bluuebunny/crossref_metadata_2025_split huggingface dataset:
GDNF reverses priming for dyskinesia in MPTP‐treated, l‐DOPA‐primed common marmosets
Authors: Iravani Mahmoud M. , Costa Sergio , Jackson Michael J. , Tel Banu C. , Cannizzaro Carla , Pearce Ronald K. B. , Jenner Peter 
Published: March 2003

AbstractParkinson's disease (PD) is associated with a progressive loss of dopamine neurons in the substantia nigra and degeneration of dopaminergic terminals in the striatum. Although l‐DOPA treatment provides the most effective symptomatic relief for PD it does not prevent the progression of the disease, and its long‐term use is associated with the onset of dyskinesia. In rodent and primate studies, glial cell line‐derived neurotrophic factor (GDNF) may prevent 6‐OHDA‐ or MPTP‐induced nigral degeneration and so may be beneficial in the treatment of PD. In this study, we investigate the effects of GDNF on the expression of dyskinesia in l‐DOPA‐primed MPTP‐treated common marmosets, exhibiting dyskinesia. GDNF or saline was administered by two intraventricular injections, 4 weeks apart, to MPTP‐treated, l‐DOPA‐treated common marmosets primed to exhibit dyskinesia. Prior to GDNF or saline administration, all animals displayed marked dyskinesia when treated with l‐DOPA. GDNF administration produced a significant improvement in motor disability and, following the second injection of GDNF, a significant improvement in the locomotor activity was observed. Following the administration of l‐DOPA there was a greater reversal of disability and a reduction in the intensity of l‐DOPA‐induced dyskinesia in GDNF‐treated animals compared to saline‐treated controls. However, there was no significant difference in l‐DOPA's ability to increase locomotor activity between GDNF‐treated and saline‐treated animals. GDNF treatment caused a significant increase in the number of tyrosine hydroxylase‐positive neurons in the substantia nigra, but no change in [3H]mazindol binding to dopamine terminals was found in the striatum of GDNF‐treated animals compared to saline‐treated controls. In GDNF‐treated animals a small but significant reduction in enkephalin mRNA was observed in the caudate nucleus but not in the putamen or the nucleus accumbens. Substance P mRNA expression was equally reduced in the caudate nucleus and the putamen of the GDNF‐treated animals but not in the nucleus accumbens. Intraventricular administration of GDNF improved MPTP‐induced disability and reversed dopamine cell loss in the substantia nigra. GDNF also diminished l‐DOPA‐induced dyskinesia, which may relate to its ability to partly restore nigral dopaminergic transmission or to modify the activity of striatal output pathways.
Cloning and functional expression of GABAB receptors from Drosophila
Authors: Mezler Mario , Müller Thomas , Raming Klaus 
Published: March 2003

AbstractThe neurotransmitter GABA (γ‐aminobutyric acid) functions as the major inhibitory neurotransmitter in the central nervous system of vertebrates and invertebrates. In vertebrates GABA signals both through ionotropic receptors (GABAA, GABAC), which induce fast synaptic inhibitory responses, and through metabotropic receptors (GABAB), which play a fundamental role in the reduction of presynaptic transmitter release and postsynaptic inhibitory potentials. Whilst GABAA and GABAC receptors have been cloned from vertebrates as well as invertebrates, GABAB receptors have only been identified in vertebrate species to date, although indirect evidence suggests their existence in arthropods, too. Here we report the cloning of three putative invertebrate GABAB receptor subtypes (D‐GABABR1, R2 and R3) isolated from Drosophila melanogaster. Whilst D‐GABABR1 and R2 show high sequence identity to mammalian GABABR1 and R2, respectively, the receptor D‐GABABR3 seems to be an insect‐specific subtype with no known mammalian counterpart so far. All three D‐GABABR subtypes are expressed in the embryonic central nervous system. In situ hybridization of Drosophila melanogaster embryos shows that two of the D‐GABABRs (D‐GABABR1 and R2) are expressed in similar regions, suggesting a coexpression of the two receptors, whilst the third D‐GABABR (D‐GABABR3) displays a unique expression pattern. In agreement with these results we have only been able to functionally characterize D‐GABABR1 and R2 when the two subtypes are coexpressed either in Xenopus laevis oocytes or mammalian cell lines, whilst D‐GABABR3 was inactive in any combination. The pharmacology of the coexpressed D‐GABABR1/2 receptor was different from the mammalian GABABRs: e.g. baclofen, an agonist of mammalian GABABRs, showed no effect.
Activation of murine microglial cell lines by lipopolysaccharide and interferon‐γ causes NO‐mediated decreases in mitochondrial and cellular function
Authors: Moss David W. , Bates Timothy E. 
Published: March 2003

