bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential expression of alternative splice variants of β‐arrestin‐1 and ‐2 in rat central nervous system and peripheral tissues
Authors: Komori Naoka , Cain Sandra D. , Roch Jean‐Marc , Miller Kenneth E. , Matsumoto Hiroyuki 
Published: March 2003

AbstractMembers of arrestin/β‐arrestin protein family are thought to participate in agonist‐mediated desensitization of G‐protein‐coupled receptors, including rhodopsin and β2‐adrenergic receptor. Unlike in human and cow, splice variants of this protein family in rat have not been studied extensively, and there has been no report on their existence at protein level. Hence, a previous report by others on the localization of both β‐arrestin‐1 and ‐2 in a wide range of innervated rat tissues could imply their broad receptor specificity. In this report we show the presence of two alternatively spliced forms of β‐arrestin‐1 in several rat tissues using both reverse transcription–polymerase chain reaction and Western immunoblot. Splicing of β‐arrestin‐1 pre‐mRNA appears to be subject to differential regulation between the rat CNS and peripheral tissues. In contrast, we detected no splice variants of β‐arrestin‐2 in rat. A comparison of the genomic DNA sequences of bovine and rat β‐arrestin‐2, where the splicing of bovine β‐arrestin‐2 mRNA has been reported, revealed a high degree of homology in their organization of exons and introns as well as certain differences that might be responsible for the different processing of β‐arrestin‐2 mRNA in the two species. Our two‐dimensional isoelectric focusing gels using rat spinal cord and heart tissues demonstrate isoelectric heterogeneity of rat β‐arrestin‐1, suggesting that β‐arrestin‐1 is subject to post‐translational modification unlike β‐arrestin‐2.
An animal model of autism: behavioural studies in the GS guinea‐pig
Authors: Caston J. , Yon E. , Mellier D. , Godfrey H. P. , Delhaye‐Bouchaud N. , Mariani J. 
Published: March 2003

AbstractAutism is a human behavioural pathology marked by major difficulties in abnormal socialization, language comprehension and stereotypic motor patterns. These behavioural abnormalities have been associated with corticocerebral and cerebellar abnormalities in autistic patients, particularly in vermal folia VI and VII. Progress in understanding this disease has been hindered by the absence of a non‐primate animal model. GS guinea‐pigs are a partially inbred, non‐ataxic guinea‐pig strain with cerebellar and corticocerebral abnormalities similar to those reported to exist in human patients with autism. In order to determine if GS guinea‐pigs represent an animal model of autism, their behaviour was compared with that of Hartley strain guinea‐pigs. GS animals learned a motor task significantly more rapidly than Hartley guinea‐pigs, but performed it in a more stereotypic manner and were less influenced by environmental stimuli than Hartleys. GS animals exhibited significantly less exploratory behaviour in a novel environment and were significantly less responsive to 50–95 dBA pure tones than Hartley guinea‐pigs. In a social interaction assay, GS guinea‐pigs interacted significantly less frequently with each other or with Hartley guinea‐pigs than Hartleys did under the same conditions. GS behaviour thus exhibits autistic‐like behaviour patterns: motor stereotypy, lack of exploration and response to environment and poor social interaction. Coupled with the neuropathological findings, this abnormal behaviour suggests that GS guinea‐pigs could be a useful animal model of autism.
The expression of the glial glutamate transporter protein EAAT2 in motor neuron disease: an immunohistochemical study
Authors: Fray Anne E. , Ince Paul G. , Banner Steven J. , Milton Ian D. , Usher Philip A. , Cookson Mark R. , Shaw Pamela J. 
Published: March 2003

