bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased β‐Amyloid Precursor Protein Expression in Astrocytes in the Gerbil Hippocampus Following Ischaemia: Association with Proliferation of Astrocytes
Authors: Palacios G. , Mengod G. , Tortosa A. , Ferrer I. , Palacios J. M. 
Published: April 2006

AbstractIncreases in β‐amyloid precursor proteins (APP), which include the β‐amyloid senile plaque protein present in patients with Alzheimer's disease, have been shown to occur in models of neuronal damage and neurotoxic cell injury. This observation led us to examine the expression of these proteins after transient ischaemic episodes in the gerbil. Animals were killed 2–28 days after ischaemia and APP were detected by immunocytochemistry at the light and electron microscopic levels with an antibody raised against the C‐terminal region of these proteins. The gliotic reaction was also examined using glial fibrillary acid protein (GFAP) immunoreactivity. Two days after ischaemia, neuronal cell death was observed in the hippocampal CA1 region accompanied by astrocyte hypertrophy. These hypertrophic astrocytes were found to be GFAP positive but stained weakly for APP. Seven days after ischaemia both astrocyte hypertrophic and hyperplasia, with identified mitotic figures, were observed. These hyperplasic astrocytes were intensely stained by the APP antibody, and were observed up to 28 days after ischaemia. This shows that neuronal cell death produced by transient ischaemia is followed by an increased APP expression which appears to be associated with the hyperplasic astrocytes but not with the initial hypertrophy of this cell population. These results, when taken together with those obtained in other models of neuronal damage or death, clearly suggest that APP expression follows neuronal death and is associated with astrocyte proliferation.
Crucial Role for the Myelin‐associated Glycoprotein in the Maintenance of Axon‐Myelin Integrity
Authors: Fruttiger M. , Montag D. , Schachner M. , Martini R. 
Published: April 2006

AbstractIt has recently been shown that mice deficient in the gene for myelin‐associated glycoprotein develop normal myelin sheaths in the peripheral nervous system. Here we report that in mutant mice older than 8 months the maintenance of axon‐myelin units is disturbed, resulting in both axon and myelin degeneration. Morphological features include those typically seen in human peripheral neuropathies, where demyelination‐induced Schwann cell proliferation and remyelination lead to the formation of so‐called onion bulbs. Expression of tenascin‐C, a molecule indicative of peripheral nerve degeneration, was up‐regulated by axon‐deprived Schwann cells and regenerating axons were occasionally seen. Myelin‐associated glycoprotein thus appears to play a crucial role in the long‐term maintenance of the integrity of both myelin and axons.
Basic Fibroblast Growth Factor Opens Calcium‐Permeable Channels in Quail Mesencephalic Neural Crest Neurons
Authors: Distasi Carla , Munaron Luca , Laezza Fernanda , Lovisolo Davide 
Published: April 2006

AbstractIn order to investigate the action of basic fibroblast growth factor (bFGF) in the nervous system, we have studied the ionic signals elicited by this peptide in cultured quail mesencephalic neural crest neurons using patch‐clamp and cytofluorimetric techniques. In this preparation stimulation with bFGF induced, with a delay of some tens of seconds, an inward cationic current. Single‐channel experiments provided evidence for the activation of a calcium‐permeable channel. In single‐cell cytofluorimetric measurements, a sustained rise in [Ca2+Ii was observed, which was dependent on the presence of external calcium. These events may play a role in the developmental effects of bFGF.
Biphasic Expression of the Fos and Jun Families of Transcription Factors Following Transient Forebrain Ischaemia in the Rat. Effect of Hypothermia
Authors: Kamme Fredrik , Campbell Kenneth , Wieloch Tadeusz 
Published: April 2006

AbstractTransient global ischaemia induces the expression of immediate early genes. Using in situ hybridization, the expression of c‐fos, fosB, fra‐1, fra‐2, c‐jun and junB was studied after 15 min of normothermic and hypothermia (33°C) transient forebrain ischaemia in the rat, induced by common carotid occlusion combined with systemic hypotension. Two phases of induction of the immediate early genes were observed. The early phase, peaking at 1–2 h of reperfusion, was dominated by marked expression in the dentate gyrus. The second phase, with maximal expression at 12–36 h of reperfusion, was observed particularly in the vulnerable CA1 and CA3 regions. Hypothermia increased the early induction of one of the genes studied, signifying a differential effect of hypothermia upon the signal transduction mechanisms activating these genes. The late induction occurred earlier after hypothermic than after normothermic ischaemia. The early expression of immediate early genes is due to the rapid activation of cytosolic response elements caused by the ischaemic insult. We suggest that the late induction is a stress signal for activation of repair processes, analogous to the cellular response seen after UV light‐induced DMA damage. The relatively fast induction of the immediate early genes following hypothermic ischaemia may reflect a faster resumption of normal intracellular signalling, enhancing neuronal recovery.
pH‐dependent Facilitation of Synaptic Transmission by Histamine in the CA1 Region of Mouse Hippocampus
Authors: Yanovsky Y. , Reymann K. , Haas H. L. 
Published: April 2006

