bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear localization of N‐terminal mutant huntingtin is cell cycle dependent
Authors: Martín‐Aparicio Ester , Avila Jesús , Lucas José J. 
Published: March 2003

AbstractUnlike normal huntingtin (htt) which is located predominantly in the cytoplasm, mutant htt is also found in the nucleus of affected neurons. Nuclear localization of toxic polyglutamine‐containing proteins has been postulated to be necessary for the pathogenesis of triplet repeat disorders. However, little is known about the mechanism by which mutant htt enters the nucleus. We have recently reported exclusive nuclear localization of exon 1 mutant htt in striatal primary neuronal cultures from the HD94 conditional mouse model of HD. This seemed to contradict the predominant cytoplasmic localization of N‐terminal htt reported from transfection experiments and prompted us to hypothesize that subcellular localization of the toxic htt fragment might be favoured in nondividing cells. To test this, we analyzed subcellular localization of mutant htt in HD94 mixed neuron‐glia cultures. Subconfluent glial cells showed cytoplasmic localization. However, nuclear localization was prompted by confluence, by serum withdrawal, and by treatment with cell cycle progression inhibitors such as Ara C or lactacystin. BrdU labelling experiments further confirmed that nuclear localization does not occur in dividing cells. Our findings offer an explanation for the neuronal specific toxicity of mutant htt despite its ubiquitous expression. Unraveling the mechanism of this cell cycle arrest‐dependent entrance into the nucleus may offer new opportunities for therapeutic intervention.
Electromyographic activity associated with spontaneous functional recovery after spinal cord injury in rats
Authors: Kaegi Sibille , Schwab Martin E. , Dietz Volker , Fouad Karim 
Published: March 2003

AbstractThis investigation was designed to study the spontaneous functional recovery of adult rats with incomplete spinal cord injury (SCI) at thoracic level during a time course of 2 weeks. Daily testing sessions included open field locomotor examination and electromyographic (EMG) recordings from a knee extensor (vastus lateralis, VL) and an ankle flexor muscle (tibialis anterior, TA) in the hindlimbs of treadmill walking rats. The BBB score (a locomotor score named after Bassoet al., 1995,J. Neurotrauma,12, 1–21) and various measures from EMG recordings were analysed (i.e. step cycle duration, rhythmicity of limb movements, flexor and extensor burst duration, EMG amplitude, root‐mean‐square, activity overlap between flexor and extensor muscles and hindlimb coupling). Directly after SCI, a marked drop in locomotor ability occurred in all rats with subsequent partial recovery over 14 days. The recovery was most pronounced during the first week. Significant changes were noted in the recovery of almost all analysed EMG measures. Within the 14 days of recovery, many of these measures approached control levels. Persistent abnormalities included a prolonged flexor burst and increased activity overlap between flexor and extensor muscles. Activity overlap between flexor and extensor muscles might be directly caused by altered descending input or by maladaptation of central pattern generating networks and/or sensory feedback.
Regenerative and survival capabilities of Purkinje cells overexpressing c‐Jun
Authors: Carulli Daniela , Buffo Annalisa , Botta Cristina , Altruda Fiorella , Strata Piergiorgio 
Published: March 2003