AbstractEmerging evidence suggests that a disturbance of the glutamate neurotransmitter system may be a contributory factor to motor neuron injury in motor neuron disease. Previous autoradiographic and immunoblotting studies have suggested that there may be reduced expression of glutamate transporter proteins in pathologically affected areas of the CNS in motor neuron disease. This study further explores the possible alteration in expression of the excitatory amino acid transporter protein EAAT2 in MND, by examining the protein expression in situ, in frozen sections, using immunohistochemistry. The aim of the study was to compare the distribution and density of EAAT2 in the motor cortex and spinal cord of MND cases (n = 16) compared with neurologically normal controls (n = 12), matched for relevant parameters. A novel, previously characterized, monoclonal antibody to EAAT2 was employed. EAAT2 immunoreactivity in motor neuron disease and control cases was compared using relative optical density measurements generated by computerized image analysis. In the motor cortex, EAAT2 immunoreactivity was laminated comprising a superficial intense band (corresponding to layers 1 and 2); a paler middle band (layer 3 and part of 5) and a more intense deep layer (layers 5 and 6). In the spinal cord, the ventral horn showed strong immunoreactivity with dense perisomatic staining around motor neuron cell bodies, the substantia gelatinosa showed moderate diffuse staining and the intermediate spinal laminae showed weak staining. This general pattern of immunoreactivity was preserved in the motor neuron disease cases. However, in the motor neuron disease cases compared with controls, the optical density values for EAAT2 immunoreactivity were significantly reduced in all grey matter regions of the lumbar spinal cord (P < 0.001) and were increased in the middle laminae of the motor cortex (P < 0.05). This study indicates that glutamate transporter pathology in motor neuron disease may be a more complex phenomenon than previously recognized.
The layout of orientation and ocular dominance domains in area 17 of strabismic cats
Authors: Löwel Siegrid , Schmidt Kerstin E. , Kim Dae‐Shik , Wolf Fred , Hoffsümmer Frank , Singer Wolf , Bonhoeffer Tobias 
Published: March 2003

AbstractIn the primary visual cortex of strabismic cats, the elimination of correlated activity between the two eyes enhances the segregation of the geniculocortical afferents into alternating ocular dominance domains. In addition, both tangential intracortical fibres and neuronal synchronization are severely reduced between neurons activated by different eyes. Consequently, ocular dominance columns belonging to different eyes are functionally rather independent. We wondered whether this would also affect the organization of orientation preference maps. To this end, we visualized the functional architecture of area 17 of strabismic cats with both optical imaging based on intrinsic signals and double labelling of orientation and ocular dominance columns with [14C]2‐deoxyglucose and [3H]proline. As expected, monocular iso‐orientation domains had a patchy appearance and differed for the two eyes, leading to a clear segregation of the ocular dominance domains. Comparison of ‘angle maps’ revealed that orientation domains exhibit a pinwheel organization as in normally reared cats. Interestingly, the map of orientation preferences did not show any breaks at the borders between ocular dominance columns: iso‐orientation domains were continuous across these borders. In addition, iso‐orientation contours tended to cross the borders of adjacent ocular dominance columns at right angles. These data suggest that the basic relations between the layout of orientation maps and ocular dominance columns are not disturbed by artificial decorrelation of binocular input. Therefore in cat area 17, the orientation map does not seem to be modified by experience‐dependent changes of thalamic input connections. This suggests the possibility that use‐dependent rearrangement of geniculocortical afferents into ocular dominance columns is due to Hebbian modifications whereby postsynaptic responsivity is constrained by the scaffold of the orientation map.
GABA‐dependent generation of ectopic action potentials in the rat hippocampus
Authors: Avoli Massimo , Methot Mario , Kawasaki Hiroto 
Published: March 2003

AbstractIntracellular recordings from CA3 pyramidal cells of rat hippocampus in a slice preparation revealed the occurrence of interictal epileptiform discharges and synchronous GABA‐mediated potentials during application of 4‐aminopyridine (4AP, 50 μm). The synchronous GABA‐mediated potential consisted of a sequence of early hyperpolarization, long‐lasting depolarization (LLD), and late hyperpolarization. Action potentials of variable amplitude occurred at the peak of the early hyperpolarization and during the LLD rising phase (48 of 64 cells); they were not prevented by membrane hyperpolarization and displayed inflections that were reminiscent of the initial segment‐somatodendritic (IS‐SD) fractionation. Interictal discharges were blocked by excitatory amino acid receptor antagonists, while both GABA‐mediated potentials and action potentials of variable amplitude continued to occur (n = 10). The latter events were still recorded in the presence of the GABAB receptor antagonist CGP‐35348 (0.5–1 mm, n = 4), but were abolished by the GABAA receptor antagonist bicuculline methiodide (BMI, 10 μm, n = 5). Localized application of BMI (20 μm, n = 6) or tetrodotoxin (TTX, 5 μm, n = 3) to the CA1 stratum radiatum blocked the variable amplitude action potentials; these effects were not seen when BMI (n = 4) or TTX (n = 4) were applied to the CA3 stratum radiatum, although both procedures made LLDs disappear. Our findings indicate that action potentials of variable amplitude recorded from CA3 pyramidal cells in the 4AP model are generated at or near the terminal region of the Schaffer collaterals and that they represent TTX‐sensitive ectopic events. These action potentials are generated at this site by a BMI‐sensitive (and thus GABAA‐mediated) mechanism. We propose that the ectopic action potentials reflect an increased excitability of axon terminals that is presumably caused by [K+]o elevations associated with the 4AP‐induced synchronous GABA‐mediated potential.
Spatial‐frequency tuning and geniculocortical projections in the visual cortex (areas 17 and 18) of the pigmented ferret
Authors: Baker Gary E. , Thompson I. D. , Krug K. , Smyth D. , Tolhurst D. J. 
Published: March 2003