AbstractThe action of histamine on excitatory synaptic transmission in the CA1 region of the mouse hippocampus was investigated. In a medium at pH 7.4 population spikes were increased for ‐60 min after a brief (5 min) perfusion with histamine (5 μM) but excitatory postsynaptic potentials (EPSPs) were unaffected, as previously reported in the rat. At pH 7.0, however, a late component of extra‐ and intracellularly registered EPSPs was enhanced in two phases: a shorter (by 30%) and a longer lasting one (<1 h by 10%). The NMDA antagonist amino‐phosphonovalerate (60 μM) blocked this late component and prevented the EPSP broadening by histamine. In some cells histamine induced burst‐firing and prolonged EPSPs. The actions on EPSPs were not mediated by any of the known histamine receptors as they were not mimicked by histamine H1, H2 and H3 agonists or blocked by H1, H2 or H3 antagonists. We conclude that histamine enhances a late (NMDA) component of hippocampal EPSPs when protonization is increased by a slight shift of the pH in the acidic direction. Such shifts occur during intense nervous discharges, e.g. in epileptic tissue or following tetanic stimulation, and in hypoxic conditions.
Down‐regulation of Glial Glutamate Transporters after Glutamatergic Denervation in the Rat Brain
Authors: Levy L. M. , Lehre K. P. , Walaas S. I. , Storm‐Mathisen J. , Danbolt N. C. 
Published: April 2006

AbstractMembrane‐localized transporter proteins, expressed in both neurons and glial cells, are responsible for removal of extracellular glutamate in the mammalian CNS. The amounts and activities of these transporters may be under regulatory control. We demonstrate here that cortical lesions, which decrease striatal glutamate uptake in synaptosome‐containing homogenates by ∼50%, also decrease the striatal concentrations of the astrocytic glutamate transporter proteins, GLT‐1 and GLAST by ∼20–30%. Since GABA uptake activity was not decreased and glial fibrillary acidic protein was increased in the same samples, the lesion‐induced losses of GLT‐1 and GLAST were not caused by a general impairment of neuronal or glial function. The observed reduction in the two astrocytic glutamate transporters after corticostriatal nerve terminal degeneration indicates that their levels of expression are dependent on glutamatergic innervation.
Differential Effects of Forebrain 5‐Hydroxytryptamine Depletions on Pavlovian Aversive Conditioning to Discrete and Contextual Stimuli in the Rat
Authors: Wilkinson Lawrence S. , Humby Trevor , Robbins Trevor W. , Everitt Barry J. 
Published: April 2006

AbstractThe experiments examined the effects of depleting forebrain 5‐hydroxytryptamine (5HT) on Pavlovian aversive conditioning to discrete and contextual stimuli. Rats were lesioned with intracerebroventricular injections of the neurotoxin 5,7‐dihydroxytryptamine and then conditioned in a distinctive environment (termed the context) to a 30 s auditory stimulus. In 50% of animals the interval between the offset of the discrete auditory stimulus and the reinforcer, a mild foot‐shock (0.5 mA, 0.5 s), was 5 s (the short‐trace group) and in the other 50%, 30 s (the long‐trace group). Theory predicts that animals in the short‐trace condition will learn more about the discrete stimulus as a predictor of shock and become strongly conditioned, while those in the long‐trace condition learn relatively more about the context. The extent of conditioning to the discrete and contextual stimuli was assessed separately, in extinction, using lick‐suppression and place‐preference measures respectively. Under these conditions sham subjects exhibited the expected dissociation with respect to trace interval. However, lesioned animals exhibited a specific impairment in contextual conditioning. The results are discussed in terms of the behavioural, neurochemical and neuroanatomical specificity of 5HT function in aversive conditioning and the implications for general theories of the role of 5HT in aversive processes.
Expression of NMDA Receptor mRNAs in Rat Motoneurons is Down‐regulated after Axotomy
Authors: Piehl Fredrik , Tabar Gabriella , Cullheim Staffan 
Published: April 2006

