.
Insulin‐like growth factor‐I as a promoting factor for cerebellar Purkinje cell development
Authors: Fukudome Yuko , Tabata Toshihide , Miyoshi Tomoko , Haruki Shigeki , Araishi Kenji , Sawada Satsuki , Kano Masanobu 
Published: May 2003

AbstractIn the mammalian CNS, the peptide hormone insulin‐like growth factor‐I (IGF‐I) is synthesized in a certain subset of neurons and, it has been suggested, serves as a local neurotrophic factor. A postnatal increase in the expression of IGF‐I and the type‐1 IGF receptors (IGFR1) in the cerebellar cortex and its related brain regions indicates that developing cerebellar Purkinje cells (PC) may be an important target of IGF‐I. However, little is known about how IGF‐I influences PC development. Here we addressed this question, using a reduced environment of cerebellar neuron culture derived from perinatal mice. IGF‐I exogenously applied at a physiological concentration (10 nm) greatly promoted the dendritic growth and survival of the PCs. By contrast, IGF‐I only slightly promoted the somatic growth and little affected the maturation of the electrophysiological excitability of the PCs. The closely related hormone insulin had weaker promoting effects than did IGF‐I. IGF‐I appeared to at least bind to IGFR1 and to up‐regulate the signalling pathways involving the phosphoinositide 3‐kinase (PI3‐K), mitogen‐activated protein kinase (MAPK), p38 kinase (p38K), and an unknown signalling molecule(s). These signalling pathways may be coupled to the individual aspects of PC development in different manners and this may explain the difference in effects of IGF‐I among these aspects. These findings suggest that IGF‐I serves as a promoting factor for PC development, particularly postnatal survival and dendritic growth.
Alterations in the intrauterine environment by glucocorticoids modifies the developmental programme of the auditory system
Authors: Canlon Barbara , Erichsen Susan , Nemlander Elin , Chen Ming , Hossain Amzad , Celsi Gianni , Ceccatelli Sandra 
Published: May 2003

AbstractPrenatal exposure to excessive glucocorticoids alters the programming of the metabolic and endocrine balance of various organs, including the nervous system. In the present study, prenatal glucocorticoid treatment was shown to increase the susceptibility of the inner ear to acoustic noise trauma in adult life. Acute auditory brainstem response thresholds were not different between the age‐matched groups. However, when measured at 48 h and 4 weeks postexposure, the dexamethasone (DEX)‐treated rats showed little or no recovery from the trauma. In contrast, normal rats showed a significant amount of recovery by 48 h postexposure and continued to show further recovery over 4 weeks. In addition, acoustic trauma resulted in a massive outer hair cell loss in the DEX rats compared to minor loss in the normal rats. To determine whether oxidative stress plays a role in the recovery phase of acoustic trauma, the free radical scavenger PBN (100 mg/kg) was administered before, during and several times after noise exposure. PBN treatment significantly reduced the physiological and morphological cochlear differences which were observed between DEX and control rats after acoustic trauma. These data support the hypothesis that alterations in the intrauterine environment may modify the developmental programme of the cochlea, inducing dysfunction later in adult life. Excessive prenatal exposure to dexamethasone decreased the potential for recovery of the cochlea to oxidative stress induced by acoustic trauma; this decreased recovery potential can be counteracted by treatment with antioxidants.
Glutamate motivational ensembles in nucleus accumbens: rostrocaudal shell gradients of fear and feeding
Authors: Reynolds Sheila M. , Berridge Kent C. 
Published: May 2003

AbstractThis study demonstrates that microinjection of an AMPA/kainate glutamate antagonist elicits motivated fear and feeding behaviour mapped along rostrocaudal gradients of positive‐to‐negative valence in nucleus accumbens shell (similar to rostrocaudal shell gradients recently reported for GABA agonist microinjections). Rats received rostral or caudal microinjections of the glutamate AMPA/kainate receptor antagonist DNQX (0, 50, 450 or 850 ng in 0.5 µL) or the NMDA receptor antagonist MK‐801 (0, 0.5, 1 or 2 µg in 0.5 µL), into medial accumbens shell prior to behavioural tests for fear, feeding or conditioning of place preference or avoidance. Another group received rostral or caudal microinjections of DNQX in nucleus accumbens core. Rostral shell DNQX microinjections potently increased appetitive food intake and established only weak conditioned place avoidance. Caudal shell DNQX microinjections elicited defensive treading behaviour, caused rats to defensively bite the experimenter and emit fearful distress vocalizations when handled, and established strong conditioned place avoidance. By contrast, no rostrocaudal gradients of motivational bivalence were produced by microinjections of the glutamate AMPA/kainate receptor antagonist DNQX into the core, or by microinjections of the NMDA antagonist MK‐801 into the shell. Our results indicate that appetitive and aversive motivation is carried in anatomically differentiated channels by mesocorticolimbic glutamate signals to microcircuits in the medial shell. Hyperpolarization of local shell ensembles by AMPA/kainate glutamate receptor blockade elicits fear and feeding behaviours mapped along distinct positive‐to‐negative rostrocaudal gradients.
Two distinct calcium‐sensitive and ‐insensitive PKC up‐ and down‐regulate an α‐bungarotoxin‐resistant nAChR1 in insect neurosecretory cells (DUM neurons)
Authors: Courjaret Raphaël , Grolleau Françoise , Lapied Bruno 
Published: May 2003