AbstractActivation of murine microglial and macrophage cell lines with lipopolysaccharide (LPS) and interferon‐γ (IFN‐γ) resulted in the induction of the inducible form of nitric oxide synthase (NOS) and the release of micromolar amounts of NO into the surrounding medium. The synthesis of NO was associated with increased cellular membrane damage as assessed by trypan blue dye exclusion and the leakage of lactate dehydrogenase into the cell culture medium. However, the synthesis and release of cytokines was largely unaffected. NO‐mediated cell damage was also accompanied by a marked decrease in the intracellular levels of reduced glutathione and ATP. In addition, significant inhibition of mitochondrial respiratory chain enzyme activities was seen following cellular activation. However, citrate synthase activity (a mitochondrial matrix enzyme) was not detectable in the extracellular supernatants, suggesting preservation of the integrity of the mitochondrial inner membrane following activation. These effects were largely prevented by the addition of the NOS inhibitor, N‐guanidino monomethyl l‐arginine during the activation period. Our observations demonstrate that induction of NOS activity in microglia results in damage to the plasma membrane leading to a loss of glutathione, complex‐specific inhibition of the mitochondrial electron transport chain and depletion of cellular ATP. Our data suggest that pharmacological modulation of NOS activity in activated microglia in vivo may prevent cellular damage to bystander cells such as neurons, astrocytes and oligodendrocytes, as well as to microglia themselves.
Functional projection distances of spinal interneurons mediating reciprocal inhibition during swimming in Xenopus tadpoles
Authors: Soffe S. R. , Zhao F.‐Y. , Roberts Alan 
Published: March 2003

AbstractThe basis for longitudinal coordination among spinal neurons during locomotion is still poorly understood. We have now examined the functional projection distances for the longitudinal axons of reciprocal inhibitory ‘commissural interneurons’ in the spinal cord of young Xenopus tadpoles. In quiescent animals, glycinergic inhibitory postsynaptic potentials (IPSPs) were evoked in ventral spinal neurons by stimulating small rostral and caudal groups of commissural interneuron somata at different distances on the opposite side of the hindbrain and spinal cord. Unitary IPSPs, produced by single synaptic contacts, could be distinguished from background noise. Local cord stimulation at different distances revealed maximum functional projection distances up to ∼ 0.5 mm for both descending and ascending axons, but with the probability of recording connections falling steeply over this distance. These maximum longitudinal projection distances are smaller than predicted by axonal anatomy (∼ 1.2 mm). We then measured functional projection distances during swimming by examining the synaptic output of a surgically isolated group of rostral commissural interneurons, mapping the occurrence of the mid‐cycle, reciprocal IPSPs they produced in more caudal neurons. IPSPs occurred with high probability up to 0.9 mm away, nearly twice the projection distance found in quiescent tadpoles. These results show that synaptic contacts from commissural interneurons could influence longitudinal coupling during swimming at distances of up to 0.9 mm (∼ 4–5 myotome segments or ∼ 25% of the spinal cord). They provide direct evidence for functional projection distances of a characterized class of interneurons belonging to a spinal locomotor pattern generator.
The selective cyclooxygenase‐2 inhibitor rofecoxib reduces kainate‐induced cell death in the rat hippocampus
Authors: Kunz Tina , Oliw Ernst H. 
Published: March 2003

AbstractTreatment of male Sprague–Dawley rats with kainic acid (10 mg/kg, i.p.) triggered limbic seizures in 60% of the animals starting within 30 min and lasting for about 6 h. Cyclooxygenase‐2 (COX‐2) mRNA was strongly induced in the pyramidal cells of the hippocampus, in the amygdala and the piriform cortex after 8 h, as shown by in situ hybridization, and returned to control levels after 72 h. At this time marked cell loss occurred in the CA1–CA3 areas of the hippocampus. We hypothesize that rofecoxib, a selective COX‐2 inhibitor, might abbreviate the late neurotoxicity, possibly associated with COX‐2 induction. Animals which developed seizures were treated for 3 days with rofecoxib (10 mg/kg, i.p., n = 12) starting 6 or 8 h after kainic acid injection. Histological staining of viable cells confirmed that rofecoxib treatment selectively diminished cell loss in the hippocampus. The TdT‐mediated dUTP nick end labelling (TUNEL) technique was used to estimate delayed cell death. Abundant TUNEL‐positive cells were detected in seizure rats 72 h after kainic acid injection in pyramidal cells of the hippocampus (CA1–CA3), in cells of the thalamus, the amygdala and the piriform cortex. Treatment with rofecoxib selectively and significantly (P < 0.05) attenuated the number of TUNEL‐positive cells in the hippocampus, whereas the cells of the thalamus, amygdala and piriform cortex were not protected. Therefore we conclude that COX‐2 might contribute to cell death of pyramidal cells of the hippocampus as a consequence of limbic seizures.
Subunits of the nitric oxide receptor, soluble guanylyl cyclase, expressed in rat brain
Authors: Gibb Barry J. , Garthwaite John 
Published: March 2003