AbstractWe have examined the spatial‐frequency selectivity of neurons in areas 17 and 18 of the adult pigmented ferret, by measuring how the amplitude of response depends on the spatial‐frequency of moving sinusoidal gratings of optimal orientation and fixed contrast. Neurons in area 17 of the ferret respond optimally to low spatial frequencies [average 0.25 cycles per degree (c/deg)], much lower than the optima for cat area 17. The tuning curves are of the same form as those found in cat and monkey: unimodal with bandwidths in the range 0.8–3.5 octaves. Neurons in area 18 of the ferret respond optimally to even lower spatial frequencies (average 0.087 c/deg) than area 17 neurons, and the distributions of optimal spatial frequency for areas 17 and 18 hardly overlap. In both cortical areas, the bandwidth of the tuning curves is inversely correlated with optimal spatial frequency. This marked difference in tuning between the two cortical areas is probably attributable to differential geniculo‐cortical projections. Small injections of fluorescent latex microspheres or horseradish peroxidase (HRP) were made into area 17 or area 18 in order to investigate the populations of geniculate neurons projecting to the two cortical areas. After injections into area 17, labelled neurons are found predominantly in the geniculate A layers, with a few neurons labelled in the C layers. Conversely, after an area 18 injection, similar numbers of labelled neurons are found in the C layers as in the A layers. Soma‐size analysis of the neurons in the A‐layers suggests the existence of two populations of relay neurons, which project differentially to areas 17 and 18. The different geniculate inputs and the different spatial‐frequency tuning in areas 17 and 18 may imply that the two cortical areas process visual information more in parallel than in series.
The cytokine network of Wallerian degeneration: IL‐10 and GM‐CSF
Authors: Be′eri Hadassah , Reichert Fanny , Saada Ann , Rotshenker Shlomo 
Published: March 2003

AbstractWallerian degeneration (WD) is the inflammatory response of peripheral nerves to injury. Evidence is provided that granulocyte macrophage colony stimulating factor (GM‐CSF) contributes to the initiation and progression of WD by activating macrophages and Schwann, whereas IL‐10 down‐regulates WD by inhibiting GM‐CSF production. A significant role of activated macrophages and Schwann for future regeneration is myelin removal by phagocytosis and degradation. We studied the timing and magnitude of GM‐CSF and IL‐10 production, macrophage and Schwann activation, and myelin degradation in C57BL/6NHSD and C57BL/6‐WLD/OLA/NHSD mice that display normal rapid‐WD and abnormal slow‐WD, respectively. We observed the following events in rapid‐WD. The onset of GM‐CSF production is within 5 h after injury. Production is steadily augmented during the first 3 days, but is attenuated thereafter. The onset of production of the macrophage and Schwann activation marker Galectin‐3/MAC‐2 succeeds that of GM‐CSF. Galectin‐3/MAC‐2 production is up‐regulated during the first 6 days, but is down‐regulated thereafter. The onset of myelin degradation succeeds that of Galectin‐3/MAC‐2, and is almost complete within 1 week. IL‐10 production displays two phases. An immediate low followed by a high that begins on the fourth day, reaching highest levels on the seventh. The timing and magnitude of GM‐CSF production thus enable the rapid activation of macrophages and Schwann that consequently phagocytose and degrade myelin. The timing and magnitude of IL‐10 production suggest a role in down‐regulating WD after myelin is removed. In contrast, slow‐WD nerves produce low inefficient levels of GM‐CSF and IL‐10 throughout. Therefore, deficient IL‐10 levels cannot account for inefficient GM‐CSF production, whereas deficient GM‐CSF levels may account, in part, for slow‐WD.
Induction of long‐term potentiation at spinal synapses by noxious stimulation or nerve injury
Authors: Sandkühler Jürgen , Liu Xianguo 
Published: March 2003

