bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of long‐term treatment with dopamine receptor agonists and antagonists on terminal arbor size
Authors: Parish C. L. , Stanic D. , Drago J. , Borrelli E. , Finkelstein D. I. , Horne M. K. 
Published: March 2003

AbstractThis study demonstrates that pharmacological manipulation of the dopamine (DA) receptors can modulate the size of the axonal tree of substantia nigra pars compacta (SNpc) neurons in mice. Pharmacological blockade or genetic ablation of the D2 receptor (D2R) resulted in sprouting of DA SNpc neurons whereas treatment with a D2 agonist resulted in pruning of the terminal arbor of these neurons. Agents such as cocaine, that indirectly stimulate D2R, also resulted in reduced terminal arbor. Specific D1 agonists or antagonists had no effect on the density of DA terminals in the striatum. We conclude that the D2 receptor has a central role in regulating the size of the terminal arbor of nigrostriatal neurons. These findings have implications relating to the use of dopaminergic agonists in the management of Parkinson's disease and in controlling plasticity following injury, loss or transplantation of DA neurons.
Role of the paraventricular nucleus microenvironment in stress integration*
Authors: Herman James P. , Cullinan William E. , Ziegler Dana R. , Tasker Jeffrey G. 
Published: March 2003

AbstractThe hypothalamic paraventricular nucleus is the primary controller of hypothalamo‐pituitary–adrenocortical glucocorticoid release. In performing this function, the paraventricular nucleus summates a variety of information from both external and internal sources into a net secretory signal to the adrenal cortex. In this review, we will provide an overview of neuronal circuit mechanisms governing activation and inhibition of hypophysiotrophic neurons, highlight recent developments in our understanding of nonsynaptic mechanisms regulating paraventricular cellular activity, including dendritic neuropeptide release, direct steroid feedback, cytokine cascades and gaseous neurotransmission, and illustrate the capacity for hypophysiotrophic, neurohypophysial and preautonomic paraventricular effector pathways to work together in control of glucocorticoid release. The current state of knowledge reveals the paraventricular nucleus to be a dynamic entity, capable of integrating diverse classes of signals into control of adrenocortical activation.
Immune‐related mechanisms participating in resistance and susceptibility to glutamate toxicity
Authors: Schori Hadas , Yoles Eti , Wheeler Larry A. , Raveh Tal , Kimchi Adi , Schwartz Michal 
Published: March 2003

AbstractGlutamate is an essential neurotransmitter in the CNS. However, at abnormally high concentrations it becomes cytotoxic. Recent studies in our laboratory showed that glutamate evokes T cell‐mediated protective mechanisms. The aim of the present study was to examine the nature of the glutamate receptors and signalling pathways that participate in immune protection against glutamate toxicity. We show, using the mouse visual system, that glutamate‐induced toxicity is strain dependent, not only with respect to the amount of neuronal loss it causes, but also in the pathways it activates. In strains that are genetically endowed with the ability to manifest a T cell‐dependent neuroprotective response to glutamate insult, neuronal losses due to glutamate toxicity were relatively small, and treatment with NMDA‐receptor antagonist worsened the outcome of exposure to glutamate. In contrast, in mice devoid of T cell‐dependent endogenous protection, NMDA receptor antagonist reduced the glutamate‐induced neuronal loss. In all strains, blockage of the AMPA/KA receptor was beneficial. Pharmacological (with α2‐adrenoceptor agonist) or molecular intervention (using either mice overexpressing Bcl‐2, or DAP‐kinase knockout mice) protected retinal ganglion cells from glutamate toxicity but not from the toxicity of NMDA. The results suggest that glutamate‐induced neuronal toxicity involves multiple glutamate receptors, the types and relative contributions of which, vary among strains. We suggest that a multifactorial protection, based on an immune mechanism independent of the specific pathway through which glutamate exerts its toxicity, is likely to be a safer, more comprehensive, and hence more effective strategy for neuroprotection. It might suggest that, because of individual differences, the pharmacological use of NMDA‐antagonist for neuroprotective purposes might have an adverse effect, even if the affinity is low.
Two major distinct subpopulations of neurokinin‐3 receptor‐expressing neurons in the superficial dorsal horn of the rat spinal cord
Authors: Ding Yu‐Qiang , Lu Chun‐Rong , Wang Hong , Su Chang‐Jun , Chen Liang‐Wei , Zhang Yuan‐Qiang , Ju Gong 
Published: March 2003