AbstractDespite the widespread use of nitric oxide as a signalling molecule in the central nervous system, the molecular makeup of its receptor, soluble guanylyl cyclase (sGC), therein is poorly understood. Accordingly, RT‐PCR and in situ hybridization were used to identify sGC subunits expressed in rat brain. In addition to the expected mRNA for α1 and β1 subunits, message for the β2 subunit was detected in the cerebellum at all developmental stages investigated (1–150 days postnatum). The use of degenerate primers allowed the identification of mRNA coding for the rat α2 subunit, which was also expressed at every age studied. All but β2 were detected by in situ hybridization in the brains of both 8‐day‐old and adult rats. The distribution patterns indicated that in some areas, e.g. caudate–putamen and nucleus accumbens, sGC probably exists mainly as the α1β1 heterodimer. In others, e.g. hippocampus and olfactory bulb, α2β1 is likely to be dominant. In the cerebellum, α1 and β1 message was strong in the Purkinje cell layer but was not confined to Purkinje cells: smaller cells, presumed to be the Bergmann glia, were also labelled. In contrast, α2 mRNA was concentrated in cerebellar granule cells. Western blotting indicated an excess of α1 over β1 protein in the cerebellum, the reverse of what was found in the lung. It is concluded that, in molecular terms, sGC is likely to be more complex and exhibit more regional variation in the brain than previously thought. The functional consequences of this heterogeneity require investigation.
Olfactory learning is associated with increased spine density along apical dendrites of pyramidal neurons in the rat piriform cortex
Authors: Knafo Shira , Grossman Yoram , Barkai Edi , Benshalom Gadi 
Published: March 2003

AbstractWe studied the effect of olfactory learning on the dendritic spine density of pyramidal neurons in the rat piriform (olfactory) cortex. Rats were trained to distinguish between two pairs of odours in an olfactory discrimination task. Three days after training completion, rats were killed and layer II pyramidal neurons identified by Golgi impregnation were examined with a light microscope. Counts of visible spines were performed along the secondary and tertiary branches of both the apical dendrites and the basal dendrites, which are the sites of intracortical synaptic inputs. An estimate of the true spine density was obtained using Feldman and Peters' method (1979, The Journal of Comparative Neurology, 188, 527–542). The estimated true spine density along apical dendrites was higher in neurons from trained rats than those in pseudotrained and naive rats by 15%. As length of spiny dendrites did not change significantly after learning, the learning‐related increase in spine density in neurons from trained rats may indicate on an increased number of excitatory synapses interconnecting pyramidal neurons in the piriform cortex, following olfactory learning.
Peripheral auditory asymmetry in infantile autism
Authors: Khalfa S. , Bruneau N. , Rogé B. , Georgieff N. , Veuillet E. , Adrien J.‐L. , Barthélémy C. , Collet L. 
Published: March 2003

AbstractDifficulty in filtering relevant auditory information in background noise is one of the features of autism. Auditory filtering processes can be investigated at the peripheral level as they are hypothesized to involve active cochlear mechanisms which are regulated by the efferent activity of the medial olivocochlear (MOC) system. The aim of the present work was therefore to assess these peripheral auditory processes in 22 children and adolescents with autism compared with age‐ and gender‐matched normal controls. Active cochlear mechanisms were evaluated with transiently evoked otoacoustic emissions (TEOAEs) and MOC system efficiency was assessed via TEOAEs which are decreased when stimulating the contralateral ear with noise. The MOC system evaluation was performed on 18 of the 22 children. In both studies, results were analysed according to age (from 4 to 10 years and from 11 to 20 years). The main result concerns the asymmetry of the efferent system which differs in individuals with autism. Several neural processes might be hypothesized as involved in the results obtained as the MOC system which originates in the brainstem received regulating controls from upper brain structures including auditory cortex. Lateralization abnormalities at the auditory periphery may reflect indirectly a problem at a higher level of auditory processing. A second important result shows a decrease in TEOAE amplitude with age, in patients, that may correspond to a decrease in hearing sensitivity.
Influence of injury and cytokines on synthesis of monocyte chemoattractant protein‐1 mRNA in peripheral nervous tissue
Authors: Subang M. C. , Richardson P. M. 
Published: March 2003

