bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection against dopaminergic nigrostriatal cell death by excitatory input ablation
Authors: Takada M. , Matsumura M. , Kojima J. , Yamaji Y. , Inase M. , Tokuno H. , Nambu A. , Imai H. 
Published: March 2003

AbstractThe importance of enhanced glutamatergic neurotransmission in the basal ganglia and related structures has recently been highlighted in the development of Parkinson's disease. The pedunculopontine tegmental nucleus (PPN) is the major origin of excitatory, glutamatergic input to dopaminergic nigrostriatal neurons of which degeneration is well known to cause Parkinson's disease. Based on the concept that an excitatory mechanism mediated by glutamatergic neurotransmission underlies the pathogenesis of neurodegenerative disorders, we made an attempt to test the hypothesis that removal of the glutamatergic input to the nigrostriatal neurons by PPN lesions might prevent 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced parkinsonism in the macaque monkey. The PPN was lesioned unilaterally with microinjection of kainic acid, and, then, MPTP was administered systemically. In these monkeys, the degree of parkinsonian motor signs was behaviourally evaluated, and the histological changes in the dopaminergic nigrostriatal system were analysed by means of tyrosine hydroxylase immunohistochemistry. The present results revealed that nigrostriatal cell loss and parkinsonian motor deficits were largely attenuated in the MPTP‐treated monkey group whose PPN had been lesioned, compared with the control, MPTP‐treated monkey group with the PPN intact. This clearly indicates that the onset of MPTP neurotoxicity is suppressed or delayed by experimental ablation of the glutamatergic input to the nigrostriatal neurons. Such a protective action of excitatory input ablation against nigrostriatal cell death defines evidence that nigral excitation driven by the PPN may be implicated in the pathophysiology of Parkinson's disease.
Increased rewarding properties of morphine in dopamine‐transporter knockout mice
Authors: Spielewoy Cécile , Gonon François , Roubert Christine , Fauchey Valérie , Jaber Mohamed , Caron Marc G. , Roques Bernard P. , Hamon Michel , Betancur Catalina , Maldonado Rafael , Giros Bruno 
Published: March 2003

AbstractThe activation of dopamine (DA) neurotransmission plays a crucial role in the behavioural responses to drugs of abuse. In particular, increased extracellular levels of DA within the mesolimbic pathway have been implicated in the rewarding and locomotor stimulatory properties of morphine. We investigated the behavioural responses to morphine in mice with a genetic disruption of the DA transporter (DAT), resulting in a constitutively high level of extrasynaptic DA. In the conditioned place preference test, DAT–/– mice exhibited a stronger rewarding response to morphine (5 mg/kg, s.c.) compared with control littermates. However, the same dose of morphine failed to increase locomotor activity in DAT–/– mice, whilst enhancing locomotion in DAT+/– and DAT+/+ animals. Morphine‐induced analgesia was unaffected in mutant mice, but the behavioural expression of naloxone‐induced withdrawal signs was blunted. In vivo voltammetry in the shell of the nucleus accumbens revealed that morphine was able to stimulate DA neurons in DAT–/– mice, resulting in the accumulation of higher extracellular DA levels compared with control animals. Morphine also induced a higher rate of c‐fos transcription in the shell of the nucleus accumbens in mutant mice. We conclude that morphine‐induced rewarding responses are firmly established in DAT mutant mice despite a DA transmission that is already tonically activated, and independently of any effect on locomotion. These particular behavioural responses to morphine may be associated with the action of the drug on DA release and c‐fos expression in the shell of the nucleus accumbens of DAT–/– mice.
Differential amygdala responses to winning and losing: a functional magnetic resonance imaging study in humans
Authors: Zalla Tiziana , Koechlin Etienne , Pietrini Pietro , Basso Gianpaolo , Aquino Patrick , Sirigu Angela , Grafman Jordan 
Published: March 2003