AbstractThe cytotoxic effects of glutamate via the N‐methyl‐D‐aspartate (NMDA) receptor have been suggested to take part in the events leading to death of motoneurons after neonatal axotomy. By the use of in situ hybridization and immunohistochemistry we have investigated motoneuron mRNA expression of the NMDA receptor subunits NR1, NR2B and NR2D and of the NR1 subunit protein in two lesion models leading to partial motoneuron death: sciatic nerve transection early postnatally in the rat and ventral root avulsion in the adult rat. The results were compared with a lesion model with no subsequent death of motoneurons, i.e. sciatic nerve transection in the adult rat. All lesions were followed by down‐regulation of the mRNAs for all studied subunits in severed motoneuron populations; down‐regulation was detectable already at early stages postoperatively before any significant death had taken place. The strongest down‐regulation was in fact seen in the lesion with the largest loss of motoneurons (ventral root avulsion). The reduction in the expression of NR1 mRNA was paralleled by a decrease in NR1 subunit protein. We conclude that down‐regulation of NMDA receptor subunit expression is part of the acute response to axonal injury in motoneurons, whether or not neuronal death follows, and that the susceptibility of lesioned motoneurons to excitotoxic effects should be highest early after axonal injury.
A Critical Period for Axon Regrowth Through a Lesion in the Developing Mammalian Retina
Authors: MacLaren R. E. , Taylor J. S. H. 
Published: April 2006

AbstractAlthough the central nervous system of mature mammals is incapable of regeneration, certain elements present in the developing system must permit and promote the growth of new axons to their initial targets. We investigate whether the environment of a developing visual system is capable of supporting regeneration in the Brazilian opossum Monodelphis domestica, in which the retinofugal system develops postnatally. Retinae were lesioned up to the 16th postnatal day and analysed for regeneration after a further 7–10 days. Anterograde tracing with Dil showed axons to have regrown from the axotomized area of retina directly through the lesion. Retrograde tracing with horseradish peroxidase injected into the superior colliculus confirmed that axons from the lesioned area of retina had grown to an appropriate position in the midbrain. The proportion of retinae in which axonal continuity was restored across the lesion decreased as the visual system matured, falling to zero after the 12th postnatal day. Thus a critical period exists in the postnatal opossum in which a retinal lesion permits axon passage. Correlating these results to the known pattern of retinofugal pathway development provides an insight into factors that may restrict this critical period to the 12th postnatal day, and suggests that at least some of the axotomized neurons are regenerating.
Activation of p44 and p42 MAP Kinases is not Essential for the Survival of Rat Sympathetic Neurons
Authors: Virdee Kanwar , Tolkovsky Aviva M. 
Published: April 2006

AbstractWe have examined whether activation of MAP kinases [or extracellular signal‐regulated kinases (ERKs)] is required for the survival of rat sympathetic neurons by comparing the actions of three survival factors whose survival‐promoting actions can be blocked by neutralizing Fab fragments to p21 ras (Nobes and Tolkovsky, 1995, Eur. J. Neurosci., 7, 344–350), nerve growth factor (NGF), the cytokines ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor (LIF), and the cyclic AMP analogue 4‐(8‐chlorophenylthio)cAMP (CPTcAMP). NGF‐induced survival was accompanied by an intense (15‐ to 30‐fold) and steady (>24 h) activation of p44 and p42 ERKs which waned rapidly (t1/2∼30 min) upon NGF withdrawal. However, concentrations of NGF that induced a weak (4‐ to 5‐fold) stimulation of the ERKs were not sufficient to maintain long‐term survival. Moreover, prolonged and intense stimulation of the ERKs by NGF for up to 15.5 h was unable to confer long‐term survival, since withdrawal of NGF after this time resulted in neuronal death that was kinetically indistinguishable from the death of neurons that had not been exposed to NGF. By contrast, CNTF and LIF continued to support survival for up to 3 days after eliciting only transient (<30 min and 1 h respectively) activation of p44 and p42 ERKs, while CPTcAMP induced survival for several days without any measurable activation of the ERKs. Taken together, these data suggest that ERK activation perse is neither necessary nor sufficient for survival and that alternative pathways exist for effecting long‐term survival of rat sympathetic neurons.
Synaptic Input of Horizontal Interneurons in Stratum Oriens of the Hippocampal CA1 Subfield: Structural Basis of Feed‐back Activation
Authors: Blasco‐Ibáñez J. M. , Freund T. F. 
Published: April 2006

