bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre‐exposure to Subtoxic Levels Prevents Kainic Acid Lesions in Organotypic Hippocampal Slice Cultures: Effects of Kainic Acid on Parvalbumin‐immunoreactive Neurons and Expression of Heat Shock Protein 72 Following the Induction of Tolerance
Authors: Best N. , Sundström L. E. , Mitchell J. , Wheal H. V. 
Published: April 2006

AbstractThe effects of kainic acid on the survival of principal neurons and parvalbumin‐immunoreactive (PARV‐IR) neurons, and on the expression of heat shock protein 72 immunoreactivity (HSP72‐IR) were investigated in organotypic hippocampal slice cultures. Untreated cultures displayed an organotypic organization and the development and morphology of PARV‐IR neurons in the hippocampus paralleled that reported to occur in vivo, with the exception of the hilar region of the dentate gyrus which exhibited a marked lack of PARV‐IR neurons. No constitutive expression of HSP72 was found in untreated cultures. The lesion of CA3 neurons and the reduction in numbers of PARV‐IR neurons in both CA3 and CA1 after chronic exposure to 5 μM kainic acid were similar to those reported to occur in vivo. Exposure to 1 μM doses of kainic acid resulted in a widespread appearance of HSP72‐IR and the induction of tolerance to a previously toxic dose of kainic acid. These results suggest the presence of endogenous neuroprotective mechanisms, activated by a stress response which induces HSP72, and is reminiscent of the induced tolerance reported to occur after a mild ischaemic insult.
BDN F Down‐regulates Neurotrophin Responsiveness, TrkB Protein and TrkB mRNA Levels in Cultured Rat Hippocampal Neurons
Authors: Frank Lone , Ventimiglia Roseann , Anderson Keith , Lindsay Ronald M. , Rudge John S. 
Published: April 2006

AbstractRegulation of Trk receptors by their ligands, the neurotrophins, was investigated in dissociated cultures of embryonic day 18 rat hippocampal neurons. Cultures were exposed to brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3) or NT‐4/5 for 24 h upon plating followed by factor washout. As determined by immunohistochemical staining and phosphotyrosine blotting, the functional responses to acute stimulation with BDNF, NT‐3 and NT‐4/5, including c‐Fos induction and phosphorylation of Trk and extracellular signal‐regulated kinase (ERK) proteins, were significantly decreased after 6 days in culture by prior exposure to BDNF. As determined by Western and Northern blot analysis respectively, there was a parallel down‐regulation of TrkB protein as well as of trkB and trkC mRNA levels in BDNF‐pretreated cultures. Exposure to NT‐3 or NT‐4/5 at the same concentrations as BDNF did not down‐regulate any of the measured cellular responses or TrkB protein and/or trkB and trkC mRNA levels. Regulation of hippocampal neuronal TrkB protein does not appear to be just a developmental phenomenon, as infusion of BDNF into the hippocampus of adult rats for 6 days produced an 80% decrease in levels of full‐length TrkB protein. We thus show that exposure of hippocampal neurons to BDNF, both in culture and in the adult brain, results in down‐regulation of TrkB. At least in vitro, this leads to long‐term functional desensitization to BDNF. NT‐3 and NT‐4/5. as well as down‐regulation of trkB and trkC mRNA.
Lemniscal Input to Identified Neurons of the Central Nucleus of Mouse Inferior Colliculus: an Intracellular Brain Slice Study
Authors: Wagner Thomas 
Published: April 2006

AbstractIntracellular recordings were performed in 34 neurons in the central nucleus of the inferior colliculus in brain slice preparations of the mouse. Sixteen neurons recorded were stained intracellularly by injection of biocytin and identified as multipolar. After electrical stimulation of the lateral lemniscus, 32 of 34 neurons exhibited postsynaptic potentials (PSPs). Onset latencies of the PSPs were 5.0±2.8 ms (range 2‐12 ms), presumably reflecting the lack of a significant monosynaptic input to most of the neurons recorded. An excitatory PSP (EPSP), often followed by a late inhibitory PSP (IPSP), was present in all neurons which received synaptic input. The IPSPs usually had a reversal potential positive to the cell's resting membrane potential, thus working as shunting inhibitors. Superfusion of the slice with the GABAA antagonist bicuculline resulted in blockade of the IPSP and pronounced prolongation of the EPSP. In 50% of these cases, paroxysmal depolarizing shifts were observed in the presence of bicuculline. Blocking the non‐NMDA glutamate receptors with 6,7‐dinitroquinoxaline‐2,3‐dione resulted not only in the total disappearance of EPSPs but also of late IPSPs, indicating that the latter depend on the glutamatergic EPSPs. Furthermore, all neurons recorded must receive substantial innervation from sources within the inferior colliculus, together constituting a complex neuronal network in the inferior colliculus with an important role of the inhibitory neurotransmitter GABA in controlling network properties.
GAP‐43 mRNA in Mouse Motoneurons Undergoing Axonal Sprouting in Response to Muscle Paralysis or Partial Denervation
Authors: Bisby M. A. , Tetzlaff W. , Brown M. C. 
Published: April 2006