AbstractThe amygdala has been shown to respond to many distinct types of affective stimuli, including reward and punishment feedback in animals. In humans, winning and losing situations can be considered as reward and punishment experiences, respectively. In this study, we used functional magnetic resonance imaging (fMRI) to measure regional brain activity when human subjects were given feedback on their performance during a simple response time task in a fictitious competitive tournament. Lexical stimuli were used to convey positive ‘win’ or negative ‘lose’ feedback. The frequency of positive and negative trials was parametrically varied by the experimenters independently from the subjects' actual performance and unbeknownst to them. The results showed that the parametric increase of winning was associated with left amygdala activation whereas the parametric increase of losing was associated with right amygdala activation. These findings provide functional evidence that the human amygdala differentially responds to changes in magnitude of positive or negative reinforcement conveyed by lexical stimuli.
N‐methyl‐ d‐aspartate enhancement of the glycine response in the rat sacral dorsal commissural neurons
Authors: Le Xu Tian‐. , Dong Xian‐Ping , Wang Dian‐Shi 
Published: March 2003

AbstractThe effect of N‐methyl‐ d‐aspartate (NMDA) on the glycine (Gly) response was examined in neurons acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) using the nystatin‐perforated patch‐recording configuration under voltage‐clamp conditions. The application of 100 μm NMDA to SDCN neurons reversibly potentiated Gly‐activated Cl– currents (IGly) without affecting the Gly binding affinity and the reversal potential of IGly. A selective NMDA receptor antagonist, APV (100 μm), blocked the NMDA‐induced potentiation of IGly, whereas 50 μm CNQX, a non‐NMDA receptor antagonist, did not. The potentiation effect was reduced when NMDA was applied in a Ca2+‐free extracellular solution or in the presence of BAPTA AM, and was independent of the activation of voltage‐dependent Ca2+ channels. Pretreatment with KN‐62, a selective Ca2+–calmodulin‐dependent protein kinase II (CaMKII) inhibitor, abolished the NMDA action. Inhibition of calcineurin (CaN) further enhanced the NMDA‐induced potentiation of IGly. In addition, the GABAA receptor‐mediated currents were suppressed by NMDA receptor activation in the SDCN neurons. The present results show that Ca2+ entry through NMDA receptors modulates the Gly receptor function via coactivation of CaMKII and CaN in the rat SDCN neurons. This interaction may represent one of the important regulatory mechanisms of spinal nociception. The results also suggest that GABAA and Gly receptors may be subject to different intracellular modulatory pathways.
Dopamine‐independent action of cocaine on striatal and accumbal neurons
Authors: Kiyatkin Eugene A. , Rebec George V. 
Published: March 2003

AbstractIncreasing evidence suggests that dopamine (DA) mechanisms alone cannot fully explain the psychoemotional and behavioural effects of cocaine, including its ability to induce drug‐taking behaviour. Although it is known that cocaine, after intravenous administration or smoking, may reach brain levels high enough to inhibit Na+ transport, the role of this action remains unclear. To examine the contribution of local anaesthetic and DA mechanisms to changes in striatal and accumbal neuronal activity induced by cocaine, single‐unit recording was combined with iontophoresis in awake, unrestrained rats. Most spontaneously active and glutamate‐stimulated neurons were highly sensitive to brief cocaine applications (0–40 nA); cocaine‐induced inhibitions occurred at small ejection currents (0–5 nA), were dose‐dependent, highly stable during repeated applications and strongly dependent on basal activity rates. These neuronal responses remained almost unchanged after systemic administration of either a selective D1 antagonist (SCH‐23390, 0.2 mg/kg) or a combination of SCH‐23390 (1 mg/kg) and eticlopride (1 mg/kg), a D2 antagonist. Whereas SCH‐23390 alone had a weak attenuating effect, no effect and even a slight enhancement of responses to cocaine occurred in fast‐firing glutamate (GLU)‐stimulated units after the combined blockade of D1 and D2 receptors. Responses to cocaine were mimicked by iontophoretic procaine (0–40 nA), a short‐acting local anaesthetic with minimal effect on DA uptake. Procaine‐induced inhibitions occurred at the same low currents, had a similar time‐course, and were also strongly dependent on basal discharge rate. Our data support the existence of a DA‐independent mechanism for the action of cocaine involving a direct interaction with Na+ channels. Although further studies are required to clarify this mechanism and its interaction with other pharmacological and behavioural variables, a direct interaction with Na+ channels may contribute to changes in neuronal activity induced by self‐injected cocaine, thereby playing a role in mediating the psychoemotional and behavioural effects of this drug.
Transplanted CNS stem cells form functional synapses in vivo
Authors: Auerbach Jonathan M. , Eiden Maribeth V. , McKay Ron D. G. 
Published: March 2003