AbstractUse‐dependent long‐term potentiation of synaptic strength (LTP) is an intensively studied model for learning and memory in vertebrates. Induction of LTP critically depends on the stimulation parameters of presynaptic fibres with synchronous high‐frequency bursts being most effective at many central synapses. It is, however, not known whether naturally occurring discharge patterns may induce LTP and whether LTP has any biological function in sensory systems. Here we have investigated the LTP of excitatory synaptic transmission between primary afferent C‐fibres, many of which are nociceptors, and neurons in rat superficial spinal dorsal horn. LTP that lasted for 4–6 h could not only be induced by electrical stimulation of sural nerve but also by natural stimulation of heat‐, mechano‐ or chemosensitive nociceptors in the skin or by acute nerve injury. Maintenance of LTP was not affected when afferent nerves were cut 1 h or 5 min after noxious skin stimulation, indicating that an ongoing afferent barrage is not required. Natural noxious stimuli induced LTP in animals which were spinalized but were ineffective in intact animals. Thus, induction of LTP is suppressed by tonically active supraspinal descending systems. We conclude that the natural non‐synchronized discharge patterns that are evoked by noxious stimulation may induce LTP and that this new form of LTP may be an underlying mechanism of afferent induced hyperalgesia.
Quinolinic acid‐induced inflammation in the striatum does not impair the survival of neural allografts in the rat
Authors: Duan Wei‐Ming , Widner Håkan , Cameron Reynolds M. , Brundin Patrik 
Published: March 2003

AbstractIt has been suggested that inflammation related to intracerebral transplantation surgery can affect the survival of intrastriatal neural allografts. To test this hypothesis, we transplanted dissociated embryonic mesencephalic tissue from one of two rat strains, Lewis (allogeneic grafts) or Sprague–Dawley (syngeneic grafts), to the striatum of Sprague–Dawley rats. The target striatum was either intact or had received a local injection of quinolinic acid 9 days earlier, in order to induce a marked inflammation. At 6 or 12 weeks after transplantation, there was no significant difference between the different groups regarding the number of surviving grafted tyrosine hydroxylase immunoreactive neurons. However, the graft volume of both the syngeneic and allogeneic implants was significantly larger in the quinolinate‐lesioned than in the intact striatum. There were dramatically increased levels of expression of major histocompatibility complex class I and II antigens, marked infiltrates of macrophages, activated microglia and astrocytes, and accumulation of large numbers of CD4 and CD8 positive T‐lymphocytes in the quinolinate‐lesioned striatum. In contrast, these immunological markers were much less abundant around both syngeneic and allogeneic grafts placed in intact striatum. We conclude that severe inflammation caused by quinolinic acid does not lead to rejection of intrastriatal neural allografts.
5HT1A‐receptors and behaviour under chronic stress: selective counteraction by testosterone
Authors: Flügge G. , Kramer M. , Rensing S. , Fuchs E. 
Published: March 2003

AbstractBehaviour of chronically stressed male tree shrews is characterized by a reduction in scent marking, self‐grooming and overall locomotor activity. It has been proposed that this subordination behaviour is related to the down‐regulation of 5HT1A‐receptors occurring in distinct brain regions of the animals. The high cortisol concentrations which accompany chronic stress are supposed to induce 5HT1A‐receptor down‐regulation. Because chronic stress in males also decreases androgen levels we investigated whether behaviour and 5HT1A‐receptor expression could be renormalized by testosterone replacement. Male tree shrews were submitted to subordination stress for 28 days, while during the last 18 days, onegroup was treated with testosterone and one with vehicle. Scent marking, self‐grooming, and overall locomotor activity were monitored, and cortisol levels were measured in morning urine during the whole experiment. Brain 5HT1A‐receptors were quantified by in vitro receptor autoradiography. Although in subordinate animals cortisol levels remained high during the testosterone treatment, 5HT1A‐receptors in the hippocampal formation and the occipital cortex were renormalized to control levels by the androgen, but 5HT1A‐receptors in the ventromedial thalamic nucleus did not return to base line levels. Scent marking and self‐grooming behaviour were both renormalized by testosterone, but overall locomotor activity did not return to base line levels. These data indicate that a balance between glucocorticoids and androgens is necessary to maintain ‘normal’ numbers of the monoamine receptors. The fact that both, 5HT1A‐receptors and certain behaviours can be renormalized by the sex steroid supports the view that 5HT1A‐receptor are involved in the regulation of stress behaviour. However, the fact that overall locomotor activity was not returned to baseline indicates that different types of behaviour are distinctly regulated.
Differential acetylcholine and GABA release from cultured chick retina cells
Authors: Santos Paulo F. , Carvalho Ana L. , Carvalho Arsélio P. , Duarte Carlos B. 
Published: March 2003