AbstractTo test the hypothesis that collateral sprouting of motoneurons can occur without the intervention of metabolic changes in the cell body, we examined the levels of growth‐associated protein 43 (GAP‐43) mRNA in mouse motoneurons induced to sprout by muscle inactivity (following marcaine or botulinum toxin treatment) or by partial denervation. GAP‐43 mRNA was selected as an appropriate marker for cell body metabolic changes because it is expressed at low levels in mature motoneurons, but is strongly expressed during developmental or regenerative axonal growth in motoneurons. Sprouting motoneurons were identified by retrograde labelling with fluorescent tracers applied to the muscle in which sprouting occurred. Both a full‐length cDNA probe and an oligonucleotide probe were used for in situ hybridization. We were unable to detect any significant increases in GAP‐43 mRNA levels in fluorescent motoneurons after any treatment, except 4 days after partial denervation (but not at 2 or 8 days). This amounted to a 1.6‐fold increase in signal level compared to control motoneurons, while presumed axotomized motoneurons in the same spinal cords displayed on average an 8.7‐fold increase. We conclude that collateral sprouting can occur in motoneurons without a detectable increase in cell body levels of GAP‐43 mRNA. The modest increase observed in the 4‐day partial denervation situation may be a response to the more vigorous and extensive nodal axonal sprouting occurring in these motoneurons. Our results do not deny a role for pre‐existing GAP‐43 in collateral sprouting, but support the hypothesis that sprouting can occur in motoneurons without necessarily requiring increased GAP‐43 mRNA levels in the cell body.
The Extraneuronal Transporter for Monoamine Transmitters Exists in Cells Derived from Human Central Nervous System Glia
Authors: Russ Hermann , Staudt Kerstin , Martel Fátima , Gliese Martin , Schömig Edgar 
Published: April 2006

AbstractFrom studies on sympathetically innervated peripheral tissues it is well known that both neuronal and nonneuronal transport systems contribute to the inactivation of released monoamine transmitters. The close proximity between synapses and glia cell processes in the CNS leads to the so far unresolved question whether non‐neuronal transporters are involved in the inactivation of centrally released monoamine transmitters such as noradrenaline, dopamine and 5‐hydroxytryptamine. 1‐Methyl‐4‐phenylpyridinium (MPP+) is a prototypical substrate of the extraneuronal monoamine transporter (uptake2). [3H]MPP+ was found to accumulate in various human glioma cell lines. [3H]MPP+transport was characterized in more detail in HTZ146 human glioma cells. The Ki values of various compounds for the inhibition of initial rates of [3H]MPP+ transport into HTZ146 cells were closely correlated with the known Ki values for the inhibition of the extraneuronal monoamine transporter (P < 0.001, r= 0.991, n= 7). The rank order of inhibitory potencies was decynium 22 > corticosterone > cyanine 863 > O‐methylisoprenaline > quinine > clonidine > quinidine. [3H]MPP+ accumulation was investigated not only in various CNS tumour cell lines but also in primary cultures of human astrocytes and rat cerebral cortex slices. In all tested experimental systems, accumulation was sensitive to cyanine‐related inhibitors of the extraneuronal monoamine transporter. These findings suggest that the extraneuronal monoamine transporter exists in glia cells. Furthermore, it was shown that MPP+ is able to make use of the extraneuronal monoamine transporter not only to enter but also to leave glia cells. This finding suggests that the extraneuronal monoamine transporter may play a key role in the mechanism of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) neurotoxicity.
Diversity of Postsynaptic Amplitude and Failure Probability of Unitary Excitatory Synapses between CA3 and CA1 Cells in the Rat Hippocampus
Authors: Raastad Morten , Lipowski Rupert 
Published: April 2006