AbstractAn understanding of developmental mechanisms and new cell therapies can be achieved by transplantation into the nervous system. Multipotential stem cells have been isolated from the foetal and adult central nervous system (CNS). Immortalized and primary precursor cells integrate into the developing brain generating both neurons and glia as defined by immunological and morphological criteria. Here we show for the first time that in vitro‐expanded CNS precursors, upon transplantation into the brains of rats, form electrically active and functionally connected neurons. These neurons exhibit spontaneous and evoked postsynaptic events and respond to focal glutamate application. Donor cells were grafted into the foetal hippocampus, and the amplitude and frequency of spontaneous synaptic events were monitored in the grafted cells in area CA1 for the first month of postnatal life. The formation of synapses onto grafted neurons indicates that grafted CNS stem cells can be used to study synaptic development in vivo and has important implications for clinical cell replacement therapies.
Influence of the predicted time of stimuli eliciting movements on responses of tonically active neurons in the monkey striatum
Authors: Sardo Pierangelo , Ravel Sabrina , Legallet Eric , Apicella Paul 
Published: March 2003

AbstractChanges in activity of tonically active neurons of the primate striatum are determined both by the behavioural significance of stimuli and the context in which stimuli are presented. We investigated how the responses of these neurons are modified by the temporal predictability of stimuli eliciting learned behavioural reactions. Single neurons were recorded from the caudate nucleus and putamen of two macaque monkeys performing a visual reaction time task under conditions in which the timing of the trigger stimulus was made more or less predictable. The monkeys' ability to predict the trigger onset was assessed by measuring arm movement reaction times and saccadic ocular reactions. Of 171 neurons responding to the unsignalled presentation of the trigger stimulus, 32% lost their response when an instruction cue preceded the trigger by a highly practised 1.5 s interval, and the response reappeared when this interval was varied randomly from 1 to 2.5 s or prolonged to 3 or 4.5 s. Although 43% of the neurons remained responsive irrespective of task condition, the responses were stronger with longer intervals than with the accustomed 1.5 s interval. In addition, a number of neurons responding to the instruction lost their response when the trigger appeared more distant from the instruction. These findings demonstrate that neuronal responses to a movement‐triggering signal become more numerous and pronounced when the degree of temporal predictability of that signal was decreased. We conclude that tonic striatal neurons are sensitive to temporal aspects of stimulus prediction.
The ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by β‐amyloid
Authors: Bastianetto Stéphane , Ramassamy Charles , Doré Sylvain , Christen Yves , Poirier Judes , Quirion Rémi 
Published: March 2003

AbstractSubstantial evidence suggests that the accumulation of β‐amyloid (Aβ)‐derived peptides, and to a lesser extent free radicals, may contribute to the aetiology and/or progression of Alzheimer's disease (AD). Ginkgo biloba extract (EGb 761) is a well‐defined plant extract containing two major groups of constituents, i.e. flavonoids and terpenoids. It is viewed as a polyvalent agent with a possible therapeutic use in the treatment of neurodegenerative diseases of multifactorial origin, e.g. AD. We have investigated here the potential effectiveness of EGb 761 against toxicity induced by (Aβ)‐derived peptides (Aβ25−35, Aβ1−40 and Aβ1−42) on hippocampal primary cultured cells, this area being severely affected in AD. A co‐treatment with EGb 761 concentration‐dependently (10–100 μg/mL) protected hippocampal neurons against toxicity induced by Aβ fragments, with a maximal and complete protection at the highest concentration tested. Similar, albeit less potent protective effects were seen with the flavonoid fraction of the extract (CP 205), while the terpenes were ineffective. Most interestingly, EGb 761 (100 μg/mL) was even able to protect (up to 8 h) hippocampal cells from a pre‐exposure to Aβ25−35 and Aβ1−40. EGb 761 was also able to both protect and rescue hippocampal cells from toxicity induced by H2O2 (50–150 μm), a major peroxide possibly involved in mediating Aβ toxicity. Moreover, EGb 761 (10–100 μg/mL), and to a lesser extent CP 205 (10–50 μg/mL), completely blocked Aβ‐induced events, e.g. reactive oxygen species accumulation and apoptosis. These results suggest that the neuroprotective effects of EGb 761 are partly associated with its antioxidant properties and highlight its possible effectiveness in neurodegenerative diseases, e.g. AD via the inhibition of Aβ‐induced toxicity and cell death.
SEK1/MKK4, c‐Jun and NFΚB are differentially activated in forebrain neurons during postnatal development and injury in both control and p75NGFR‐deficient mice
Authors: Ward Nicole L. , Hagg Theo 
Published: March 2003