AbstractFollowing axotomy, cerebellar Purkinje cells (PCs) do not elongate their axons, even in a favourable environment, and are resistant to death. They have no constitutive presence of common growth‐associated proteins, such as GAP‐43 and c‐Jun Previous experiments show that injured transgenic PCs overexpressing GAP‐43 exhibit a profuse sprouting along the axon and at its severed end. Nevertheless, the lesioned axons are unable to regenerate either spontaneously or into growth‐permissive environments. In addition, a considerable number of GAP‐43 transgenic PCs degenerate after injury. c‐Jun is an inducible transcription factor expressed in axotomized central neurons and regenerating peripheral neurons. It also contributes to programmed cell death during development. To test whether c‐Jun could modify the response of PCs to axotomy or enhance the growth/death phenomena of GAP‐43 Purkinje neurons, we generated transgenic mice overexpressing c‐Jun in PCs. However, c‐Jun upregulation did not affect the adult intact phenotype of these neurons and their regenerative and survival capabilities after axotomy. Also in the cross‐bred GAP‐43/c‐Jun mice, c‐Jun did not modify the response of GAP‐43 PCs to axotomy. By contrast, in organotypic cultures of cerebellum taken from 9‐day‐old‐pups, the survival capabilities of PCs overexpressing c‐Jun decreased, in association with a consistent c‐Jun phosphorylation. On the whole our data show that c‐Jun alone is unable to trigger regenerative or degenerative phenomena in PCs and suggest that the cellular action of this early gene in developing and mature neurons strongly depends on interplaying intracellular signals.
SHORT COMMUNICATION Sodium channel β1‐subunit expression is increased in reactive astrocytes in a rat model for mesial temporal lobe epilepsy
Authors: Gorter Jan A. , Van Vliet Erwin A. , Da Silva Fernando H. Lopes , Isom Lori L. , Aronica Eleonora 
Published: March 2003

AbstractAs several epilepsy syndromes are associated with changes in sodium channel subunits we investigated the expression of β1 sodium channel protein in a rat epilepsy model. In this model a chronic epileptic syndrome develops after electrically induced status epilepticus (SE). Many neuropathological characteristics of mesial temporal lobe epilepsy can be reproduced (cell loss, gliosis and synaptic reorganization). In control hippocampus β1 subunit protein was moderately expressed in neurons and weakly expressed in resting astrocytes. β1 sodium channel immunoreactivity increased markedly within 1 week after SE mainly in astrocytes that were colocalized with vimentin (marker for reactive astrocytes). This up‐regulation was still present in reactive astrocytes of chronic epileptic rats (> 3 months after SE). Considering the fact that the β1 subunits may function as cell adhesion molecules interacting with extracellular matrix, the observed increase in reactive astrocytes might subserve a function in cellular and synaptic reorganization during epileptogenesis.
The functional properties of the human ether‐à‐go‐go‐like (HELK2) K+ channel
Authors: Becchetti Andrea , De Fusco Maurizio , Crociani Olivia , Cherubini Alessia , Restano‐Cassulini Rita , Lecchi Marzia , Masi Alessio , Arcangeli Annarosa , Casari Giorgio , Wanke Enzo 
Published: March 2003

AbstractThe voltage‐dependent K+ channels belonging to the ether‐à‐go‐go family (eag, erg, elk) are widely expressed in the mammalian CNS. Their neuronal function, however, is poorly understood. Among the elk clones, elk2 is the most abundantly expressed in the brain. We have characterized the human ELK2 channel (HELK2) expressed in mammalian cell lines. Moreover, we have detected helk2 mRNA and ELK2‐like currents in freshly dissociated human astrocytoma cells. HELK2 was inhibited by Cs+ in a voltage‐dependent way (Kd was 0.7 mm, at −120 mV). It was not affected by Way 123398 (5 µm), dofetilide (10 µm), quinidine (10 µm), verapamil (20 µm), haloperidol (2 µm), astemizole (1 µm), terfenadine (1 µm) and hydroxyzine (30 µm), compounds known to inhibit the biophysically related HERG channel. The crossover of the activation and inactivation curves produced a steady state ‘window’ current with a peak around −20 mV and considerably broader than it usually is in voltage‐dependent channels, including HERG. Similar features were observed in the ELK2 clone from rat, in the same experimental conditions. Thus, ELK2 channels are active within a wide range of membrane potentials, both sub‐ and suprathreshold. Moreover, the kinetics of channel deactivation and removal of inactivation was about one order of magnitude quicker in HELK2, compared to HERG. Overall, these properties suggest that ELK2 channels are very effective at dampening the neuronal excitability, but less so at producing adaptation of action potential firing frequency. In addition, we suggest experimental ways to recognize HELK2 currents in vivo and raise the issue of the possible function of these channels in astrocytoma.
Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord
Authors: Bao Lan , Wang Hui Fredrik , Cai Hai‐Jiang , Tong Yong‐Guang , Jin Shan‐Xue , Lu Ying‐Jin , Grant Gunnar , Hökfelt Tomas , Zhang Xu 
Published: March 2003