AbstractThis study was designed to provide evidence for elucidating the mechanisms of neurokinin‐3 receptor (NK3) in spinal pain modulation. First, colocalization of NK3 with the µ‐opioid receptor (MOR1) was studied in the spinal dorsal horn of the rat. Confocal microscopy showed that about 44% of NK3‐expressing neurons in laminae I and II were immunoreactive for MOR1, which corresponded to about 93% of the total population of MOR1‐containing neurons in these laminae. Second, the relationship between NK3/MOR1‐coexpressing neurons and those that express nitric oxide synthase (NOS) was examined by using a triple immunofluorescent staining method. About 37% of NK3‐immunoreactive neurons were also NOS‐immunoreactive, which constituted about 82% of NOS‐immunoreacitve neurons in the superficial laminae. However, no triple‐labelled neurons were detected. The present results indicate that there are two major distinct subpopulations of NK3‐expressing neurons in the superficial dorsal horn, which suggests that the involvement of NK3 receptor in spinal nociception could be mediated by two distinct mechanisms, i.e. opioid and nitric oxide.
The antidepressant tianeptine persistently modulates glutamate receptor currents of the hippocampal CA3 commissural associational synapse in chronically stressed rats
Authors: Kole Maarten H. P. , Swan Laura , Fuchs Eberhard 
Published: March 2003

AbstractRecent hypotheses on the action of antidepressants imply a modulation of excitatory amino acid transmission. Here, the effects of long‐term antidepressant application in rats with the drug tianeptine were examined at hippocampal CA3 commissural associational (c/a) glutamate receptor ion channels, employing the whole‐cell patch‐clamp technique. The drug's impact was tested by subjecting rats to daily restraint stress for three weeks in combination with tianeptine treatment (10 mg/kg/day). Whereas stress increased the deactivation time‐constant and amplitude of the N‐methyl‐d‐aspartate (NMDA) receptor‐mediated excitatory postsynaptic currents (EPSCs), it did not affect the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)/kainate receptor‐mediated EPSCs. Concomitant pharmacological treatment of stressed animals with tianeptine resulted in a normalized scaling of the amplitude ratio of NMDA receptor to AMPA/kainate receptor‐mediated currents and prevented the stress‐induced attenuation of NMDA‐EPSCs deactivation. Both paired‐pulse‐facilitation and frequency‐dependent plasticity remained unchanged. Both in control and stressed animals, however, tianeptine treatment strengthened the slope of the input‐output relation of EPSCs. The latter was mimicked by exposing hippocampal slices in vitro with 10 µm tianeptine, which rapidly increased the amplitudes of NMDA‐ and AMPA/kainate EPSCs. The enhancement of EPSCs could be blocked by the intracellular presence of the kinase inhibitor staurosporine (1 µm), suggesting the involvement of a postsynaptic phosphorylation cascade rather then presynaptic release mechanisms at CA3 c/a synapses. These results indicate that tianeptine targets the phosphorylation‐state of glutamate receptors at the CA3 c/a synapse. This novel signal transduction mechanism for tianeptine may provide a mechanistic resolution for its neuroprotective properties and, moreover, a pharmacological trajectory for its memory enhancing and/or antidepressant activity.
Convergence of parvocellular and magnocellular information channels in the primary visual cortex of the macaque
Authors: Vidyasagar T. R. , Kulikowski J. J. , Lipnicki D. M. , Dreher B. 
Published: March 2003

AbstractWe investigated whether responses of single cells in the striate cortex of anaesthetized macaque monkeys exhibit signatures of both parvocellular (P) and magnocellular (M) inputs from the dorsal lateral geniculate nucleus (dLGN). We used a palette of 128 isoluminant hues at four different saturation levels to test responses to chromatic stimuli against a white background. Spectral selectivity with these isoluminant stimuli was taken as an indication of P inputs. The presence of magnocellular inputs to a given cortical cell was deduced from its responses to a battery of tests, including assessment of achromatic contrast sensitivity, relative strengths of chromatic and luminance borders in driving the cell at different velocities and conduction velocity of their retino‐geniculo‐cortical afferents. At least a quarter of the cells in our cortical sample appear to receive convergent P and M inputs. We cannot however, exclude the possibility that some of these cells could be receiving a convergent input from the third parallel channel from the dLGN, namely the koniocellular (K) rather than the P channel. The neurons with convergent P and M inputs were recorded not only from supragranular and infragranular layers but also from the principal geniculate input recipient layer 4. Thus, our results challenge classical ideas of strict parallelism between different information streams at the level of the primate striate cortex.
Role of NMDA receptors and MAP kinase in the amygdala in extinction of fear: clinical implications for exposure therapy*
Authors: Davis Michael 
Published: March 2003