AbstractThe common neurotrophin receptor (p75NGFR) can signal in vitro through activation of the c‐Jun N‐terminal kinase (JNK) pathway and nuclear translocation of NFΚB. Activation of JNK and its substrate c‐Jun can lead to apoptosis. We investigated these activities in vivo by comparing immunoreactivity for phosphorylated(p) SEK‐1 (or MKK4, which activates JNK), c‐Jun (ser63, ser73) and nuclear translocation of NFΚB‐p50 in tissue sections through the forebrain of control and p75NGFR‐deficient mice. During postnatal development, SEK1p‐immunoreactivity was detectable in p75NGFR‐positive cholinergic neurons and p75NGFR‐negative neurons throughout the forebrain in control mice. During development, few cells contained c‐Junp, although many neurons contained c‐Jun. No obvious c‐Jun immunostaining was present in the adult forebrain. At any age, NFΚB‐p50 immunoreactivity was seen in nuclei of most cells throughout the forebrain. Following fimbria fornix transection in adult mice, few basal forebrain neurons contained SEK1p while many axotomized choline acetyltransferase (ChAT)‐positive neurons contained c‐Junp and nuclear NFΚB‐p50. The immunostaining patterns of SEK1p, c‐Junp and NFKB during development and following injury were largely similar in p75NGFR‐deficient mice. During development, cells throughout the forebrain had TdT‐mediated dUTP‐biotin nick end labelling (TUNEL)‐labelling (a potential marker for apoptosis), however, their presence was not predicted by number of neurons stained for SEK1p or c‐Junp. These results suggest that the expected activation of the JNK pathway by p75NGFR, as well as the expected relationship between SEK1 and downstream activation of c‐Jun do not occur in the mammalian forebrain. Also, these results suggest that this activation does not necessarily lead to cell death.
Expression of Fos‐related antigens in the nucleus accumbens and associated regions following exposure to a cocaine‐paired environment
Authors: Franklin Teresa R. , Druhan Jonathan P. 
Published: March 2003

AbstractThis study examined whether conditioned hyperactivity measured in a cocaine‐paired environment was associated with increased expression of Fos‐related antigens (FRA) within the nucleus accumbens (NAc) and associated forebrain regions of rats. Three groups of rats were given repeated injections of either cocaine in the test environment and saline in the colony room (group Paired), saline in the test environment and cocaine in the colony room (group Unpaired), or saline in both environments (group Control). All rats were subsequently given a drug‐free test for conditioned hyperactivity in the test environment, and their brains were removed so that FRA immunohistochemistry could be conducted. Rats in the Paired group showed conditioned hyperactivity during the conditioning test, and this behavioural response was associated with increased FRA expression within the caudal NAc, the medial prefrontal cortex and the lateral septum relative to the Unpaired and Control groups. Paired rats also showed increased FRA expression within the orbital prefrontal cortex, the claustrum, the caudal amygdala (basolateral and central regions), the paraventricular thalamic nucleus, the subiculum of the hippocampus, and the lateral habenula relative to the Control group. However, the FRA levels in these latter sites were not significantly increased relative to those of Unpaired rats, indicating that genomic responses in these regions were not entirely context dependent. The correspondence between conditioned hyperactivity and enhanced FRA expression within the caudal NAc, the medial prefrontal cortex and lateral septum suggests that these regions may participate in the expression of conditioned responses to cocaine‐related stimuli.
Depolarization‐dependent survival of cultured mouse cerebellar granule neurons is strain‐restrained
Authors: Fujikawa Naoto , Tominaga‐Yoshino Keiko , Okabe Masaru , Ogura Akihiko 
Published: March 2003