AbstractWhile there is mounting knowledge about the structure and diversity of insect neuronal nicotinic acetylcholine receptors, less attention has been directed towards their intracellular regulation by calcium‐mediated activation or inhibition of protein phosphorylation. The main goal of this work was to delineate the chain of molecular events that lead to the up‐ and down‐regulation by two protein kinase Cs of an insect neuronal α‐bungarotoxin‐resistant nicotinic acetylcholine receptor (called nAChR1). The native nicotinic acetylcholine receptor intracellular regulation was studied on dissociated adult dorsal unpaired median neurons isolated from the terminal abdominal ganglion of the cockroach Periplaneta americana using whole‐cell patch‐clamp technique and calcium imaging. We report that under 0.5 µmα‐bungarotoxin treatment, the inward current produced by pressure ejection application of nicotine onto the cell body was differentially sensitive to specific protein kinase C activators and inhibitors. The phorbol ester PMA produced a calcium‐dependent increase in current amplitude blocked by chelerythrine. By contrast, the diacylglycerol analogue 1,2‐dioctanoyl‐sn‐glycerol produced a calcium‐independent reduction of the nicotinic response, reversed by rottlerin and chelerythrine. This indicated that two protein kinase C isozymes (‘classical’ and ‘novel’ protein kinase C, named PKC1 and PKC2, respectively) up‐ and down‐regulated nicotinic acetylcholine receptor function. PMA and 1,2‐dioctanoyl‐sn‐glycerol effects were mimicked by pirenzepine‐sensitive M1 muscarinic receptor subtype coupled to phospholipase C second messenger pathway. Low concentration of muscarine elevated internal calcium levels, which thereby activated PKC1. By contrast, a high concentration of muscarine strongly increased [Ca 2+]i, which induced inhibition of PKC1. This effect was reversed by FK506, suggesting the implication of PP2B which unmasked PKC2 activity mediating down‐regulation of nicotinic acetylcholine receptor.
Characterization of the human visual V6 complex by functional magnetic resonance imaging
Authors: Dechent Peter , Frahm Jens 
Published: May 2003

AbstractMagnetoencephalography of a visual area along the human parieto‐occipital sulcus suggested that this region represents the human homologue of the monkey visual area V6 complex (visual area V6/visuomotor area V6A) involved in the integration of visual and somatomotor information. We used functional magnetic resonance imaging at 2.0 T and 2 × 2 × 3 mm3 resolution (16 sections) to characterize visual areas along the parieto‐occipital sulcus in five healthy human subjects. Paradigms comprised a full‐field checkerboard stimulation, a full‐field luminance flicker as well as a foveal and peripheral luminance flicker using both a direct and differential design for comparing functional states. Along the parieto‐occipital sulcus, and in contrast to primary visual areas, luminance stimulation evoked much larger activation volumes than checkerboard stimulation. Moreover, based on anatomic landmarks, luminance stimulation identified two functionally distinct regions of parieto‐occipital sulcus activations: an inferior part (supposedly visual area V6) and a superior portion (supposedly visuomotor area V6A). With these assignments, foveal vs. peripheral luminance stimulation revealed a weaker foveal overrepresentation in visual area V6/visuomotor area V6A than in early visual areas, and only a mild tendency for a retinotopic organization in visual area V6. Further analyses of the functional coding of the human visual area V6 complex require functional magnetic resonance imaging at even higher spatial resolution.
Neonatal administration of monosodium glutamate prevents the development of ethanol‐ but not psychostimulant‐induced sensitization: a putative role of the arcuate nucleus
Authors: Miquel Marta , Font Laura , Sanchis‐Segura Carles , Aragon Carlos M.G. 
Published: May 2003