AbstractInfusions into the amygdala (a brain area essential for excitatory fear conditioning) of either NMDA receptor antagonists or inhibitors of the NMDA receptor‐linked mitogen activated protein kinase cascade block extinction learning. Conversely, the NMDA receptor agonist d‐cycloserine facilitates extinction after either systemic administration or intra‐amygdala infusion. Because therapeutic interventions based on extinction procedures are commonly used to treat fear disorders, and because d‐cycloserine is a widely available and safe compound, d‐cycloserine or similar agents might be usefully combined with traditional extinction‐based approaches in the treatment of clinical fear.
Tactile motion activates the human middle temporal/V5 (MT/V5) complex
Authors: Hagen Matthew C. , Franzén Ove , McGlone Francis , Essick Greg , Dancer Christopher , Pardo José V. 
Published: March 2003

AbstractThe human middle temporal/V5 complex (hMT/V5) plays a central role in the perception of visual motion. This region is considered a unimodal visual area with little direct involvement of other sensory modalities. The current study uses H215O PET to test whether tactile motion influences the activity of hMT/V5. Regional cerebral blood flow (rCBF) within hMT/V5 was estimated in eight subjects in separate tactile motion and visual motion conditions, each contrasted with a resting, control. The tactile motion condition involved a brush stroked proximal‐to‐distal along the volar forearm and palm, while the subject attended to the stimulus with closed eyes. The visual motion condition consisted of low contrast, grey‐scale rings radiating at 15°/s from a central point, upon which the subject was instructed to fixate. The location of hMT/V5 was defined for each subject separately as the local maximum of rCBF change during the visual motion condition (vs. control). The average change in rCBF within spherical regions of interest at each peak revealed significant bilateral activation of hMT/V5 in the tactile motion condition contrasted with a second, independent set of control scans. Additionally, a single subject received a sufficient number of scans to perform a pixel‐wise, within‐subject analysis. His functional images were coregistered to his anatomical MRI. In this subject, tactile motion produced a significant increase in rCBF that directly overlapped a region activated by visual motion at the posterior continuance of the inferior temporal sulcus, consistent with the known location of hMT/V5. These results suggest involvement of the hMT/V5 complex in tactile motion processing.
Methamphetamine‐induced, suprachiasmatic nucleus‐independent circadian rhythms of activity and mPer gene expression in the striatum of the mouse
Authors: Iijima Michihiko , Nikaido Takato , Akiyama Masashi , Moriya Takahiro , Shibata Shigenobu 
Published: March 2003

AbstractWhile the suprachiasmatic nucleus (SCN) coordinates the majority of daily rhythms, some circadian patterns of expression are controlled from outside of the SCN. These include responses to daily methamphetamine (MAP) injection, or daily restricted feeding. The mechanisms underlying these SCN‐independent circadian rhythms are unknown. A circadian oscillation in the expression of mPer1 and/or mPer2, mouse period, in the SCN is considered necessary to generate an SCN‐dependent circadian rhythm. Therefore, in this experiment, we examined the association between mPer gene expression and the MAP‐induced, SCN‐independent circadian rhythm. Acute injection of MAP caused an elevation of mPer1, mBmal1, and mNpas2 gene expression in the striatum and mPer1 in the liver. Daily MAP injection at a fixed time for 6 days shifted the rhythmic mPer1 and mPer2 expression in the striatum from a nocturnal to a diurnal rhythm, but failed to affect that in the SCN. Although lesion of the SCN ‘flattened’mPer gene oscillation in the striatum and liver, daily MAP injection caused both behavioural and mPer gene expression rhythms. Daily MAP injection at variable injection intervals (12–36 h) for 6 days, however, failed to produce mPer gene rhythm in the striatum. Daily repeated MAP signals may strengthen the oscillatory force of SCN‐independent circadian behavioural and molecular rhythms. The present results suggest that daily oscillation of mPer genes outside the SCN is closely associated with the regulation of SCN‐independent rhythms. Thus, the present experiment highlights strongly the important role of clock gene expression, in the brain, that underlies the circadian behavioural rhythm.
Lack of PSD‐95 drives hippocampal neuronal cell death through activation of an αCaMKII transduction pathway
Authors: Gardoni Fabrizio , Bellone Camilla , Viviani Barbara , Marinovich Marina , Meli Elena , Pellegrini‐Giampietro Domenico E. , Cattabeni Flaminio , Di Luca Monica 
Published: March 2003