AbstractThe synaptic input of interneurons with horizontal dendrites in stratum oriens of the CA1 region was investigated, with particular attention to the portion of synapses originating from local pyramidal cells. Most of these GABAergic interneurons are known to contain somatostatin, and terminate on pyramidal dendrites in conjunction with entorhinal afferents in stratum lacunosum‐moleculare. A smaller number of horizontal cells in this layer are immunoreactive for calbindin, and project to the medial septum. Selective ischaemic degeneration was used to label local axon collaterals of CA1 pyramidal cells, and immunostaining for mGluR1 or calbindin to visualise somatostatin‐ and calbindin‐containing horizontal interneurons, respectively, at the stratum oriens‐alveus border. The number of degenerating and intact synaptic boutons was counted on mGluR1‐ as well as on calbindin‐positive dendrites and somata, whereas in another group of animals the proportion of GABA‐immunoreactive synapses was estimated on calbindin‐positive dendrites. On average, >60% of the total presynaptic elements of both cell types were degenerating, i.e. originated from CA1 pyramidal cells, whereas GABA‐positive boutons, which are known to survive ischaemia, are likely to account for a large proportion of non‐degenerating boutons. Thus the vast majority of presumed excitatory synapses on somatostatin‐ and calbindin‐containing horizontal neurons derives from local collaterals of CA1 pyramidal cells. The remaining GABA‐negative synapses surviving ischaemia may also originate from CA1 pyramidal cells, e.g. from those in the ventral hippocampus, which are rarely damaged by global forebrain ischaemia. Alternative sources may include subcortical afferents known to innervate interneurons, or ipsi‐ and contralateral CAS pyramidal cells, which, according to the present results, may account only for a negligible number of synapses on these interneuron types. We conclude that somatostatin‐containing neurons at the oriens‐alveus border of CA1, which are likely to mediate an inhibitory control of the efficacy and/or plasticity of entorhinal synapses on pyramidal cell dendrites, are driven primarily in a feed‐back manner. The source of afferent excitation for calbindin‐containing horizontal neurons in this region is very similar, suggesting that the GABAergic hippocamposeptal feed‐back is also activated by local pyramidal cell collaterals.
Immunohistochemical Localization of Five Members of the KV1 Channel Subunits: Contrasting Subcellular Locations and Neuron‐specific Co‐localizations in Rat Brain
Authors: Veh Rüdiger W. , Lichtinghagen Ralf , Sewing Sabine , Wunder Frank , Grumbach Isabella M. , Pongs Olaf 
Published: April 2006

AbstractA large variety of potassium channels is involved in regulating integration and transmission of electrical signals in the nervous system. Different types of neurons, therefore, require specific patterns of potassium channel subunit expression and specific regulation of subunit coassembly into heteromultimeric channels, as well as subunit‐specific sorting and segregation. This was investigated by studying in detail the expression of six different α‐subunits of voltage‐gated potassium channels in the rat hippocampus, cerebellum, olfactory bulb and spinal cord, combiningin situhybridization and immunocytochemistry. Specific polyclonal antibodies were prepared for five α‐subunits (KV1.1, KV1.2, KV1.3, KV1.4, KV1.6) of theShaker‐related subfamily of rat Kvchannels, which encode delayed‐rectifier type and rapidly inactivating A‐type potassium channels. Their distribution was compared to that of an A‐type potassium channel (KV3.4), belonging to theShaw‐related subfamily of rat Kvchannels. Our results show that these Kvchannel α‐subunits are differentially expressed in rat brain neurons. We did not observe in various neurons a stereotypical distribution of Kvchannel α‐subunits to dendritic and axonal compartments, but a complex differential subcellular subunit distribution. The different Kvchannel subunits are targeted either to presynaptic or to postsynaptic domains, depending on neuronal cell type. Thus, distinct combinations of Kv1 α‐subunits are co‐localized in different neurons. The implications of these findings are that both differential expression and assembly as well as subcellular targeting of Kvchannel α‐subunits may contribute to Kvchannel diversity and thereby to presynaptic and postsynaptic membrane excitability.
NADPH Diaphorase Expression in the Rat Retina after Axotomy—a Supportive Role for Nitric Oxide?
Authors: Huxlin Krystel R. , Bennett Max R. 
Published: April 2006