AbstractLesions of the arcuate nucleus by monosodium glutamate, goldthioglucose and oestradiol valerate treatments are known to prevent the acute stimulating effect of ethanol in mice. On the basis of these results, the current study analysed whether a lesion of the arcuate nucleus by monosodium glutamate was able to block ethanol‐induced locomotor sensitization. To produce the arcuate nucleus lesions, pups were injected with saline or monosodium glutamate (4 mg/g body weight) subcutaneously on 5 alternate days, starting on postnatal day one. Sensitization treatments began 10 weeks after the initial lesions. Sensitization training consisted of six trials on alternate days, in which groups of mice were treated with ethanol (2 g/kg) or saline, and then tested in an open‐field for the induction of locomotor activity. The present study demonstrated that animals with monosodium glutamate‐induced lesions did not develop locomotor sensitization to ethanol. Different groups of mice were used to assay blood ethanol levels and to evaluate the effect of arcuate nucleus lesions on psychostimulant‐induced locomotor sensitization. Sensitization to cocaine or amphetamine was spared in monosodium glutamate‐pre‐treated animals, although the lesion of arcuate nucleus reduced the sensitivity of mice to cocaine. Our findings therefore suggest that the arcuate nucleus may be critical for the neuroadaptations that underlie the behavioural sensitization to ethanol, in contrast to those mediating psychostimulant‐induced sensitization.
Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis
Authors: Brown Jason , Cooper‐Kuhn Christiana M. , Kempermann Gerd , Van Praag Henriette , Winkler Jürgen , Gage Fred H. , Kuhn H. Georg 
Published: May 2003

AbstractExposure to an enriched environment and physical activity, such as voluntary running, increases neurogenesis of granule cells in the dentate gyrus of adult mice. These stimuli are also known to improve performance in hippocampus‐dependent learning tasks, but it is unclear whether their effects on neurogenesis are exclusive to the hippocampal formation. In this study, we housed adult mice under three conditions (enriched environment, voluntary wheel running and standard housing), and analysed proliferation in the lateral ventricle wall and granule cell neurogenesis in the olfactory bulb in comparison to the dentate gyrus. Using bromodeoxyuridine to label dividing cells, we could not detect any difference in the number of newly generated cells in the ventricle wall. When giving the new cells time to migrate and differentiate in the olfactory bulb, we observed no changes in the number of adult‐generated olfactory granule cells; however, voluntary running and enrichment produced a doubling in the amount of new hippocampal granule cells. The discrepancy between the olfactory bulb and the dentate gyrus suggests that these living conditions trigger locally through an as yet unidentified mechanism specific to neurogenic signals in the dentate gyrus.
Metabotropic glutamate receptor 5 (mGluR5)‐mediated phosphoinositide hydrolysis and NMDA‐potentiating effects are blunted in the striatum of aged rats: a possible additional mechanism in striatal senescence
Authors: Domenici Maria Rosaria , Pintor Annita , Potenza Rosa Luisa , Gaudi Simona , Grò Maria Cristina , Passarelli Francesca , Reggio Rosaria , Galluzzo Mariangela , Massotti Marino , Popoli Patrizia 
Published: May 2003

AbstractThe aim of the present work was to verify whether an impairment of subtype 5 metabotropic glutamate receptor‐mediated neurotransmission did occur in the aged striatum. To this end, the ability of the subtype 5 metabotropic glutamate receptor agonist, RS‐2‐chloro‐5‐hydroxyphenylglycine, to stimulate phosphoinositide hydrolysis and to potentiate N‐methyl‐d‐aspartate‐induced effects in striatal slices from young (3 months) and aged (24 months) rats was compared. The ability of RS‐2‐chloro‐5‐hydroxyphenylglycine to induce maximal phosphoinositide turnover and to potentiate N‐methyl‐d‐aspartate effects was significantly reduced in slices from old vs. young rats. These changes were associated with a significant reduction in the expression of subtype 5 metabotropic glutamate receptor protein (−28.8%) and phospholipase C‐β1 (−55.8%) in old striata, while receptor messenger ribonucleic acid expression was unchanged. These results show that the signalling associated with subtype 5 metabotropic glutamate receptors undergoes significant age‐related changes and that a reduced expression of subtype 5 metabotropic glutamate receptors and, more importantly, phospholipase C‐β1 may account for the functional decline of subtype 5 metabotropic glutamate receptors.
Differential effect of dopamine deficiency on the expression of NMDA receptor subunits in the weaver mouse brain
Authors: Fragioudaki K. , Kouvelas E. D. , Mitsacos A. 
Published: May 2003