AbstractThe PSD‐95 protein family organizes the glutamatergic postsynaptic density and it is involved in the regulation of the excitatory signal at central nervous system synapses. We show here that PSD‐95 deficiency by means of antisense oligonucleotides induces significant neuronal cell death within 24 h both in primary hippocampal cultures and in organotypic hippocampal slices. On the other hand, cultured cortical neurons are spared by PSD‐95 antisense toxicity until they reach a NR2A detectable protein level (24 days in vitro). The neurotoxic event is characterized by increased αCaMKII association to NR2 regulatory subunits of NMDA receptor complex. As a direct consequence of αCaMKII association, we found increased GluR1 delivery to cell surface in cultured hippocampal neurons paralleled by AMPA‐dependent increase in [Na+]I levels. In addition, both CaMKII specific inhibitor KN‐93 and AMPA receptor antagonists CNQX and NBQX rescued neuronal survival to control values. On the other hand, both the NMDA channel blocker MK‐801 and Dantrolene, an inhibitor of calcium release from ryanodine‐sensitive endoplasmic reticulum stores, failed to have any effect on neuronal survival in PSD‐95 deficient neurons. Thus, our data provide clues that PSD‐95 reduced expression in neurons is responsible for neuronal vulnerability mediated by direct activation of αCaMKII transduction pathway in the postsynaptic compartment.
Differential sensitivity of sodium channels from the central and peripheral nervous system to the scorpion toxins Lqh‐2 and Lqh‐3
Authors:   Haijun Chen,, Lu SongQing , Leipold Enrico , Gordon Dalia , Hansel Alfred , Heinemann Stefan H. 
Published: March 2003

AbstractThe scorpion α‐toxins Lqh‐2 and Lqh‐3, isolated from the venom of the Israeli yellow scorpion Leiurus quinquestriatus hebraeus, were previously shown to be very potent in removing fast inactivation of rat skeletal muscle sodium channels (Chen et al., 2000). Here, we show that tetrodotoxin‐sensitive neuronal channels NaV1.2 and NaV1.7, which are mainly expressed in mammalian central and peripheral nervous systems, respectively, are differentially sensitive to these two toxins. rNaV1.2 and hNaV1.7 channels were studied with patch‐clamp methods upon expression in mammalian cells. While Lqh‐3 was about 100‐times more potent in removing inactivation in hNaV1.7 channels compared with rNaV1.2, Lqh‐2 was about 20‐times more active in the other direction. Site‐directed mutagenesis showed that the differences in the putative binding sites for these toxins, the S3‐4 linkers of domain 4, are of major importance for Lqh‐3, but not for Lqh‐2.
Persistent epileptiform activity induced by low Mg2+ in intact immature brain structures
Authors: Quilichini P. P. , Diabira D. , Chiron C. , Ben‐Ari Y. , Gozlan H. 
Published: March 2003