AbstractCerebellar granule neurons (CGNs) isolated from the rat are often used as a model system for the analysis of activity‐dependent survival of neurons. These cells do not survive in culture without addition of a depolarizing agent (KCl or glutamate) to the medium. However, it has been reported that mouse CGN behave differently. Here we found that the requirement for depolarization for the survival of the mouse CGN was strain‐dependent, which may be important for future analyses using transgenic animals. CGNs from the Balb/C mouse could survive without KCl addition, whereas CGNs from the C57Bl/6 mouse could not (similar to the rat CGN). The survival‐promoting activity of the Balb/C mouse CGNs was transferable by coculturing. However, the medium of the Balb/C mouse CGN culture was ineffective, suggesting that the neurotrophic substance that is supposed to be released is labile. Although we are yet to specify the substance, it might be independent of neurotrophins. It is necessary to select the strain of mouse in the production of transgenic animals for the analyses of activity‐dependent neuronal survival.
X‐ray kinematic analysis of forelimb movements during target reaching and food taking in the cat
Authors: Boczek‐Funcke A. , Kuhtz‐Buschbeck J. ‐P. , Paschmeyer B. , Illert M. 
Published: March 2003

AbstractWe have used a three‐dimensional X‐ray cinematographic approach to investigate the kinematics of the forelimb during target reaching and food taking in five cats. Measurements of the trajectory of the limb during the reaching movement showed that the movement paths of the metacarpophalangeal joint (MCP) and the wrist were sigmoidal with a long nearly linear segment. The elbow followed a bent movement path with maximal inflection in the middle. The path of the humerus had an ascending parabola‐like characteristic. The velocity profiles of the MCP and wrist were nearly bell‐shaped and skewed to the left, whereas the profiles of the elbow joint were more or less double peaked with the second peak occurring 60–40 ms before object contact. Several different velocity peaks reflecting specific aspects of the task existed when the bell‐shaped velocity profiles were divided in their vectorial components. Angular motion of the elbow consisted of a flexion–extension sequence during the reach and a flexion during the subsequent retraction. After an initial flexion during lift‐off the wrist was extended. It kept this extended position during orienting towards the food container. During the retraction phase it was further extended. The angle between the wrist axis and the parasagittal plane changed during the movement. It first increased, then decreased during the last 100 ms before the object was reached. During the retraction it increased again to support the object weight against gravity. The position of the wrist was established by radio‐ulnar supination and movements of the whole arm around the shoulder joint. We hypothesize that the position of the wrist axis is the controlled variable during protraction and retraction, regardless of whether it is achieved by radio‐ulnar supination or by movements around the shoulder.
Reciprocal actions of interleukin‐6 and brain‐derived neurotrophic factor on rat and mouse primary sensory neurons
Authors: Murphy P. G. , Borthwick L. A. , Altares M. , Gauldie J. , Kaplan D. , Richardson P. M. 
Published: March 2003

AbstractIn low‐density, serum‐free cultures of neurons from embryonic rat dorsal root ganglia, interleukin‐6 supports the survival of less than one third of the neurons yet virtually all of them bear interleukin‐6 α‐receptors. A finding that might explain this selectivity is that interleukin‐6 acts on sensory neurons in culture through a mechanism requiring endogenous brain‐derived neurotrophic factor. Antibodies or a trkB fusion protein that block the biological activity of brain‐derived neurotrophic factor synthesized by dorsal root ganglion neurons also block the survival‐promoting actions of interleukin‐6 on these neurons. Two results indicate that interleukin‐6 influences synthesis of brain‐derived neurotrophic factor in adult dorsal root ganglion neurons. Intrathecal infusion of interleukin‐6 in rats increases the concentration of brain‐derived neurotrophic factor mRNA in rat lumbar dorsal root ganglia. The induction of brain‐derived neurotrophic factor in dorsal root ganglion neurons that is seen after nerve injury in rats or wild‐type mice is severely attenuated in mice with null mutation of the interleukin‐6 gene. In brief, the ability of interleukin‐6 to support the survival of embryonic sensory neurons in vitro depends upon the presence of endogenous brain‐derived neurotrophic factor and the induction of brain‐derived neurotrophic factor in injured adult sensory neurons depends upon the presence of endogenous interleukin‐6.