AbstractPeripheral axotomy‐induced sprouting of thick myelinated afferents (A‐fibers) from laminae III–IV into laminae I–II of the spinal cord is a well‐established hypothesis for the structural basis of neuropathic pain. However, we show here that the cholera toxin B subunit (CTB), a neuronal tracer used to demonstrate the sprouting of A‐fibers in several earlier studies, also labels unmyelinated afferents (C‐fibers) in lamina II and thin myelinated afferents in lamina I, when applied after peripheral nerve transection. The lamina II afferents also contained vasoactive intestinal polypeptide and galanin, two neuropeptides mainly expressed in small dorsal root ganglion (DRG) neurons and C‐fibers. In an attempt to label large DRG neurons and A‐fibers selectively, CTB was applied four days before axotomy (pre‐injury‐labelling), and sprouting was monitored after axotomy. We found that only a small number of A‐fibers sprouted into inner lamina II, a region normally innervated by C‐fibers, but not into outer lamina II or lamina I. Such sprouts made synaptic contact with dendrites in inner lamina II. Neuropeptide Y (NPY) was found in these sprouts in inner lamina II, an area very rich in Y1 receptor‐positive processes. These results suggest that axotomy‐induced sprouting from deeper to superficial layers is much less pronounced than previously assumed, in fact it is only marginal. This limited reorganization involves large NPY immunoreactive DRG neurons sprouting into the Y1 receptor‐rich inner lamina II. Even if quantitatively small, it cannot be excluded that this represents a functional circuitry involved in neuropathic pain.
Lactate in the brain of the freely moving rat: voltammetric monitoring of the changes related to the sleep–wake states
Authors: Shram Nataliya , Netchiporouk Larissa , Cespuglio Raymond 
Published: March 2003

AbstractCortical lactate was monitored voltammetrically in freely moving rats equipped with polygraphic electrodes. Differential normal pulse voltammetric measurements were carried out using a lactate biosensor coated with lactate oxidase and cellulose acetate. Changes occurring in lactate level were in keeping with sleep–wake states. During slow wave sleep (SWS), the lactate level decreased significantly (−16.2%) vs. the spontaneous waking state (W) referenced to as 100%. During paradoxical sleep (PS), and still vs. W, it remained low (−9.0%) but this variation was not statistically significant. However, when this PS change was compared to the SWS variation, a significant increase in lactate level was then revealed (+8.5%). Finally, during the active waking (aW) triggered by a water puff stress, lactate level rose significantly in accordance with the animal activity (+53% compared to W). Long‐term monitoring also allowed the determination of a circadian component in lactate production, the lowest and highest values being monitored during light and dark periods, respectively. The acrophasis of the circadian change occurred during the dark period, about 3 h after the light‐off (+89%). It is suggested that during wakefulness astrocyte metabolism allows the transformation of the blood‐borne glucose into lactate. The increase in this substrate observed during PS may fulfil the oxidative phosphorylation in order to supply the important ATP need of PS.
New genomic avenues in behavioural neuroendocrinology *
Authors: Lightman S. L. , Insel T. R. , Ingram C. D. 
Published: March 2003

AbstractNeuroendocrine systems play a key role not only in the maintenance of whole‐body homeostasis but also as the link between behavioural, endocrine and autonomic responses to environmental stimuli. It is becoming increasingly clear that neuroendocrine regulatory mechanisms are under the control of a combination of factors including genetic background, environment and early‐life programming. Patterns of gene expression are increasingly being used to provide information on the genotypes associated with particular behaviours, and modulation of specific parts of the genome allow investigation of the contribution of particular genes. The sequencing of the genome provides a unique opportunity to elucidate the genetic contribution to neuroendocrine and behavioural processes, and to investigate the interactions between genetic and environmental factors. Although drugs can be used to activate or inhibit neurotransmitters and receptors, they lack specificity. New technologies now permit the activation or inactivation of both neurotransmitters and receptors in specific areas of the brain for defined periods, including crucially important developmental windows when activation appears to have long‐term consequences. The future challenges are to define the critical mechanisms through which the genetic constitution of an individual human or experimental animal interacts with environmental cues to result in altered physiological or even pathological behaviour and endocrine function.
Variation in the vasopressin V1a receptor promoter and expression: implications for inter‐ and intraspecific variation in social behaviour*
Authors: Hammock Elizabeth A. D. , Young Larry J. 
Published: March 2003