AbstractThe weaver mutant mouse is characterized by degeneration of the dopaminergic mesencephalic neurons. The role of the dopaminergic system in the regulation of N‐methyl‐d‐aspartate (NMDA) receptor subunit expression was addressed in the present study. In situ hybridization experiments were conducted to determine the expression levels of the NMDA receptor subunit mRNAs, z1, ε1 and ε2, in striatum, nucleus accumbens, olfactory tubercle and cerebral cortical regions of 26‐day‐, 3‐ and 6‐month‐old weaver mice. Data indicated statistically significant increases in z1 and ε2 mRNA levels in 6‐month‐old weaver striatum, whereas at the same age ε1 mRNA expression was decreased in all striatal regions, as well as in the cortex. In the 26‐day‐old weaver striatum and nucleus accumbens, statistically significant increases were observed in ε1 mRNA levels, whereas no changes were observed in the other two subunits. In the somatosensory cortex of 26‐day‐old weaver brain an increased expression of all three subunits was observed. The upregulation of NMDA receptor subunit expression observed in the somatosensory cortex can be attributed to a decreased activity of the glutamatergic thalamocortical pathway, following the degeneration of the nigrostriatal dopaminergic fibres. In the striatum, the present results demonstrate a differential control on the expression of z1 and ε2 subunits on the one hand, and ε1 subunit on the other. It is suggested that dopamine exerts a negative control on the expression of z1 and ε2 subunits, through a downregulation of transcription factors associated with the AP1 regulatory site, which is mediated by the activation of striatal dopamine D2 receptors.
Diazepam‐induced changes on sleep and the EEG spectrum in mice: role of the α3‐GABAA receptor subtype
Authors: Kopp C. , Rudolph U. , Keist R. , Tobler I. 
Published: May 2003

AbstractBenzodiazepines reduce EEG slow‐wave activity in non‐REM sleep by potentiating GABAergic neurotransmission at GABAA receptors via a modulatory binding site. However, the mechanisms of action underlying the effects of benzodiazepines on sleep and the sleep EEG are still unknown. Slow waves during sleep are generated by the corticothalamic system and synchronized by the inhibitory GABAergic neurons of the reticular thalamic nucleus. This region contains exclusively α3‐containing GABAA receptors. We investigated the role of these receptors in the mediation of diazepam effects on the sleep EEG by studying point‐mutated mice in which the α3‐GABAA receptor is diazepam‐insensitive [α3(H126R)]. Sleep was recorded for 12 h after i.p. injection of 3 mg/kg diazepam or vehicle at light onset in α3(H126R) and wild‐type controls (n = 13–17 per genotype). The main effect was a marked reduction of slow‐wave activity (EEG power density in 0.75–4.00 Hz) in non‐REM sleep and a concomitant increase in frequencies above 15.00 Hz in non‐REM sleep and waking in both genotypes. Neither effect of diazepam differed significantly between the genotypes. Despite the exclusive expression of α3‐containing GABAA receptors in the reticular thalamic nucleus, these receptors do not seem to be critical for the mediation of the effects of diazepam on the sleep EEG.
Formation of a tumour necrosis factor receptor 1 molecular scaffolding complex and activation of apoptosis signal‐regulating kinase 1 during seizure‐induced neuronal death
Authors: Shinoda Sachiko , Skradski Shana L. , Araki Tomohiro , Schindler Clara K. , Meller Robert , Lan Jing‐Quan , Taki Waro , Simon Roger P. , Henshall David C. 
Published: May 2003

AbstractThe consequences of activation of tumour necrosis factor receptor 1 (TNFR1) during neuronal injury remain controversial. The apoptosis signal‐regulating kinase 1 (ASK1), a mitogen‐activated protein kinase kinase kinase, can mediate cell death downstream of TNFR1. Presently, we examined the formation of the TNFR1 signalling cascade and response of ASK1 during seizure‐induced neuronal death. Brief (40 min) seizures were induced in rats by intra‐amygdala microinjection of kainic acid, which elicited unilateral hippocampal CA3 neuronal death. Seizures caused a rapid decline in the expression of the silencer of death domains protein within injured CA3. Co‐immunoprecipitation analysis revealed a commensurate assembly of a TNFR1 scaffold complex containing TNFR‐associated death domain protein, receptor interacting protein and TNFR‐activating factor 2. In addition, recruitment of TNFR‐activating factor 2 was likely promoted by Bcl10‐mediated sequestering of cellular inhibitor of apoptosis protein 2. Apoptosis signal‐regulating kinase 1 was sequestered in a complex that contained the molecular chaperone 14‐3‐3β and protein phosphatase 5. Seizures triggered its dissociation, and the phosphorylation of the ASK1 substrates, mitogen‐activated protein kinase kinase 3/6 and 4. Subsequently, protein phosphatase 5 translocated into the nuclei of degenerating CA3 neurons, while ASK1 colocalized with the adaptor proteins Daxx and TNFR‐activating factor 2 at the outer membrane of injured CA3 neurons. Neutralizing antibodies to TNFα reduced the numbers of DNA damaged cells within the injured hippocampus. These data suggest ASK1 may be involved in the mechanism of seizure‐induced neuronal death downstream of a TNFR1 death‐signalling complex.