AbstractDifferent CA3 cells may have dissimilar effects on a CA1 pyramidal cell. In order to test this idea, we studied the amplitude distribution of excitatory postsynaptic currents (EPSCs) in response to weak electrical stimulation of presynaptic axons in the rat hippocampal slice. We accepted the response populations as representative for the effect of, in most cases, a single axon when the EPSCs appeared at a certain threshold stimulation strength, with the subsequent lack of increase in amplitude with further stimulation increase. By comparing the EPSC amplitude distributions obtained from different synaptic inputs to the same CA1 cell, we found differences in the failure probability and the EPSC amplitude, each of which contributed to differences in the mean response amplitude. We conclude that not only the number but also the specific subset of active CA3 cells is important for the synaptically driven discharge of a given CA1 cell.
Noradrenalin Enhances the Activity of Cochlear Nucleus Neurons in the Rat
Authors: Ebert Ulrich 
Published: April 2006

AbstractThe cochlear nucleus of rats is heavily innervated by noradrenergic fibres from the locus coeruleus. The physiological meaning of this innervation is poorly understood. Therefore, iontophoretically applied noradrenalin was tested on single neurons of the cochlear nucleus in urethane‐anaesthetized rats. Iontophoresis of noradrenalin had a dual effect. During application noradrenalin led to moderate inhibition of tone‐evoked activity in 37% of the tested neurons. In contrast, ∼20‐30 s after the onset of iontophoresis a long‐lasting increase in discharge activity was found in most neurons. Data from iontophoresis of the α1‐receptor agonist phenylephrine and the α2‐receptor agonist clonidine suggest that the fast moderate inhibition is mediated by α2‐receptors while the pronounced long‐lasting elevated neuronal firing is mediated by α1‐receptors. However, these data do not exclude the possibility that part of the response to noradrenalin is also mediated by β‐receptors. Electrical stimulation of the locus coeruleus resulted in an increase in discharge activity comparable with iontophoresis of noradrenalin or phenylephrine. Thus, activation of the locus coeruleus predominantly increases spontaneous and tone‐evoked neuronal firing in the cochlear nucleus of the rat. This α1‐receptor‐mediated enhanced discharge activity may serve to increase the sensitivity of acoustic processing mechanisms or to lower the threshold for short‐latency acoustic reflexes.
Effect of Neonatal Axoplasmic Transport Attenuation in the Infraorbital Nerve on Vibrissae‐related Patterns in the Rat's Brainstem, Thalamus and Cortex
Authors: Chiaia Nicolas L. , Bennett‐Clarke Carol A. , Crissman Robert S. , Zheng Li , Chen Min , Rhoades Robert W. 
Published: April 2006

AbstractThis study evaluated the effects of neonatal attenuation of axoplasmic transport in the infraorbital nerve (ION) on the organization of vibrissae‐related patterns in the rat's CNS. Application of colchicine‐ or vinblastine impregnated implants to the ION from birth until postnatal day (P)6 to P10 resulted in a 92.4% reduction in the number of trigeminal (V) ganglion cells labelled by application of horseradish peroxidase to the vibrissa pad and a 44.8% decrease in the number of Nissl‐stained ganglion cells in the ophthalamic‐maxillary portion of the V ganglion. These implants also decreased the number of myelinated fibres in the ION. In normal rats killed on P6‐10, there was an average of 10 273±1259 myelinated axons in the nerve. In the animals with colchicine‐ or vinblastine‐treated implants, this value was 3891±1965. The highest axon count in an experimental animal was 9859. In all animals, axoplasmic transport attenuation resulted in the disappearance of normal vibrissae‐related cytochrome oxidase patterns in the brainstem, thalamus and primary somatosensory cortex. Axoplasmic transport attenuation did not result in the disappearance of vibrissae‐related ordering of V primary afferent terminal arbors, as demonstrated by anterograde labelling with neurobiotin. These results suggest that some factor conveyed from the periphery of the V ganglion and perhaps on to the brainstem is necessary for the maintenance of vibrissae‐related patterns in the thalamus and cortex.
Structural Features of a Close Homologue of L1 (CHL1)in the Mouse: A New Member of the L1 Family of Neural Recognition Molecules
Authors: Holm Jürgen , Hillenbrand Rainer , Steuber Volker , Bartsch Udo , Moos Marion , Lübbert Hermann , Montag Dirk , Schachner Melitta 
Published: April 2006