AbstractIn the present work we investigated the mechanisms controlling the release of acetylcholine (ACh) and of γ‐aminobutyric acid (GABA) from cultures of amacrine‐like neurons, containing a subpopulation of cells which are simultaneously GABAergic and cholinergic. We found that 81.2 ± 2.8% of the cells present in the culture were stained immunocytochemically with an antibody against choline acetyltransferase, and 38.5 ± 4.8% of the cells were stained with an antibody against GABA. Most of the cells containing GABA (87.0 ± 2.9%) were cholinergic. The release of acetylcholine and GABA was mostly Ca2+‐dependent, although a significant release of [3H]GABA occurred by reversal of its transporter. Potassium evoked the Ca2+‐dependent release of [3H]GABA and [3H]acetylcholine, with EC50 of 31.0 ± 1.0 mm and 21.6 ± 1.1 mm, respectively. The Ca2+‐dependent release of [3H]acetylcholine was significantly inhibited by 1 μm tetrodotoxin and by low (30 nm) ω‐conotoxin GVIA (ω‐CgTx GVIA) concentrations, or by high (300 nm) nitrendipine (Nit) concentrations. On the contrary, the release of [14C]GABA was reduced by 30 nm nitrendipine, or by 500 nmω‐CgTx GVIA, but not by this toxin at 30 nm. The release of either transmitters was unaffected by 200 nmω‐Agatoxin IVA (ω‐Aga IVA), a toxin that blocks P/Q‐type voltage‐sensitive Ca2+ channels (VSCC). The results show that Ca2+‐influx through ω‐CgTx GVIA‐sensitive N‐type VSCC and through Nit‐sensitive L‐type VSCC induce the release of ACh and GABA. However, the significant differences observed regarding the Ca2+ channels involved in the release of each neurotransmitter suggest that in amacrine‐like neurons containing simultaneously GABA and acetylcholine the two neurotransmitters may be released in distinct regions of the cells, endowed with different populations of VSCC.
Axonal injury and peripheral nerve grafting in the thalamus and cerebellum of the adult rat: upregulation of c‐jun andcorrelation with regenerative potential
Authors: Vaudano E. , Campbell G. , Hunt S. P. , Lieberman A. R. 
Published: March 2003

AbstractThe protooncogene c‐junis highly expressed for long periods in axotomized PNS neurons. This may be related to their growth and regeneration. In contrast, axotomized CNS neurons show only a small and transient upregulation of c‐jun. It has been suggested that there may be a correlation between this failure to maintain high levels of c‐junexpression after axotomy and abortive CNS axonal regeneration. We have studied, byin situhybridization and immunohistochemistry, the c‐junresponse after stab wound lesion, and after peripheral nerve grafting in the thalamus and cerebellum of the adult rat. A lesion elicits upregulation of c‐junin thalamic neurons ipsilateral to the lesion. This is most evident and prolonged in neurons such as those of the thalamic reticular nucleus, which have an established propensity to regenerate. After peripheral nerve grafting, the c‐junresponse in thalamic neurons is enhanced, mostly in neurons which have axons regenerating along the grafts. These neurons also upregulate growth‐associated protein 43 (GAP‐43). By comparison, injured Purkinje cells of the cerebellum which do not regenerate their axons along a graft, do not upregulate either c‐junorGAP‐43, although they increase their expression of p75. Thus CNS neurons able to regenerate their axons along a peripheral nerve graft are those in which c‐junis induced after injury, and c‐junmay play a critical role in the control of gene programs for axonal regeneration. Moreover, the observed differences in the ability of CNS neurons to regenerate their axons may relate to a difference in their intrinsic molecular response to axotomy.