AbstractThe signals and the source of the signals for monocyte/macrophage entry into the injured peripheral nervous tissue are not yet defined. This study was undertaken to determine the distribution of the chemokine monocyte chemoattractant protein‐1 mRNA in injured rat and mouse nerves and to investigate the mechanisms that regulate its synthesis in rat Schwann cells. Results from RNase protection assays showed that, following sciatic nerve transection in rats, mRNA for monocyte chemoattractant protein‐1 was induced at the site of lesion within 3 h of surgery and in more distal segments from 24 h for at least 8 days. In cultured Schwann cells, tumour necrosis factor‐α but not interleukin‐1β, interleukin‐6, transforming growth factor‐β1, platelet‐derived growth factor‐BB or nerve growth factor induced monocyte chemoattractant protein‐1 mRNA in a time‐ and dose‐dependent fashion. The induction of monocyte chemoattractant protein‐1 mRNA in Schwann cells treated with tumour necrosis factor‐α was reduced by inhibitors of nuclear factor‐κB and the p38 mitogen‐activated protein kinase. In mice that lack the two receptors for tumour necrosis factor, the message for JE, a murine homologue of monocyte chemoattractant protein‐1, was still induced within 6 h of injury at the lesion site. However, in more distal segments 4 days after transection the concentration of JE mRNA was lower than that of control mice. Tumor necrosis factor‐α is the only cytokine that was shown to induce monocyte chemoattractant protein‐1 mRNA in cultured Schwann cells and is one of the factors that regulate the synthesis of monocyte chemoattractant protein‐1 in injured nerves.
Developmental and cellular expression pattern of epithelial sodium channel α, β and γ subunits in the inner ear of the rat
Authors: Gründer Stefan , Müller Andrea , Ruppersberg J. Peter 
Published: March 2003

AbstractEndolymphatic ion composition in the adult inner ear is characterized by high K+ and low Na+ concentration. This unique ion composition is essential for proper functioning of sensory processing. Although a lot has been learned in recent years about molecules involved in K+ transport in inner ear, the molecules involved in Na+ transport are only beginning to emerge. The epithelial Na+ channel (ENaC) is a highly selective Na+ channel that is expressed in many Na+‐reabsorbing tissues. The aim of our study was to investigate whether ENaC is expressed in inner ear of rats and could account for Na+ reabsorption from endolymph. We detected mRNA for the three channel‐forming subunits (α, β and γENaC) in cochlea, vestibular system and endolymphatic sac. mRNA abundance increased during the first 12 days of life in cochlea and vestibular system, coinciding with decreasing Na+ concentration in endolymph. Expression was strongest in epithelial cells lining scala media, most notably Claudius' cells. As these cells are characterized by a very negative resting potential they would be ideally suited for reabsorption of Na+. mRNA abundance in endolymphatic sac decreased during the first 6 days of life, suggesting that ENaC might be implicated in reabsorption of endolymph in the endolymphatic sac of neonatal animals. Together, our results suggest that the epithelial Na+ channel is a good candidate for a molecule involved in Na+ homeostasis in inner ear.
The highly sialylated isoform of the neural cell adhesion molecule is required for estradiol‐induced morphological synaptic plasticity in the adult arcuate nucleus
Authors: Hoyk ZS. , Parducz A. , Theodosis D. T. 
Published: March 2003