AbstractWe have identified a close homologue of L1 (CHL1) in the mouse. CHL1 comprises an N‐terminal signal sequence, six immunoglobulin (Ig)‐like domains, 4.5 fibronectin type III (FN)‐like repeats, a transmembrane domain and a C‐terminal, most likely intracellular domain of ˜100 amino acids. CHL1 is most similar in its extracellular domain to chicken Ng‐CAM (˜40% amino acid identity), followed by mouse L1, chicken neurofascin, chicken Nr‐CAM, Drosophila neuroglian and zebrafish L1.l (37‐28% amino acid identity), and mouse F3, rat TAG‐1 and rat BIG‐1 (˜27% amino acid identity). The similarity with other members of the Ig superfamily [e.g. neural cell adhesion molecule (N‐CAM), DCC, HLAR, rse] is 16‐11%. The intracellular domain is most similar to mouse and chicken Nr‐CAM, mouse and rat neurofascin (˜60% amino acid identity) followed by chicken neurofascin and Ng‐CAM, Drosophila neuroglian and zebrafish L1.l and L1.2 (˜40% amino acid identity). Besides the high overall homology and conserved modular structure among previously recognized members of the L1 family (mouse/human L1/rat NILE; chicken Ng‐CAM; chicken/mouse Nr‐CAM; Drosphila neuroglian; zebrafish L1.l and L1.2; chicken/mouse neurofascin/rat ankyrin‐binding glycoprotein), criteria characteristic of L1 were identified with regard to the number of amino acids between positions of conserved amino acid residues defining distances within and between two adjacent Ig‐like domains and FN‐like repeats. These show a collinearity in the six Ig‐like domains and four adjacent FN‐like repeats that is remarkably conserved between L1 and molecules containing these modules (designated the L1 family cassette), including the GPI‐linked forms of the F3 subgroup (mouse F3/chicken F1l/human CNTN1; rat BIG‐l/mouse PANG; rat TAG‐l/mouse TAX‐l/chicken axonin‐1). The colorectal cancer molecule (DCC), previously introduced as an N‐CAM‐like molecule, conforms to the L1 family cassette. Other structural features of CHL l shared between members of the L1 family are a high degree of N‐glycosidically linked carbohydrates (˜20% of its molecular mass), which include the HNK‐1 carbohydrate structure, and a pattern of protein fragments comprising a major 185 kDa band and smaller fragments of 165 and 125 kDa. As for the other L1 family members, predominant expression of CHL l is observed in the nervous system and at later developmental stages. In the central nervous system CHL l is expressed by neurons, but, in contrast to L1, also by glial cells. Our findings suggest a common ancestral L1‐like molecule which evolved via gene duplication to generate a diversity of structurally and functionally distinct yet similar molecules.
Development of Trigeminal Nucleus Principalis in the Rat: Effects of Target Removal at Birth
Authors: Jacquin Mark F. , Rana Jamil Z. , Miller Michael W. , Chiaia Nicolas L. , Rhoades Robert W. 
Published: April 2006

AbstractLittle is known about how neurons develop in the trigeminal nucleus principalis (PrV) despite their acknowledged role in establishing whisker‐related patterns in the thalamus and cortex. Golgi‐impregnated PrV cells were studied in newborn, 4‐day‐old and adult rats. Adult neurons typically had short dendrites that were confined to a hemisphere around the soma. In contrast, at birth PrV neurons had radial trees and more primary dendrites than did adults, but adult‐like numbers of dendritic spines. By day 4, most neurons had eccentric dendritic trees and the numbers of primary dendrites per neuron were adult‐like, yet spines were more prevalent than in adults and newborns. Thus, it appears that there is a pruning of the dendritic tree during the first postnatal week. To assess the role of retrograde signals from the thalamus on PrV development, the right thalamus was destroyed at birth. By postnatal day 6, the number of neurons in the left PrV was 59% of that in the right PrV, PrV transverse area was reduced by 21%, cell density was reduced by 48%, and somatic diameter was increased by 36%, relative to the intact right PrV. By contrast, in the left V subnucleus interpolaris, which has only a weak thalamic projection, these measures were unaffected. Thus, neonatal thalamic lesions selectively depopulated the PrV. The morphology of PrV neurons was affected by the thalamic lesions: e.g. the total dendritic length, the number of dendritic branch points and the total number of spines were increased. The number of primary dendrites and the tree's eccentricity, area, and volume of influence were unaffected by the lesion. The structure of neurons in subnucleus interpolaris was unaffected by the lesion. Thus, normal afferent patterning is insufficient for normal development of PrV cells. Interactions among dendrites and retrograde signals from a target are also important.
Serotonin Regulates Gap Junction Coupling in the Developing Rat Somatosensory Cortex
Authors: Rörig Birgit , Sutor Bernd 
Published: April 2006