AbstractWe have determined the properties of seizures induced in vitro during the first postnatal days using intact rat cortico‐hippocampal formations (CHFs) and extracellular recordings. Two main patterns of activity were generated by nominally Mg2+‐free ACSF in hippocampal and cortical regions: ictal‐like events (ILEs) and late recurrent interictal discharges (LRDs). They were elicited at distinct developmental periods and displayed different pharmacological properties. ILEs were first observed in P1 CHFs 52 ± 7 min after application of low‐Mg2+ ACSF (frequency 1.5 ± 0.3 h‐1, duration 86 ± 3 s). There is a progressive age‐dependent maturation of ILEs characterized by a decrease in their onset and an increase in their frequency and duration. ILEs were abolished by d‐APV and Mg2+ ions. From P7, ILEs were followed by LRDs that appeared 89 ± 8 min after application of low‐Mg2+ ACSF (frequency ≈ 1 Hz, duration 0.66 s, amplitude 0.31 ± 0.03 mV). LRDs were no longer sensitive to d‐APV or Mg2+ ions and persisted for at least 24 h in low‐Mg2+ or in normal ACSF. ILEs and LRDs were synchronized in limbic and cortical regions with 10–40 ms latency between the onsets of seizures. Using a double chamber that enables independent superfusion of two interconnected CHFs, we report that ILEs and LRDs generated in one CHF propagated readily to the other one that was being kept in ACSF. Therefore, at a critical period of brain development, recurrent seizures induce a permanent form of hyperactivity in intact brain structures and this preparation provides a unique opportunity to study the consequences of seizures at early developmental stages.
Insulin‐induced hypoglycemia decreases single‐unit activity of serotonergic medullary raphe neurons in freely moving cats: relationship to sympathetic and motor output
Authors: Martín‐Cora Francisco J. , Fornal Casimir A. , Metzler Christine W. , Jacobs Barry L. 
Published: March 2003

AbstractSerotonergic single‐unit activity during glucoregulatory challenges was studied in the nuclei raphe obscurus (NRO) and raphe pallidus (NRP) of freely moving cats. Systemic insulin administration (2–4 IU/kg, i.v.) suppressed neuronal activity by ≈ 40% in direct relationship to blood glucose levels and in inverse relationship to plasma catecholamine levels. NRO and NRP serotonergic neurons displayed a temporary recovery in unit activity in response to i.v. glucose administration (500 mg/kg), which temporarily reversed insulin‐induced hypoglycemia. The neuronal responses to insulin and subsequent glucose administration were also directly related to changes in integrated nuchal electromyographic activity. Serotonergic unit activity remained unchanged after glucose loading (500 mg/kg, i.v.), which produced a four‐fold increase in blood glucose. Thus, medullary serotonergic neurons appear to be sensitive to reductions, but not increases, in blood glucose. The observed inverse relationship between unit activity and plasma catecholamines does not support a postulated sympathoexcitatory role for these neurons. Instead, the parallel changes in single‐unit activity and integrated muscle activity support the hypothesis that the activity of medullary serotonergic neurons is linked to motor output. These neurons may modulate autonomic outflow, but only in relationship to their primary role in motor control. Finally, medullary serotonergic neurons may play a protective role in maintaining glucose homeostasis by disfacilitating the output of the somatomotor system, and hence diminishing muscle energy demands, when peripheral glucose availability is low.
Sleep deprivation modulates brain mRNAs encoding genes of glycogen metabolism
Authors: Petit Jean‐Marie , Tobler Irene , Allaman Igor , Borbély Alexander A. , Magistretti Pierre J. 
Published: March 2003

AbstractReplenishment of brain glycogen stores depleted during waking has been suggested to constitute one of the functions of sleep [Benington, J. H. & Heller H. C. (1995) Prog. Neurobiol., 45, 347]. We have tested the hypothesis that the level of expression of enzymes involved in glycogen metabolism could undergo variations throughout the sleep‐waking or rest‐activity cycle, and after 6 h of ‘gentle’ total sleep deprivation in mice. Specifically, we determined the variations in mRNAs coding for protein targeting to glycogen (PTG), glycogen synthase and glycogen phosphorylase, all considered as key regulators of glycogen metabolism. Glycogen synthase and glycogen phosphorylase mRNAs exhibited significant variations throughout the light‐dark cycle with a maximum at the middle of the light period and a minimum at the middle of the dark period. Following sleep deprivation, a two‐fold increase in PTG mRNA and a decrease of mRNAs encoding glycogen synthase and glycogen phosphorylase were observed. These transcriptional events have functional consequences as the activity of glycogen synthase was increased 2.5‐fold indicating a stimulating effect of sleep deprivation on glycogen synthesis. These results indicate that (i) expression of genes related to brain glycogen metabolism exhibit variations throughout the sleep‐waking or rest‐activity cycle and (ii) given the almost selective localization of glycogen to astrocytes, these cells might participate in the regulation of sleep.