AbstractThe large quantities of polysialic acid (PSA) characterizing highly sialylated isoform of the neural cell adhesion molecule (PSA‐NCAM), greatly reduce cell adhesion and render this particular cell surface adhesion molecule a likely candidate to intervene in dynamic neuronal phenomena, such as synaptic plasticity. The hypothalamic arcuate nucleus expresses high levels of PSA‐NCAM and maintains a high capacity for neuroplastic changes in the adult. Thus, in the arcuate nucleus of female rats, varying circulating levels of estrogen give rise to a reversible reduction in the number of axo‐somatic GABA synapses, together with a changing ensheathing of neuronal somata by astrocytes. To examine the role of PSA in such changes, we perturbed its expression, either by blockade with antibodies raised against this carbohydrate moiety (delivered intracerebroventricularly), or by its enzymatic cleavage after microinjection of endoneuraminidase N over the arcuate nucleus. Either procedure was performed in ovariectomized adult rats that received concurrent treatment with 17β‐estradiol. Morphological synaptic plasticity was analysed using the unbiased disector method to assess synaptic densities in ultrathin sections of the arcuate nucleus immunogold‐labelled for GABA. As expected, 17β‐estradiol induced a significant reduction in the number of GABAergic axo‐somatic synapses, a reduction which did not occur after infusion of anti‐PSA antibodies or in vivo enzymatic removal of PSA from NCAM. Taken together, our results provide strong evidence that the presence of large quantities of the PSA moiety on NCAM is a necessary prerequisite for estrogen‐induced phasic remodelling of synapses in the adult female arcuate nucleus.
Progression of spontaneous seizures after status epilepticus is associated with mossy fibre sprouting and extensive bilateral loss of hilar parvalbumin and somatostatin‐immunoreactive neurons
Authors: Gorter J. A. , Van Vliet E. A. , Aronica E. , Da Silva F. H. Lopes 
Published: March 2003

AbstractThe development of spontaneous limbic seizures was investigated in a rat model in which electrical tetanic stimulation of the angular bundle was applied for up to 90 min. This stimulation produced behavioural and electrographic seizures that led to a status epilepticus (SE) in most rats (71%). Long‐term EEG monitoring showed that the majority of the rats (67%) that underwent SE, displayed a progressive increase of seizure activity once the first seizure was recorded after a latent period of about 1 week. The other SE rats (33%) did not show this progression of seizure activity. We investigated whether these different patterns of evolution of spontaneous seizures could be related to differences in cellular or structural changes in the hippocampus. This was the case regarding the following changes. (i) Cell loss in the hilar region: in progressive SE rats this was extensive and bilateral whereas in nonprogressive SE rats it was mainly unilateral. (ii) Parvalbumin and somatostatin‐immunoreactive neurons: in the hilar region these were almost completely eliminated in progressive SE rats but were still largely present unilaterally in nonprogressive SE rats. (iii) Mossy fibre sprouting: in progressive SE rats, extensive mossy fibre sprouting was prominent in the inner molecular layer. In nonprogressive SE rats, mossy fibre sprouting was also present but less prominent than in progressive SE rats. Although mossy fibre sprouting has been proposed to be a prerequisite for chronic seizure activity in experimental temporal lobe epilepsy, the extent of hilar cell death also appears to be an important factor that differentiates between whether or not seizure progression will occur.
Real‐time, two‐dimensional visualization of ischaemia‐induced glutamate release from hippocampal slices
Authors: Uchino Shigeo , Nakamura Takeshi , Nakamura Kyoko , Nakajima‐Iijima Sadayo , Mishina Masayoshi , Kohsaka Shinichi , Kudo Yoshihisa 
Published: March 2003

AbstractThe involvement of excitatory amino acid (EAA) toxicity in ischaemia‐induced neuronal cell death has long been suggested. However, in the hippocampus, the brain site most vulnerable to ischaemia, the detailed spatial and temporal patterns of EAA release are not yet known. To address this issue, we have developed a novel strategy for the continuous, real‐time, two‐dimensional monitoring of EAA release from brain slices. As EAA detector, we used a cell line transformed with the N‐methyl‐d‐aspartate (NMDA) receptor, which is exclusively activated by EAAs, leading to an increase in the intracellular Ca2+ level. Combined with a calcium imaging technique, the use of this cell line allowed the temporal and regional analysis of EAA release from a brain slice placed directly on top of the clonal cells in a culture dish. Using this strategy, we demonstrated ischaemia‐induced EAA release in rat hippocampal slices. Increased EAA release was seen initially in the CA1 region, about 3 min after the beginning of ischaemia, then in the CA3 region and dentate gyrus, and, finally, throughout the hippocampal slice. Regional differences in extracellular EAA levels were also seen, with more EAA being released from the CA1 region than from the middle dentate gyrus. The present results are especially interesting as neurons in the CA1 region are more vulnerable to ischaemia than those in the CA3 region and dentate gyrus.