AbstractThe large majority of mammalian retinal ganglion cells degenerate following section of their axons in the optic nerve. It has been suggested that some axotomized retinal ganglion cells die because of toxic agents produced within their immediate environment. Our hypothesis was that nitric oxide might be one of the toxic factors implicated in the death of adult retinal ganglion cells post‐axotomy. In the first instance, we determined whether there were any changes in the retinal expression of NADPH diaphorase both 3 and 14 days following intraorbital section of the optic nerve in adult rats. Secondly, if nitric oxide was indeed implicated in the death of ganglion cells, then trophic factors which rescue these neurons might do so by decreasing the expression of nitric oxide synthase. Recently, we found that a collicular proteoglycan purified from the major target of retinal ganglion cells, the superior colliculus, rescued a greater proportion of adult ganglion cells from axotomy‐induced death than most other known trophic factors. We thus injected this proteoglycan intraocularly after section of the optic nerve and examined its effect on the expression of NADPH diaphorase in the retina. Thirdly, an inhibitor of nitric oxide synthetase was repeatedly injected into the eye following the section of the optic nerve in order to determine if such a treatment might improve the survival of retinal ganglion cells. The present results indicate that section of the optic nerve does not alter the overall levels of NADPH diaphorase within the adult rat retina. Intraocular injections of the collicular proteoglycan actually increased the number of neurons expressing NADPH diaphorase, particularly in the ganglion cell layer. Finally, inhibition of nitric oxide synthetase following axotomy resulted in increased loss of retinal ganglion cells over a 2 week period when compared with controls. Our findings indicate that, rather than being toxic, small amounts of nitric oxide may be important for the survival of a proportion of injured retinal ganglion cells.
BC1 RNA and Vasopressin mRNA in Rat Neurohypophysis: Axonal Compartmentalization and Differential Regulation during Dehydration and Rehydration
Authors: Trembleau Alain , Melia Kathleen R. , Bloom Floyd E. 
Published: April 2006

AbstractBrain cytoplasmic 1 (BC1) RNA is a small non‐translated RNA polymerase III transcript. Because this RNA can be detected in the rat posterior pituitary with 35S in situ hybridization autoradiography, it has been hypothesized that this RNA might be transported in the axons of hypothalamo‐neurohypophyseal neurons. In the present study, we aimed to determine the cellular localization of BC1 more precisely by using non‐radioactive in situ hybridization of BC1 RNA at both the light and electron microscopic levels. Our studies revealed that BC1 RNA was indeed located intra‐axonally. Furthermore, BC1 RNA was abundant within a subset of axonal swellings and/or terminals, and was also found in discrete cytoplasmic domains of undilated axonal segments. Using a semiquantitative in situ hybridization approach, we have measured and compared the changes in BC1 RNA and arginine vasopressin (AVP) mRNA during dehydration (chronic salt‐loading) and rehydration. Chronic salt‐loading significantly increased both BC1 RNA and AVP mRNA. The increase in BC1 RNA labelling (2.5‐fold), however, was modest and somewhat less enduring than the increase in AVP mRNA labelling (13‐fold). Upon rehydration, both the BC1 and vasopressin transcripts in the posterior pituitary rapidly returned to control values. In conclusion, like vasopressin mRNA, BC1 RNA is transported in axons of the hypothalamo‐neurohypophyseal system where it aggregates in a subset of axonal swellings, and its axonal transport is similarly regulated. Therefore, we propose that BC1 RNA might be involved in the axonal targeting, docking and/or transport of AVP or other axonal mRNAs.
Lesions of the Superior Temporal Cortical Motion Areas Impair Speed Discrimination in the Macaque Monkey
Authors: Orban Guy A. , Saunders Richard C. , Vandenbussche Erik 
Published: April 2006

AbstractThe effects of circumscribed lesions of the superior temporal cortical motion areas on speed discrimination were tested in three macaque monkeys using both moving random‐textured patterns and moving bars. The lesions, which included the middle temporal visual area, the adjacent medial superior temporal visual area and the fundus superior temporal visual area, produced a severe and lasting deficit in speed discrimination when tested with the random patterns. In contrast, deficits were smaller when tested with moving bars. Control lesions of the inferior temporal cortex in two monkeys had little effect on speed discrimination. There was no clear deficit following inferior temporal or superior temporal sulcus lesions on a vernier acuity task. These experiments indicate that the middle temporal and adjacent areas play a crucial role in speed discrimination and that lesion effects depend on the cues available to the animals.