AbstractTo further elucidate the role of the neuromodulatory transmitter serotonin (5‐HT) during early postnatal development of the neocortex, we investigated the effects of 5‐HT on gap junction coupling in the somatosensory cortex of rats aged between postnatal days 7 and 10. The gap junction‐permeable tracer neurobiotin was injected into single neurons via microelectrodes or patch pipettes. Under control conditions, clusters of about 25 tracer‐coupled neurons were observed. Serotonin reduced dye‐coupling between lamina II/III pyramidal cells in a concentration‐dependent and reversible manner. The 1,4,5‐inositol triphosphate (IP3) receptor antagonist heparin as well as the protein kinase C inhibitor NPC 15437 suppressed the uncoupling action of 5‐HT, suggesting that the serotonergic effect involved IP3 receptor‐mediated release of calcium ions from intracellular stores. In contrast, the 5‐HT‐induced reduction in gap junction coupling was not antagonized by Rp‐adenosine3′,5′‐cyclic monophosphothionate, an inhibitor of CAMP dependent protein kinase. The uncoupling effect of 5‐HT was mimicked by 5‐HT2 receptor agonists and antagonized by the 5‐HT2 receptor antagonist ritanserin, indicating that 5‐HT suppressed gap junction coupling via activation of 5‐HT2 class receptors. Our results suggest that the developmental functions of 5‐HT not only involve the modulation of chemical synaptic transmission but also include the regulation of the gap junctional communication system during differentiation of the neocortex.
Spontaneous Behaviours of Rats are Differentially Affected by Substantia Nigra Infusions of Brain‐derived Neurotrophic Factor and Neurotrophin‐3
Authors: Martin‐Iverson Mathew T. , Altar C. Anthony 
Published: April 2006

AbstractThe effects on spontaneous behaviour after 7 and 14 days of continuous unilateral infusion of brain‐derived neurotrophic factor (BDNF, 12 μg/day) and neurotrophin‐3 (NT‐3, 12 μg/day) into the rat substantia nigra were investigated during the day and night. Animals subjected to these treatments were compared to untreated controls and vehicle‐infused controls that were weight‐matched for the decreases in body weight produced by BDNF and NT‐3. BDNF increased feeding and food retrieval, indicating that BDNF did not decrease appetite. BDNF but not NT‐3 markedly decreased drinking, suggesting that weight loss in BDNF‐treated rats may be secondary to hypodypsia, whereas in NT‐3‐treated rats weight loss was more likely a direct consequence of decreased feeding. Exploratory behaviours, limb flicks and contralateral postural bias were increased by BDNF. The behavioural profile of BDNF‐treated rats is consistent with an increase in dopaminergic activity. In addition, BDNF increased backwards walking, a behaviour that requires the activation of both dopamine and serotonin systems. In contrast, NT‐3 selectively increased behaviours that are mediated primarily by serotonin, such as wet‐dog shakes. NT‐3 increased limb flicks and mouth movements, but had a smaller effect than BDNF on exploratory behaviour. Vehicle infusions produced behavioural effects consistent with cannula‐ or infusioninduced damage to the nigrostriatal dopamine system, and some of these effects were reversed by BDNF. Most of the behavioural effects of the neurotrophins are consistent with the view that BDNF increases activity of both dopaminergic and serotonergic systems within the nigrostriatal system, and that NT‐3 increases serotonin activity. Effects of BDNF and NT‐3 on grooming behaviours, possibly indicative of actions on nigral neuropeptides, provide further evidence of consistencies between reported neurochemical and behavioural effects of neurotrophins.
Bilateral 6‐Hydroxydopamine‐induced Lesion of the Nigrostriatal Dopamine Pathway Reproduces the Effects of Unilateral Lesion on Substance P but not on Enkephalin Expression in Rat Basal Ganglia
Authors: Salin* Pascal , Hajji Moulay Driss , Goff Lydia Kerkerian‐le 
Published: April 2006

AbstractThis study compared the effects of unilateral and bilateral 6‐hydroxydopamine‐induced lesions of the nigrostriatal dopaminergic neurons on substance P and enkephalin expression in the rat striatum and its main target structures by means of quantitative in situ hybridization and immunocytochemistry. In animals with bilateral lesion, substance P mRNA levels were decreased in the striatum, and this was matched by parallel reductions in substance P immunoreactivity in the striatum and in the striatonigral terminals at substantia nigra level in both hemispheres. These changes were similar to those observed ipsilaterally to unilateral lesion. In contrast, whereas increased striatal enkephalin immunoreactivity and mRNA levels and decreased immunoreactivity in the globus pallidus were observed on the lesioned side after unilateral lesion, no significant change in these enkephalin markers occurred in animals with bilateral lesion. These data suggest that the effects of dopamine deafferentation on substance P expression in the striatonigral system may be due primarily to removal of direct dopamine influence, whereas the effects on enkephalin expression in the striatopallidal system may involve complex interhemispheric adaptive mechanisms. The present finding that bilateral dopamine lesion does not simply reproduce the effects of unilateral lesion but creates a new functional state may have a critical bearing on the understanding and treatment of Parkinson's disease.