AbstractInstability in highly repetitive microsatellite DNA located in the regulatory regions of genes may be a major factor producing diversity in both region‐specific gene expression and the resulting phenotypes. Polymorphisms in promoter regions affecting expression of genes involved in regulating behaviour may play a role in generating individual variation in behaviour, including psychopathologies in humans, and probably are also important for the evolution of behaviour. Here we discuss the prairie vole vasopressin V1a receptor gene as a model that may be useful for understanding the evolution of promoter sequences and the relationship between gene sequence, expression and behavioural phenotype.
The neurosteroid allopregnanolone increases dopamine release and dopaminergic response to morphine in the rat nucleus accumbens
Authors: Rougé‐Pont Françoise , Mayo Willy , Marinelli Michela , Gingras Mireille , Le Moal Michel , Piazza Pier Vincenzo 
Published: March 2003

AbstractNeurosteroids are a subclass of steroids that can be synthesized in the central nervous system independently from peripheral sources. Clinical studies in humans have associated these hormones with depression and postpartum mood disorders. In rodents, allopregnanolone (AlloP) has been shown to have anxiolytic and rewarding properties. These observations suggest that neurosteroids could interact with mood and motivation. However, the possible neural substrates of these effects remain unknown. In this report, we have studied the action of AlloP on the activity of the mesencephalic dopaminergic (DA) projection to the nucleus accumbens, which is considered one of the biological substrates of motivation and reward. This study was conducted by measuring extracellular concentrations of dopamine (DA) in the nucleus accumbens by means of microdialysis in freely moving rats. We studied both the direct effect of AlloP and the influence of this hormone on the DA response to an injection of morphine. AlloP dose‐dependently increased the release of DA in the nucleus accumbens. Furthermore, this hormone doubled the DA response to morphine. These effects were observed for AlloP doses of 50 and 100 pmol injected intracerebroventricularly. These results suggest that the stimulatory effect of AlloP on DA could mediate some of the behavioural effects of neurosteroids and, in particular, the interaction of these hormones with mood and motivation.
Two mechanisms of protracted reaction times mediated by dissociable cortical networks
Authors: Herath Priyantha , Young Jeremy , Roland Per 
Published: March 2003

AbstractWhen people divide attention between two sensory modalities and respond rapidly to stimuli in either modality, the reaction times (RTs) are longer than when they selectively attend and respond to one sensory modality. There is a further increase in RT when subjects use different fingers to respond to stimuli from different modalities as compared to when they use the same finger for both modalities. Here we use functional magnetic resonance imaging to show that division of attention bilaterally activates the caudal prefrontal areas near the precentral sulcus and areas in the intraparietal sulcus. All RT tasks, whether different fingers for different modalities or one finger for both modalities was used, activated identical motor areas 4a, 4p, supplementary and cingulate, the basal ganglia and the ventral anterior thalami. The increased blood oxygen level‐dependent signal from motor cortical areas was anatomically distinct from the prefrontal/parietal areas. These anatomically dissociable neural substrates of division of attention and motor control may be responsible for the different types of RT delays that we have found. In the brain, there were no differences in the BOLD signal irrespective of whether the effector was specified a priori or was specified only after the sensory signal was received.
Long‐lasting modification of intrinsic discharge properties in subicular neurons following status epilepticus
Authors: Wellmer Jörg , Su Hailing , Beck Heinz , Yaari Yoel 
Published: March 2003

AbstractA single episode of status epilepticus (SE) induces neuropathological changes in the brain that may lead to the development of a permanent epileptic condition. Most studies of this plasticity have focused on the hippocampus, where both synaptic function and intrinsic neuronal excitability have been shown to be persistently modified by SE. However, many other brain structures are activated during SE and may also be involved in the subsequent epileptogenic process. Here we have investigated whether SE, induced in rats with pilocarpine and terminated after 40 min with diazepam, persistently modifies the intrinsic excitability of pyramidal neurons in the subiculum. Subicular slices were prepared from control and SE‐experienced rats (2–5 weeks after SE). In the control group, only 4% of the neurons fired bursts in response to intrasomatic, threshold‐straddling depolarizing current pulses (low‐threshold bursters). The remaining neurons either fired bursts in response to strong (3× threshold) depolarizations (35%; high‐threshold bursters) or fired in a completely regular mode (61%; nonbursters). In the SE‐experienced group, the fractions of low‐ and high‐threshold bursters markedly increased to 29% and 53%, respectively. This change in firing behaviour was associated with a marked increase in the size of the spike afterdepolarization, particularly in low‐threshold bursters. Experimental suppression of Ca2+currents selectively blocked low‐threshold bursting but did not affect high‐threshold bursting, suggesting that a dual Ca2+‐ dependent and Ca2+‐ independent mechanism controls bursting in these neurons. The persistent up‐regulation of intrinsic bursting in the subiculum, in concert with similar changes in the hippocampus, undoubtedly contributes to epileptogenesis following pilocarpine‐induced SE.
THIS ARTICLE HAS BEEN RETRACTED  Repeated massage‐like stimulation induces long‐term effects on nociception: contribution of oxytocinergic mechanisms
Authors: Lund Iréne , Yu Long‐Chuan , Uvnas‐Moberg Kerstin , Wang Jing , Yu Cheng , Kurosawa Mieko , Agren Greta , Rosén Annika , Lekman Magnus , Lundeberg Thomas 
Published: March 2003

AbstractMassage‐like stroking induces acute antinociceptive effects that can be reversed by an oxytocin antagonist, indicating activation of oxytocin on endogenous pain controlling systems. We now demonstrate an increase in hindpaw withdrawal latencies (HWLs), in response to thermal and mechanical stimuli, which was present after six treatments of massage‐like stroking every other day and which continued to increase through the remaining seven treatments. Repeated massage‐like stroking also resulted in increased oxytocin‐like immunoreactivity (oxytocin‐LI) levels in plasma and periaquaductal grey matter (PAG). Furthermore, increases in HWLs were also present after injections of oxytocin into the PAG (0.1, 0.5 and 1.0 nmol). Intra‐PAG oxytocin injection of 1 nmol followed by 1 or 20 nmol of naloxone attenuated the increments in HWL. Also, there was a dose‐dependent attenuation of the oxytocin‐induced antinociceptive effects following intra‐PAG injection of the µ‐opioid antagonist β‐funaltrexamine (β‐FNA) and the κ‐opioid antagonist nor‐binaltorphimine (nor‐BNI) but not the δ‐antagonist naltrindole. The long‐term antinociceptive effects of massage‐like stroking may be attributed, at least partly, to the oxytocinergic system and its interaction with the opioid system, especially the µ‐ and the κ‐receptors in the PAG.
Locomotor recovery in the chronic spinal rat: effects of long‐term treatment with a 5‐HT2 agonist
Authors: Antri M. , Orsal D. , Barthe J.‐Y. 
Published: March 2003

AbstractA complete transection of the spinal cord at a low thoracic level induces a paraplegic syndrome that is accompanied by a loss of spinal cord serotonin content. Former experimental data suggest that the central pattern generator for locomotion, located in the lumbar segments of the spinal cord, might be able to generate rhythmic motor outputs (similar to automatic walking under certain circumstances) involving exteroceptive stimulations and activation of serotonergic receptors. In the present study, we investigated the effects of a chronic treatment using a serotonergic agonist, delivered continuously to the sublesionned spinal cord, and its effect on motor function recovery. The data obtained from behavioural, kinematic and electromyographic measurements suggest that the chronic stimulation of 5‐HT2 type receptors allows motor function recovery. Behavioural measurements show a clear improvement in motor performances when compared to spinal animals (confirmed by kinematic observations): alternating steps and foot placement is recovered in these animals. However, electromyographic data demonstrate that the pattern of activation of the muscles is only restored partially.